Hey there, curious minds! Want to know what’s buzzing in the world of GPCRs? Join us for this week’s update, where you’ll find all the latest breakthroughs and exciting developments in GPCR research. We can’t wait to share it with you! This Week’s Highlights: Harnessing Deep Mutational Scanning for Enhanced Drug Discovery Cam Sinh Lu GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states Fan Liu , Han Zhou , Xiaonong Li , Liangliang Zhou , Chungong Yu , Haicang Zhang , Dongbo Bu 🤩 Seriously, why would you want to miss out on all the awesomeness that comes with a DrGPCR Premium Membership ? 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Classified GPCR News  Let’s dive into the   Classified GPCR News from November 4th to 10th, 2024 Industry News Lexaria Updates Fast-Moving GLP-1 'Arm's Race' Developments Five protein-design questions that still challenge AI Prix Galien USA: Domain Therapeutics Nominated for the Prestigious Best Startup Award Tectonic Therapeutic Announces Positive Phase 1a Results in AHA 2024 Presentation for TX45, a Long-acting, Fc-Relaxin Fusion Protein Nxera Pharma and Antiverse partner on GPCRs Nxera Pharma’s Partner Centessa Initiates Phase 2 Trial with ORX750, a Novel Orexin Receptor 2 (OX2R) Agonist AI, Synthetic Biology and Drug Discovery- with Aikium's Dr Venkatesh Mysore Trevena teeters in dangerous territory, terminating CEO and other execs amid strategic review Trevena Reports Third Quarter 2024 Results and Provides Business Update GPCR Events, Meetings, and Webinars NEW November 18 - 20, 2024 | 7th CB1 & CB2 Targeting Drug Development Summit November 25 - 26, 2024 | 6th International Conference on Stem Cell, Tissue Engineering and Regenerat November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe December 10 - 12, 2024 | Pharmacology 2024 January 13 - 16, 2025 | PepTalk 2025 January 25 - 29, 2025 | SLAS 2025 February 15 - 16, 2025 | Structural and Functional Approaches in GPCR Drug Discovery February 15 - 19, 2025 | BPS 2025 February 16 - 21, 2025 | Harnessing the Power of Advanced Multimodal Approaches to GPCR Drug Discovery March 12 - 14, 2025 | NextGen Biomed 2025 March 25 - 28, 2025 | 10th German Pharm-Tox Summit April 1 - 5, 2025 | XXIII GEM Meeting in 2025 April 3 - 6, 2025 | ASPET 2025 April 14 - 17, 2025 | 20th Drug Discovery Chemistry April 24 - 27, 2025 | American Physiology Summit 2025 April 25 - 30, 2025 | AACR Annual Meeting 2025 May 12 - 15, 2025 | PEGS 2025 May 20 - 22, 2025 | SLAS Europe 2025 June 16 - 19, 2025 | BIO International Convention 2025 July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Scientist I Cell Biology - Tectonic Therapeutic NEW Senior Principal Scientist, Medicinal Chemistry PhD fellowship in GPCR mechanosensing Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry GPCR Activation and Signaling Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel Smad transcription factors as mediators of 7 transmembrane G protein-coupled receptor signalling The voltage sensitivity of G-protein coupled receptors: Unraveling molecular mechanisms and physiological implications Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling GPCR Binders, Drugs, and more PGE2 Binding Affinity of Hemocyte Membrane Preparations of Manduca sexta and Identification of the Receptor-Associated G Proteins in Two Lepidopteran Species GPCRs in Neuroscience Role of the GRK2/3 N-terminus in discriminating the endocytic effects of opioid agonist drugs GPCRs in Oncology and Immunology GPR56: GPCR as a guardian against ferroptosis Methods & Updates in GPCR Research Memprot.GPCR-ModSim: Modelling and simulation of membrane proteins in a nutshell Ciliary length variations impact cilia-mediated signaling and biological responses Structural and Molecular Insights into GPCR Function GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states Become a Premium Member! 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Deep mutational scanning (DMS) is a powerful method for studying the functional consequences of various genetic variants within a specific gene or genomic region. This technique combines high-throughput DNA sequencing with systematic mutagenesis to create and assess the impact of many different mutations simultaneously (Araya & Fowler, 2011). It has particular relevance in the field of drug discovery, offering transformative potential across various stages of the pipeline, from target identification and validation to lead optimisation. Target Identification and Validation In drug discovery, the identification of robust drug targets is critical. DMS can be used to comprehensively assess the functional impact of mutations in a candidate protein, helping to validate whether drugs can effectively target it. By systematically mutating every amino acid in the protein and assessing the resulting phenotype, researchers can identify essential domains and residues crucial for the protein's biological function. This high-resolution mapping can confirm the protein’s role in disease pathology and highlight allosteric sites that might be more amenable to drug targeting than the active site, providing a solid rationale for prioritising it as a drug target. For example, a DMS approach has been conducted to reveal the functional importance of each residue in proton recognition in GPR68. The result suggested that, in contrast to other proton-sensitive channels and receptors, GPR68 did not have a single essential site for proton recognition. Instead, a collection of titratable residues spans from the extracellular surface to the transmembrane area, linking with canonical class A GPCR activation motifs to initiate proton-sensing GPCRs. Specifically, the study revealed that the protonation of key residues surrounding an extracellular facing cavity resulted in conformational rearrangements with TM3 as a central conduit (Howard et al., 2024).    Lead Optimisation Once potential lead compounds are identified, DMS can be employed to refine these molecules for enhanced potency, efficacy, and specificity. By examining how mutations in the target protein affect its interaction with the drug, researchers can identify which protein regions are crucial for binding the drug and which mutations affect its potency and efficacy. This data can guide the modification of the chemical structure of the lead compounds to improve potency and selectivity, thereby optimising the drug's design. Predicting and Overcoming Drug Resistance A significant challenge in drug development, particularly in the treatment of infectious diseases and cancer, is resistance. Mutations in target proteins can lead to decreased drug affinity and/or potency, rendering treatments ineffective. DMS provides a proactive approach to this problem by predicting potential resistance mutations before they are clinically observed (Pines et al., 2020). Furthermore, understanding these resistance mechanisms enables the design of next-generation drugs that either avoid these mutations or remain effective against them. It also helps in combination therapy strategies, where drugs are designed to target multiple sites or pathways simultaneously, reducing the likelihood of resistance development. Precision Medicine Finally, DMS aids in the advent of precision medicine by enabling a more detailed understanding of how genetic variation within human populations affects drug response. By evaluating a broad spectrum of mutations, DMS can help predict which patient subpopulations will respond to a drug and which might suffer adverse effects. This can guide the development of more personalised therapies tailored to the genetic makeup of individual patients, enhancing therapeutic outcomes and minimising harm. Limitations Deep mutational scanning encounters several constraints that affect its broad applicability and the interpretation of its results. The choice of model systems, such as yeast, bacteria, or mammalian cells, can heavily influence the method's effectiveness. Certain systems might not replicate the natural environment or post-translational modifications observed in humans, potentially leading to inconsistencies in how mutations influence protein function in real-world scenarios. Moreover, DMS requires considerable resources, including time, financial investment, and specialised expertise, limiting accessibility for some research laboratories. Additionally, DMS is not universally applicable to all proteins; it struggles with proteins that lack a clear function or perform multiple complex roles. Finally, current sequencing technology restricts the mutagenizable region to about 300 amino acids, although this limitation has eased from an initial 25 amino acids and is expected to further diminish as sequencing technology advances (Fowler et al., 2014). Future directions As deep mutational scanning continues to evolve, its future directions will likely focus on enhancing its scalability, accuracy, and applicability across broader biological contexts. An essential advancement will be the integration of DMS with emerging sequencing technologies that allow for longer reads and more accurate mapping of complex mutations. This could expand the method's capability to explore larger genomic regions and more intricate genetic variations. Additionally, combining DMS with computational modelling and machine learning algorithms promises to improve the predictive power of the technique, enabling more precise interpretations of how mutations affect protein function in diverse cellular environments. Another promising development is the application of DMS to a wider array of biological systems, including multicellular organisms and human cells, to better mimic physiological conditions and disease states. This would help bridge the gap between in-vitro findings and clinical outcomes. In conclusion, deep mutational scanning is a versatile tool in drug discovery, providing detailed insights that can drive the early stages of target and lead identification, combat drug resistance, and refine therapeutic indices to produce safer and more effective drugs. Reference Araya, C. L., & Fowler, D. M. (2011). Deep mutational scanning: assessing protein function on a massive scale. Trends in Biotechnology , 29 (9), 435–442. https://doi.org/10.1016/j.tibtech.2011.04.003 Fowler, D. M., Stephany, J. J., & Fields, S. (2014). Measuring the activity of protein variants on a large scale using deep mutational scanning. Nature Protocols , 9 (9), 2267–2284. https://doi.org/10.1038/nprot.2014.153 Howard, M. K., Hoppe, N., Huang, X.-P., Macdonald, C. B., Mehrotra, E., Patrick Rockefeller Grimes, Zahm, A. M., Trinidad, D. D., English, J. G., Coyote-Maestas, W., & Aashish Manglik. (2024). Molecular basis of proton-sensing by G protein-coupled receptors. BioRxiv (Cold Spring Harbor Laboratory) . https://doi.org/10.1101/2024.04.17.590000 Pines, G., Fankhauser, R. G., & Eckert, C. A. (2020). Predicting Drug Resistance Using Deep Mutational Scanning. Molecules , 25 (9), 2265. https://doi.org/10.3390/molecules25092265

Get your space suits on, GPCR cadets! The GPCR rocket is all fueled and ready to blast off into a galaxy of incredible advancements, now powered up with a series of cosmic GPCR events for the year ahead. It’s time to mark your calendars and save the dates—let’s make some stellar memories together! 🚀✨ This Week’s Highlights: Congrats to: Ya-Tzu Li , our notable contributor, for her superb undergrad paper along with Hao-Jen Hsu , Chun-Chun Chang , et al.   about State transitions of coupled Gi-protein: Insights into internal water channel dynamics within dopamine receptor D3 from in silico submolecular analyses Joseph Crecelius , Adriano Marchese , et al. for their excellent work on Receptor determinants for ß-arrestin functional specificity at C-X-C chemokine receptor 5 (CXCR5) Panjamaporn Sangwung , Alejandra Tomas , Kyle Sloop , et al. for their outstanding study on Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease Milena Malcharek , Graham Ladds , et al. for their extensive research on The role of receptor activity-modifying proteins in obesity and diabetes mellitus Maleesha Ubhayarathna , Christopher Langmead , Gregory Stewart , et al. for their fantastic review on Molecular and structural insights into the 5-HT2C receptor as a therapeutic target for substance use disorders Leigh Walker , Christopher Langmead , Andrew Lawrence , et al. for their remarkable analysis on Targeting muscarinic receptors for the treatment of alcohol use disorders: Opportunities and hurdles for clinical development 👨‍💻 Why would you want to miss out on all the fun with a DrGPCR Premium Membership ? 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Classified GPCR News  Let’s dive into the   Classified GPCR News from October 28th to November 3rd, 2024 Industry News Nxera Pharma Operational Highlights and Consolidated Results for the Third Quarter and First Nine Months of 2024 Nasdaq debutante Septerna swells its IPO to $331m Nxera Pharma and Antiverse Enter Collaboration To Design Novel GPCR- Targeted Antibody Therapeutics Using Generative AI Zombie Fungi Hijack Hosts’ Brains GPCR Therapeutics, Inc. has received Orphan Drug Designation (ODD) from the FDA for its hematopoietic stem cell mobilization agent It’s not just obesity. Drugs like Ozempic will change the world GPCR Events, Meetings, and Webinars November 5 - 7, 2024 | 16th Annual PEGS Europe   NEW November 25 - 26, 2024 | 6th International Conference on Stem Cell, Tissue Engineering and Regenerat November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe NEW December 10 - 12, 2024 | Pharmacology 2024 NEW January 13 - 16, 2025 | PepTalk 2025 NEW January 25 - 29, 2025 | SLAS 2025 NEW February 15 - 16, 2025 | Structural and Functional Approaches in GPCR Drug Discovery NEW February 15 - 19, 2025 | BPS 2025 NEW February 16 - 21, 2025 | Harnessing the Power of Advanced Multimodal Approaches to GPCR Drug Discovery NEW March 12 - 14, 2025 | NextGen Biomed 2025 NEW March 25 - 28, 2025 | 10th German Pharm-Tox Summit NEW April 1 - 5, 2025 | XXIII GEM Meeting in 2025 NEW April 3 - 6, 2025 | ASPET 2025 NEW   April 14 - 17, 2025 | 20th Drug Discovery Chemistry NEW   April 24 - 27, 2025 | American Physiology Summit 2025 NEW April 25 - 30, 2025 | AACR Annual Meeting 2025 NEW May 12 - 15, 2025 | PEGS 2025 NEW May 20 - 22, 2025 | SLAS Europe 2025 NEW June 16 - 19, 2025 | BIO International Convention 2025 July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Scientist I Cell Biology - Tectonic Therapeutic PhD fellowship in GPCR mechanosensing Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry GPCR Activation and Signaling GPCR signalling: Yet another variant route in a highly complex road map Transactivation of the EGF receptor as a novel desensitization mechanism for G protein-coupled receptors, illustrated by dopamine D2-like and β2 adrenergic receptors Receptor determinants for ß-arrestin functional specificity at C-X-C chemokine receptor 5 (CXCR5) State transitions of coupled Gi-protein: Insights into internal water channel dynamics within dopamine receptor D3 from in silico submolecular analyses GPCRs in Cardiology, Endocrinology, and Taste Adipose tissue in older individuals: a contributing factor to sarcopenia Asprosin regulates male reproduction in teleosts: an in vitro study in Channa punctata GPCRs in Neuroscience Neuron specific quantitation of Gαolf expression and signaling in murine brain tissue Regulator of G protein signaling 6 (RGS6) in dopamine neurons promotes EtOH seeking, behavioral reward, and susceptibility to relapse GPCRs in Oncology and Immunology The GPCR adaptor protein Norbin controls the trafficking of C5aR1 and CXCR4 in mouse neutrophils Mechanistic exploration of bioactive constituents in Gnetum gnemon for GPCR-related cancer treatment through network pharmacology and molecular docking The Effect of Cancer-Associated Mutations on Ligand Binding and Receptor Function - A Case for the 5-HT2C Receptor Reviews, GPCRs, and more Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors Ligand bias at the muscarinic acetylcholine receptor family: Opportunities and challenges Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease The role of receptor activity-modifying proteins in obesity and diabetes mellitus Molecular and structural insights into the 5-HT2C receptor as a therapeutic target for substance use disorders Targeting muscarinic receptors for the treatment of alcohol use disorders: Opportunities and hurdles for clinical development Chemokine CXCL13-CXCR5 signaling in neuroinflammation and pathogenesis of chronic pain and neurological diseases Structural and Molecular Insights into GPCR Function Native mass spectrometry prescreening of G protein-coupled receptor complexes for cryo-EM structure determination Molecular Basis of MC1R Activation: Mutation-Induced Alterations in Structural Dynamics Molecular determinants of neuropeptide-mediated activation mechanisms in tachykinin NK1 and NK2 receptors Become a Premium Member! 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Get ready for an expedition, GPCR explorers! Embark on another exciting exploration of the unknown realms of GPCR research. Welcome back to your weekly GPCR quest! This Week’s Highlights: Congrats to: John Teye Azietaku , our great contributor, for his article Class B1 GPCR Dimerization: Unveiling Its Role in Receptor Function and Signaling Sonja Peter , Brian Bender , Chris De Graaf   for their excellent work on Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential Today, we started the Principles of Pharmacology II   course! Thank you to all participants in Dr. Terry Kenakin's educational initiative this fall! Your dedication has greatly enriched the learning experience. Let’s keep fostering a collaborative environment for sharing ideas and expanding knowledge! We had a blast at the 11th Adhesion GPCR Workshop 2024 ! The 11th Adhesion GPCR Workshop 2024 was a successful event that brought together experts, researchers, and enthusiasts worldwide to explore Adhesion GPCRs. The presentations and discussions sparked new ideas and collaborations, shaping the future of the field. We thank all participants for their inspiring contributions and passion. Classified GPCR News  Let’s dive into the   Classified GPCR News from October 21st to 27th, 2024 Industry News UNC School of Medicine to Receive $3-Million Award from ARPA-H’s Sprint for Women’s Health Nxera Pharma Wins Biotech Company of the Year and Financing Deal of the Year at the Citeline Japan Awards 2024 GPCR therapies: Eight promising biotechs hacking the cell signaling pathway From Structure to Solution: How Structural Biology Informs the Development of Drugs Targeting G Protein-Coupled Receptors Olfactive Biosolutions Establishes Scientific Advisory Board GLP-1s like Ozempic are among the most important drug breakthroughs ever Goldman-backed drug developer Septerna raises $288 mln in US IPO Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Scientist I Cell Biology - Tectonic Therapeutic PhD fellowship in GPCR mechanosensing Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry GPCR Activation and Signaling A gain of function variant in RGS18 candidate for a familial mild bleeding syndrome Fusarium graminearum Ste2 and Ste3 Receptors Undergo Peroxidase-Induced Heterodimerization when Expressed Heterologously in Saccharomyces cerevisiae The beta 2 adrenergic receptor cross-linked interactome identifies 14-3-3 proteins as regulating the availability of signaling-competent receptors GPCRs in Neuroscience Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches Altered PLCβ/IP3/Ca2+ Signaling Pathway Activated by GPRCs in Olfactory Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia Sphingosine 1-phosphate receptor subtype 1 (S1P1) activity in the course of Alzheimer's disease GPCRs in Oncology and Immunology Characterization, expressional and evolutionary analysis of five fish-specific CCRs (CCR4La, CCR4Lc, CCR12a1, CCR12a2, and CCR12b) in largemouth bass (Micropterus salmoides) The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells Methods & Updates in GPCR Research Generation of CRISPR/Cas9 modified human iPSC line with correction of heterozygous mutation in exon 6 of the CaSR gene Reviews, GPCRs, and more Insight into structural properties of viral G protein-coupled receptors and their role in the viral infection: IUPHAR Review 41 Structural and Molecular Insights into GPCR Function Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT2A Receptors Investigating the Effect of GLU283 Protonation State on the Conformational Heterogeneity of CCR5 by Molecular Dynamics Simulations Become a Premium Member! Get your 5-day free trial TODAY!

G protein-coupled receptors (GPCRs) are membrane-bound proteins that sense external stimuli and relay signals inside the cell, resulting in various physiological outcomes. While GPCRs can exist as monomers, some types, like class C GPCRs, are obligate dimers, either as homodimers or heterodimers, with distinct conformations in both their inactive and active states [1, 2]. The possibility of dimerization in class A and class B GPCRs, however, has been more controversial, despite increasing evidence that these receptors can also form dimers. These dimeric forms, which can either be transient or stable, are believed to influence the function and regulation of GPCRs—a process known as receptor cross-talk [3]. For example, dimerization has been shown to affect signaling pathways in class A dopamine receptors like D1/D2 and D1/D3, which exhibit distinct pharmacological profiles in their dimeric form compared to their monomeric counterparts [4]. Class B1 GPCRs are an important subclass of GPCRs that include 15 receptors involved in regulating body homeostasis and metabolism, and they are activated by peptide hormones [5]. Recent studies suggest that class B1 GPCRs can form both homodimers and heterodimers, which may play a crucial role in modulating receptor function and ligand signaling. These dimeric interactions may contribute to the phenomenon of biased agonism, where ligands produce different signaling outcomes depending on the receptor conformation or dimerization state. Examples of class B1 GPCRs forming homodimers include the secretin receptor (SecR)[6] and GLP-1R [7], while GLP-1R is also known to heterodimerize with the GIPR in recombinant cell system [8]. Research using techniques like bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET) has revealed that GLP-1R homodimerization occurs via transmembrane helix 4 (TM4), which forms the interface for both homo- and heterodimers [9]. These studies also show that disrupting the dimerization of GLP-1R results in decreased high-affinity binding to its natural ligand, GLP-1, while selectively affecting receptor signaling. Such findings suggest that dimerization is critical for regulating GPCR function, particularly with respect to biased agonism, which may alter downstream signaling outcomes based on the receptor's dimeric state. One of the most intriguing examples of class B1 GPCR dimerization involves the secretin receptor (SecR). SecR dimerization enhances the receptor’s signaling efficiency by increasing its dynamics in a G protein-dependent manner [6]. This dimerization allows the N-terminal activation domain of the receptor to repeatedly engage and disengage from the receptor’s core, which is crucial for G protein recruitment. As a result, dimerized SecR receptors exhibit higher rates of G protein activation and release, improving both binding affinity and signaling potency. Additionally, the dimeric state allows rotational movement of the receptor's extracellular domain (ECD), facilitating the partial disengagement of the peptide while maintaining high-potency signaling. In summary, dimerization in class B1 GPCRs is an emerging area of research that has far-reaching implications for our understanding of GPCR function and signal transduction. While class B1 GPCRs were initially thought to function primarily as monomers, mounting evidence suggests that their ability to form dimers—whether homodimers or heterodimers—plays a critical role in regulating receptor function, ligand binding, and downstream signaling. This insight not only enhances our understanding of class B1 GPCR biology but also opens new avenues for developing therapeutic agents that target specific receptor dimer states to modulate signaling in diseases related to metabolism and homeostasis.     References   1.          Gusach, A., J. García-Nafría, and C.G. Tate, New insights into GPCR coupling and dimerisation from cryo-EM structures.  Current Opinion in Structural Biology, 2023. 80 : p. 102574. 2.          Bouvier, M., Oligomerization of G-protein-coupled transmitter receptors.  Nat Rev Neurosci, 2001. 2 (4): p. 274-86. 3.          Guo, W., et al., Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface determine activation.  Proceedings of the National Academy of Sciences, 2005. 102 (48): p. 17495-17500. 4.          Perreault, M.L., et al., Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance. Neuropsychopharmacology, 2014. 39 (1): p. 156-68. 5.          Graaf, C., et al., Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes.  Pharmacol Rev, 2016. 68 (4): p. 954-1013. 6.          Harikumar, K.G., et al., Impact of secretin receptor homo-dimerization on natural ligand binding.  Nature Communications, 2024. 15 (1): p. 4390. 7.          Harikumar, K.G., et al., Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery.  Proc Natl Acad Sci U S A, 2012. 109 (45): p. 18607-12. 8.          Schelshorn, D., et al., Lateral allosterism in the glucagon receptor family: glucagon-like peptide 1 induces G-protein-coupled receptor heteromer formation.  Mol Pharmacol, 2012. 81 (3): p. 309-18. 9.          Wootten, D., et al., Allostery and Biased Agonism at Class B G Protein-Coupled Receptors.  Chem Rev, 2017. 117 (1): p. 111-138.

Hello GPCR Passenger, Welcome aboard the GPCR train as it sets off on its journey. We are excited to have you back at your usual GPCR stop for the week. Let's explore the newest developments in GPCR research and community news together! This Week’s Highlights: Congrats to: Monserrat Avila-Zozaya , our incredible contributor, for her fantastic article on Profiling Immune Cell and Platelet Transcriptomes , and we want to wish her the best of luck on her talk today at the 11th Adhesion GPCR Workshop about ' Breaking Barriers: My Journey from Mexico to the Heart of the Dr. GPCR Ecosystem and beyond .' We all are cheering for you! Gunnar Schulte for his excellent work on International Union of Basic and Clinical Pharmacology CXV: The Class F of G Protein-Coupled Receptors Avoid delaying it further! Registrations end TOMORROW for Principles of Pharmacology II Don't let this opportunity slip away to reserve your spot in our upcoming course ! Seize the chance to enhance your understanding and expertise in pharmacology under the guidance of the renowned expert Dr. Terry Kenakin . Participants will acquire knowledge in: The powerful applications of new cellular assays to determine GPCR ligand behavior in different functional systems. Understanding real-time kinetics to predict activity and in vivo target coverage. New ligands and new GPCR behaviors that produce unique drug profiles (i.e. intracellular ligands and signaling, location bias, signaling bias). Modules: October 31st: The Eyes to See- The Importance of Pharmacologic Assays. November 7th: Drug Disposition in Physiological Tissues as a Therapeutic Variable. November 14th: The Application of GPCR Ligand Kinetics to Candidate Design. November 21st: Unconventional GPCR Ligands as Drugs. December 5th: Unique Exploitable GPCR-Ligand Behaviors for Therapeutic Benefit. *Lessons are every Thursday at 10 AM EST. Reasons to Consider Enrolling Now: Exciting Q&A Session and Group Discussions Don't miss out on the opportunity to get your questions answered by our knowledgeable teacher or initiate a lively discussion in the exclusive group dedicated to the course! Outstanding Educational Opportunities at an Unbeatable Value Our courses provide top-notch education at a competitive price. Tailored Learning Experience Designed for Your Needs Enhance your learning journey with access to our extensive library of recorded sessions. High Praise from Our Happy Students Past students highly endorse our programs, praising our faculty's engaging content and expertise in simplifying complex GPCR pharmacology concepts for practical use in academic and industrial settings. Exclusive Deal for Scientists in Developing Nations If you reside and work in a developing country, complete this form for free access to Dr. Kenakin's upcoming course. We aim to make education accessible to all! Act now to become a part of our prestigious learning community! Classified GPCR News  Let’s dive into the   Classified GPCR News from October 14th to 20th, 2024 Industry News Ghent based Confo Therapeutics is leveraging GPCR expertise as a discovery engine - multiple partners have already signed on to the science Lundbeck signs $2.5B check for Longboard, seeing blockbuster potential in epilepsy med Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Scientist I Cell Biology - Tectonic Therapeutic Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   GPCR Activation and Signaling Opioid receptors reveal a discrete cellular mechanism of endosomal G protein activation Amylin receptor subunit interactions are modulated by agonists and determine signaling Distinct role of GRK3 in platelet activation by desensitization of G protein-coupled receptors GPCRs in Cardiology, Endocrinology, and Taste Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments GPCRs in Neuroscience An emerging multi-omic understanding of the genetics of opioid addiction A FMRFamide-like neuropeptide FLP-12 signaling regulates head locomotive behaviors in C. elegans GPCRs in Oncology and Immunology In Silico Design of Novel RGS2-Galpha-q Interaction Inhibitors with Anticancer Activity Evolutionary diversity of CXCL16-CXCR6: Convergent substitutions and recurrent gene loss in sauropsids Noval insights and therapeutic strategies for tumor-induced kidney pathologies Methods & Updates in GPCR Research Development of a NanoBRET Assay Platform to Detect Intracellular Ligands for the Chemokine Receptors CCR6 and CXCR1 Reviews, GPCRs, and more International Union of Basic and Clinical Pharmacology CXV: The Class F of G Protein-Coupled Receptors Structural and Molecular Insights into GPCR Function Structure of endothelin ETB receptor-Gi complex in a conformation stabilized by unique NPxxL motif Ligand-induced conformational changes in the β1-adrenergic receptor revealed by hydrogen-deuterium exchange mass spectrometry Become a Premium Member! 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G protein-coupled receptors (GPCRs) are integral to cellular signaling, influencing a wide array of physiological processes and serving as critical targets for therapeutic interventions. Recent advancements in transcriptomic profiling have provided new insights into the expression patterns of GPCRs across different cell types. A study published in Scientific Data by Arne Hansen et a l has introduced a sensitive method for detecting GPCR mRNAs in human immune cells and platelets, revealing significant findings that enhance our understanding of GPCRs' roles in immune function and potential therapeutic applications. The study reports that human white blood cells express an average of 160 GPCR mRNAs, ranging from 123 to 206, while platelets exhibit a distinct profile with 69 GPCR mRNAs. This analysis utilized a semi-quantitative multiplex PCR method, which allowed for the detection of both abundant and rare GPCR transcripts. The researchers found that certain GPCRs, such as vasopressin receptors, were expressed in hematopoietic stem cells, suggesting a potential role in regulating red blood cell production and offering a novel avenue for treating anemia. Additionally, the study identified unique expression patterns of GPCRs in different immune cell types, including B cells, CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and dendritic cells. For instance, the expression of specific chemokine receptors in monocytes and macrophages indicates their involvement in immune cell trafficking and inflammatory responses. The researchers conducted a comparative analysis with previous studies, notably the work by Groot-Kormelink et al., which reported 165 GPCR mRNAs in alveolar macrophages. The current study found that 133 of these receptors were also detected, highlighting the robustness of the assay and the potential for cross-validation of GPCR expression across different cell types. However, the study also noted discrepancies, with 26 receptors identified in the previous study not detected in the current analysis, suggesting that variations in cell preparation and assay sensitivity could influence results. The identification of a diverse array of GPCRs in immune cells underscores their potential roles in modulating immune responses and highlights the need for further functional studies to elucidate their specific contributions.Moreover, the study's findings on the unique expression of chemokine receptors in monocytes and macrophages suggest that these GPCRs could be targeted to modulate inflammatory responses, offering potential therapeutic avenues for conditions such as autoimmune diseases and chronic inflammation. The ability to profile GPCR expression in a highly sensitive manner also opens doors for exploring the roles of these receptors in various pathological states, including cancer and infectious diseases. Therefore this study significantly advances our understanding of GPCR expression in human immune cells and platelets, providing a valuable resource for future research. As the field continues to evolve, the insights gained from this research will be instrumental in shaping therapeutic strategies for a range of immune-related conditions. For further details, refer to the full article: DOI: 10.1038/s41597-024-03880-2

Hey there, GPCR Enthusiasts! Ready for your GPCR quest, so bold and bright? Join us now, and let's explore with all our might! 🎇 This Week’s Highlights: Congrats to: Remi Janicot , and Mikel Garcia-Marcos for their excellent work on Protocol to investigate G protein-coupled receptor signaling kinetics and concentration-dependent responses using ONE-GO biosensors Why wait any longer to sign up for Principles of Pharmacology II ? Act fast to secure your place in our upcoming course ! Don't miss out on this chance to elevate your knowledge and skills in pharmacology! Registration closes NEXT WEEK!! What are the main objectives of the course? Allow registrants to appreciate the incredible versatility of GPCRs and how small molecules can affect their behavior for therapeutic benefit. What will students gain from taking this course? Learn how to therapeutically exploit GPCRs (Physiology’s ‘Swiss Army Knife’) vast repertoire of ways to control cell function. Apply unique pharmacologic assays and unconventional ligands to unveil GPCR activities. Adjust ligand kinetics and tissue disposition for optimal therapeutic activity. *Lessons are every Thursday at 10 AM EST. 📌 Reasons to Consider Enrolling Now: Exceptional Educational Opportunities at Unbeatable Value Our courses are designed to provide top-notch quality at an affordable price point. Dynamic Learning Environment Tailored to Your Needs Maximize your learning experience by accessing our comprehensive library of recorded sessions. Rave Reviews from Our Satisfied Students Past students highly recommend our programs, praising our faculty's engaging content and expertise in simplifying complex GPCR pharmacology concepts for practical use in academia and industry. Exclusive Deal for Scientists in Developing Nations If you reside and work in a developing country, complete this form for free access to Dr. Kenakin's upcoming course. We aim to make education accessible to all! Take action immediately to join our esteemed learning community! GPCR Event Spotlight 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23 - 25, 2024 Get ready to party with GPCRs next week! 🎉 We are bouncing off the walls with excitement to meet you all and geek out about GPCRs. If you haven't signed up, hurry up before the GPCR train leaves the station! Get ready to be blown away by our fantastic lineup of speakers HERE ! Want to elevate your brand to the next level? Contact Hello@DrGPCR.com for sponsorship opportunities .  Let's make your brand shine like never before! Classified GPCR News  Let’s dive into the   Classified GPCR News from October 7th to 13th, 2024 Industry News Antiverse Raises £3.5M ($4.6M) to Advance Generative AI Antibody Design Platform GPCR Safety Panels Launched Crinetics Pharmaceuticals Announces October 2024 Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Neurocrine Biosciences Announces Conference Call and Webcast of Third Quarter 2024 Financial Results Novel full MC4 receptor-specific nanobody described Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position GPCR Activation and Signaling Diverse pathways in GPCR-mediated activation of Ca2+ mobilization in HEK293 cells Activation of polycystin-1 signaling by binding of stalk-derived peptide agonists A role for plasma membrane Ca2+ ATPases in regulation of cellular Ca2+ homeostasis by sphingosine kinase-1 GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signaling pathway GPCR Binders, Drugs, and more Global analysis of neuropeptide receptor conservation across phylum Nematoda Target-based discovery of antagonists of the tick (Rhipicephalus microplus) kinin receptor identifies small molecules that inhibit midgut contractions GPCRs in Cardiology, Endocrinology, and Taste Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract Intracellular TAS2Rs act as a gatekeeper for the excretion of harmful substances via ABCB1 in keratinocytes GPCRs in Neuroscience Ventral tegmental area amylin / calcitonin receptor signaling suppresses feeding and weight gain in female rats Neuropeptide and serotonin co-transmission sets the activity pattern in the C. elegans egg-laying circuit Methods & Updates in GPCR Research High-throughput G protein-coupled receptor-based autocrine screening for secondary metabolite production in yeast Protocol to investigate G protein-coupled receptor signaling kinetics and concentration-dependent responses using ONE-GO biosensors Structural and Molecular Insights into GPCR Function Structural insights into KSHV-GPCR constitutive activation and CXCL1 chemokine recognition Structural basis of psychedelic LSD recognition at dopamine D1 receptor Structural basis of μ-opioid receptor targeting by a nanobody antagonist Probing the energy landscape of the lipid interactions of the serotonin1A receptor Potential allosteric pockets identification of glucagon receptor based on molecular dynamics simulations Leukotriene B4 receptor 1 (BLT1) activation by leukotriene B4 (LTB4) and E resolvins (RvE1 and RvE2) Become a Premium Member! 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Hey there, GPCR Enthusiasts! Are you geared up for your GPCR fix of the day? Get ready to dive into some discoveries and mind-blowing breakthroughs with us! This Week’s Highlights: Congrats to: Our contributor, Cam Sinh Lu ,  who has just released an incredible article on our site and a GPCR Paper with his team: Targeted Drug Design through GPCR Mutagenesis: Insights from β2AR China M Payne ,   Cam Sinh Lu ,   Karen Gregory ,  Lauren May ,  Andrea Vernall , et al. for their fantastic paper on Development of Putative Bivalent Dicovalent Ligands for the Adenosine A1 Receptor Bryan Roth  and Brian Krumm  for their excellent study on Molecular glues as potential GPCR therapeutics Sabrina Rahman , Arthur Christopoulos , Christopher Langmead , et al. for their outstanding work on Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated pathways Get ready for the Second class of Principles of Pharmacology I We are diving into the second class of our Principles of Pharmacology I course with enthusiasm and determination! If you missed out on enrolling in this one, worry not – a spot is reserved just for you in Principles of Pharmacology II . Secure your spot now for our next course . Seize this opportunity to enhance your expertise and proficiency in pharmacology! We close registrations in 2 weeks!! Registrants will learn: The powerful applications of new cellular assays to determine GPCR ligand behavior in different functional systems. Understanding real-time kinetics to predict activity and in vivo target coverage. New ligands and new GPCR behaviors that produce unique drug profiles (i.e. intracellular ligands and signaling, location bias, signaling bias). Modules: October 31st : The Eyes to See- The Importance of Pharmacologic Assays. November 7th : Drug Disposition in Physiological Tissues as a Therapeutic Variable. November 14th : The Application of GPCR Ligand Kinetics to Candidate Design. November 21st : Unconventional GPCR Ligands as Drugs. December 5th : Unique Exploitable GPCR-Ligand Behaviors for Therapeutic Benefit. *Lessons are every Thursday at 10 AM EST. 📌 Reasons to Consider Enrolling Now: Cost-effective and Unique Educational Opportunities Our courses offer affordability without compromising on quality. Adaptable Learning Environment Benefit from the flexibility of accessing recorded sessions to deepen your comprehension. Positive Feedback from Our Esteemed Students Past students highly recommend our programs, lauding the course content and the exceptional faculty members who adeptly simplify the intricacies of GPCR pharmacology for practical application in both academic and industrial research settings. Exclusive Deal for Scientists in Developing Nations If you reside and work in a developing country, complete this form for free access to Dr. Kenakin's upcoming course. We aim to make education accessible to all! Take action immediately to join our esteemed learning community! GPCR Event Spotlight 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23 - 25, 2024 Hurry, there are only a couple of weeks left! Act now to secure your spot, prepare to spark your passion, and interact with your exceptional peers to explore the latest advancements in adhesion GPCR biology! 🌟 Get ready - the full agenda is now available; check it HERE ! Are you ready to significantly boost your brand? Contact Hello@DrGPCR.com for exciting sponsorship opportunities .  Let's elevate your brand together! Classified GPCR News  Let’s dive into the   Classified GPCR News from September 30th to October 6th, 2024 Industry News Nxera Pharma appoints experienced commercial R&D executive Makoto Sugita as Chief Medical Officer and President of Nxera Pharma Japan Septerna files for IPO on strength of preclinical data, vision for expanding GPCR landscape The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2024 Septerna Announces Initiation of Phase 1 Clinical Trial with SEP-786, a Novel Oral Small Molecule PTH1R Agonist for the Treatment of Hypoparathyroidism World first: Australian scientists uncover “plant-like” behavior in important human cell regulator, opening up a new drug target for cancer, other diseases Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan HIGHLIGHT Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position GPCR Activation and Signaling Preassembly of specific Gβγ subunits at GABAB receptors through auxiliary KCTD proteins accelerates channel gating Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated pathways Postsynaptic Density Proteins and Their Role in the Trafficking of Group I Metabotropic Glutamate Receptors Dual regulation of IP3 receptors by IP3 and PIP2 controls the transition from local to global Ca2+ signals Coordinated cellular behavior regulated by epinephrine neurotransmitters in the nerveless placozoa Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3 SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor GPCR Binders, Drugs, and more Molecular glues as potential GPCR therapeutics N-acyl glycines produced by commensal bacteria potentiate GLP-1 secretion as GPCR ligands Development of Putative Bivalent Dicovalent Ligands for the Adenosine A1 Receptor GPCRs in Cardiology, Endocrinology, and Taste Ciliary localization of GPR75 promotes fat accumulation in mice GPCRs in Neuroscience Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease Identification of immune-related hub genes in spinal cord injury GPCRs in Oncology and Immunology Biochemical pharmacology of adenylyl cyclases in cancer Olfactory Receptors and Tumorigenesis: Implications for Diagnosis and Targeted Therapy Methods & Updates in GPCR Research Protocol for detecting endogenous GPCR activity in primary cell cultures using ONE-GO biosensors Quantitation of F-actin in cytoskeletal reorganization: Context, methodology and implications Structural and Molecular Insights into GPCR Function LYCHOS is a human hybrid of a plant-like PIN transporter and a GPC R Biochemical characterization of Prokineticin 2 binding to Prokineticin receptor 1 in zebrafish Coupling and Activation of the β1 Adrenergic Receptor - The Role of the Third Intracellular Loop Become a Premium Member! 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After discussing the fundamentals and applications of mutagenesis in GPCR studies (Lu, 2024), a case study is essential to deepen understanding and apply this approach in a practical context. To achieve this, the work of Heydenreich et al. (2023) will be analysed to demonstrate how mutagenesis can be employed in GPCR research and drug discovery. This paper thoroughly investigated the role of single amino acid changes to clarify the molecular mechanisms governing ligand efficacy and potency at the β2 adrenergic receptor (β2AR). The study focused on two critical pharmacological properties: efficacy and potency. Through an in-depth mutational analysis of β2AR, the researchers identified specific residues that influence these properties. This case study underscores the critical importance of mutagenesis in GPCR research. Rational Drug Design One immediate application of this research lies in rational drug design . By identifying key β2AR residues that influence efficacy and potency, pharmaceutical researchers can create drugs that precisely modulate receptor responses. The study distinguishes between driver residues , which directly influence signal transduction, and modulator residues , which affect nearby regions but do not make active state-specific contacts. This distinction is essential for designing drugs that selectively target these residues to achieve desired pharmacological effects. For example, orthosteric drug design —in which drugs bind to the receptor’s primary active site—can now be optimised by targeting specific ligand-receptor interactions to modify efficacy and potency. Alternatively, allosteric modulators , which bind to sites outside the traditional ligand-binding pocket, can be designed to regulate receptor function indirectly. Allosteric modulators offer a promising approach for developing drugs that enhance or inhibit receptor activity without directly competing with ligands, potentially reducing side effects and increasing therapeutic specificity. Interestingly, only 10 out of 82 important residues are within the ligand-binding pocket, resulting in a significant opportunity for developing allosteric modulators.  Personalised Medicine Another significant application of these findings is in personalised   medicine . The identification of pharmacologically significant residues enables more accurate predictions of how genetic variations, such as single nucleotide polymorphisms (SNPs), might impact receptor function. GPCRs, including β2AR, play key roles in various conditions, such as asthma, cardiovascular diseases, and metabolic disorders. By understanding how different SNPs affect β2AR function, it becomes possible to tailor therapies based on an individual's genetic profile. For instance, a patient with a specific variant of the β2AR gene that reduces potency might require a higher drug dose to achieve the same effect as someone with the wild-type gene. This personalised approach could optimise drug efficacy while minimising adverse effects, improving treatment outcomes for conditions influenced by β2AR signalling. Evolutionary Insights and Drug Design From an evolutionary standpoint, the study reveals that residues critical for β2AR function are under intense selective pressure, while others are more mutation-tolerant. This suggests that conserved residues across species may be ideal drug targets, ensuring consistent efficacy across diverse patient populations or species. Understanding the evolutionary conservation of these residues can lead to the development of drugs that are less likely to lose effectiveness due to genetic variation. Conclusion In summary, the findings of this study have significant implications for drug design, personalised medicine, and therapeutic interventions. By pinpointing the molecular determinants of ligand efficacy and potency in GPCR signalling, this research provides a foundation for the development of more targeted and effective drug therapies. These insights have the potential to advance the treatment of various diseases involving GPCR signalling, leading to improved patient outcomes and fewer side effects. While this case study highlights the essential role of mutagenesis in GPCR research, it is not the only example. Deep mutational scanning, for instance, is gaining popularity as a strategy due to its ability to comprehensively screen every residue within the receptors (Howard et al., 2024). In the next article, we will explore this emerging field in greater detail. Reference Cam Sinh Lu. (2024, September 3). Decoding GPCR Function: The Role of Mutagenesis in Rational Drug Discovery. Dr. GPCR Ecosystem; Dr. GPCR Ecosystem. https://www.ecosystem.drgpcr.com/post/decoding-gpcr-function-the-role-of-mutagenesis-in-rational-drug-discovery Heydenreich, F. M., Marti-Solano, M., Sandhu, M., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023). Molecular determinants of ligand efficacy and potency in GPCR signaling. Science , 382 (6677), eadh1859. Howard, M. K., Hoppe, N., Huang, X. P., Macdonald, C. B., Mehrota, E., Grimes, P. R., ... & Manglik, A. (2024). Molecular basis of proton-sensing by G protein-coupled receptors. bioRxiv .

Welcome aboard, GPCR Crew! Let's set sail towards exciting discoveries and groundbreaking achievements together! This Week’s Highlights: Our fearless leader, Yamina Berchiche , is gearing up to rock the mic today at the 22nd Discovery on Target ! We're sending you all the good vibes and a sprinkle of birthday magic for an epic celebration! 🚀🎉 Kilian Roßmann , Joshua Levitz , Johannes Broichhagen for their excellent work on Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology First day of class! Thrilling beginning to Principles of Pharmacology I We are excited to announce the start of our Principles of Pharmacology I course! If you snoozed on signing up for this one, fret not – there's always a spot waiting for you in Principles of Pharmacology II . Registration is open for our November class . Don’t miss this opportunity to advance your knowledge and skills in pharmacology! Registrants will learn: The powerful applications of new cellular assays to determine GPCR ligand behavior in different functional systems. Understanding real-time kinetics to predict activity and in vivo target coverage. New ligands and new GPCR behaviors that produce unique drug profiles (i.e. intracellular ligands and signaling, location bias, signaling bias). Modules: October 31st : The Eyes to See- The Importance of Pharmacologic Assays. November 7th : Drug Disposition in Physiological Tissues as a Therapeutic Variable. November 14th : The Application of GPCR Ligand Kinetics to Candidate Design. November 21st : Unconventional GPCR Ligands as Drugs. December 5th : Unique Exploitable GPCR-Ligand Behaviors for Therapeutic Benefit. *Lessons are every Thursday at 10 AM EST. 🔥 Why You Should Enroll Now: Budget-Friendly & Distinctive Educational Experience Affordable courses that maintain high-quality standards. Flexible Learning Access recorded sessions at your convenience to enhance your understanding. Our Students Highly Recommend Us! Past students praise the course content and our exceptional professors' ability to simplify the complexity of GPCR pharmacology and apply it to their research in academia and industry. Exclusive Deal for Scientists Residing and Working in Developing Nations If you live and work  in a developing country, please complete this form to enjoy complimentary access to Dr. Kenakin's upcoming course. Our goal is to ensure that education is within reach for everyone! Act Now and Become a Valued Member of our Learning Community! GPCR Event Spotlight 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23 - 25, 2024 Get ready to ignite your passion and connect with your amazing peers to dive into the cutting-edge advancements in adhesion GPCR biology! 🌟 Get pumped up - the complete agenda is live; don't miss out HERE ! Ready to elevate your brand to new heights? Get in touch with Hello@DrGPCR.com for exciting sponsorship opportunities ! Let's take your brand to the next level together! Classified GPCR News  Let’s dive into the   Classified GPCR News from September 23rd to 29th, 2024 Industry News Superluminal Medicines Announces Formation of Scientific Advisory Board Generate:Biomedicines Announces Multi-Target Collaboration with Novartis to Discover and Develop Protein Therapeutics with Generative AI Nxera Pharma receives approval of insomnia drug in Japan Lilly and Novo Spend Billions to Expand Obesity Pipelines Beyond GLP-1s Septerna Announces Initiation of Phase 1 Clinical Trial with SEP-786, a Novel Oral Small Molecule PTH1R Agonist for the Treatment of Hypoparathyroidism Confo Therapeutics Announces Publication in Nature Communications Demonstrating First-Ever Structure of a Complex Between an Antibody-based Agonist and a Class A GPCR Regulating Hunger and Satiety OMass Therapeutics Expands Development Team with Key Appointments in US and UK and Announces the Nomination of Clinical Candidate Against MC2 Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan HIGHLIGHT Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Adhesion GPCRs The G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration GPCR Activation and Signaling Subcellular activation of β-adrenergic receptors using a spatially restricted antagonist GPCR Binders, Drugs, and more Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology GPCRs in Cardiology, Endocrinology, and Taste Rap1A Modulates Store-Operated Calcium Entry in the Lung Endothelium: A Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability GPCRs in Neuroscience Virtual screening, molecular docking and dynamics simulation studies to identify potential agonists of orphan receptor GPR78 targeting CNS disorders Predicting biological activity and design of 5-HT6 antagonists through assessment of ANN-QSAR models in the context of Alzheimer's disease GPCRs in Oncology and Immunology Aberrant hormone receptors regulate a wide spectrum of endocrine tumors G protein coupled receptor transcripts in human immune cells and platelets Methods & Updates in GPCR Research Simultaneous spectral illumination of microplates for high-throughput optogenetics and photobiology A deep learning framework combining molecular image and protein structural representations identifies candidate drugs for pain Reviews, GPCRs, and more The role of G protein-coupled receptors and their ligands in animal domestication The repertoire of G-protein-coupled receptor variations in the Japanese population 54KJPN Structural and Molecular Insights into GPCR Function Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing Reliability of AlphaFold2 Models in Virtual Drug Screening: A Focus on Selected Class A GPCRs Become a Premium Member! 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Ahoy, GPCR Crew! Instead of just staying up to date, dive in, broaden your knowledge, and pave the way in the fantastic world of the GPCR field! This Week’s Highlights: Celebrating Excellence: Hyoungjun Ham , Yamina Berchiche , Thomas Sakmar , Vladimir Katanaev , Helen Su , et al. for their fantastic work on Germline mutations in a G protein identify signaling cross-talk in T cells Victoria Saca , Colin Burdette , and Thomas Sakmar for their excellent study on GPCR Biosensors to Study Conformational Dynamics and Signaling in Drug Discovery 🚨 LAST CHANCE! DEADLINES IS TOMORROW!   Early Bird Discount Ends Tomorrow! 🕒 Get 25% OFF and save big! Become a Premium Member to access both courses at a reduced price. This is your chance to get the whole experience of our comprehensive pharmacology courses for less! Are you not a premium member yet?  No worries – you can sign up for a 5-day FREE trial! Gain access to over 500 minutes of recorded classes in our  GPCR courses   taught by Drs. Terry Kenakin  and Sam Hoare ! Registration Closes Tomorrow! 🕒 Secure your spot now, and don't miss out on this essential course. Time is running out! Topics: Pharmacologic activity measurement, mechanisms of action, and GPCR discovery strategies. Mark your calendars and make sure to enroll before the deadline! *Lessons are every Thursday at 10 AM EST. 🔥 Why You Should Enroll Now: Budget-Friendly & Distinctive Educational Experience Affordable courses that maintain high-quality standards. Flexible Learning Access recorded sessions at your convenience to enhance your understanding. Our Students Highly Recommend Us! Past students praise the course content and our exceptional service. Join us for a stimulating conversation with Dr. Terry Kenakin to acquire valuable insights and prepare for the upcoming courses. Do not overlook this beneficial opportunity! Exclusive Deal for Scientists Residing and Working in Developing Nations If you live and work  in a developing country, please complete this form to enjoy complimentary access to Dr. Kenakin's upcoming courses. Our goal is to ensure that education is within reach for everyone! Take Action Now and Join our Community of Learners! GPCR Event Spotlight Discovery on Target’s 19th Annual GPCR-Based Drug Discovery Targeting G Protein-Coupled Receptors for New Therapeutic Options 📍  Boston, MA 📅 October 2 -3, 2024 Come and join top scientists in exploring the latest breakthroughs in GPCR-targeted drug development! Dive into the exciting world of incorporating machine learning, innovative biophysical methods, and medicinal chemistry to push the boundaries of scientific discovery! Register now for the GPCR Drug Discovery Conference and unlock incredible savings of $200 using the exclusive discount code DRGPCR24 ! Don't miss out on this fantastic opportunity! 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23 - 25, 2024 Get ready to connect with your peers and explore the cutting-edge advancements in adhesion GPCR biology! 🌟 Exciting news - the complete agenda is live; check it out HERE ! Let's dive in and make the most of this incredible opportunity! Are you looking to elevate your brand to new heights? Reach out to Hello@DrGPCR.com for exciting sponsorship opportunities ! Let's take your brand to the next level together! Classified GPCR News  Let’s dive into the   Classified GPCR News from September 16th to 22nd, 2024 Industry News Inversago Pharma’s INV-347 improves metabolic dysfunction in obese mice Aneesh Karatt Vellatt (CSO & Co-Founder, Maxion Therapeutics) – BioLeader Interview Tectonic Therapeutic Announces Favorable Phase 1a Safety, Tolerability and PK/PD Results for Lead Program TX45 Adenosine A2a receptor: novel biophysical fragment screening using polymer-encapsulated nanodiscs Google DeepMind And Isomorphic Labs Are Making Rapid Progress In Biology And Drug Discovery GLP-1/FGF21 dual agonist ZT-003 shows promising results for metabolic disorders INDIGO Biosciences, INC as a Preferred Supplier at Prendio Crinetics Pharmaceuticals announces executive departure Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan HIGHLIGHT Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position GPCR Activation and Signaling Germline mutations in a G protein identify signaling cross-talk in T cells Comparative analysis of formyl peptide receptor 1 and formyl peptide receptor 2 reveals shared and preserved signalling profiles GPCRs in Cardiology, Endocrinology, and Taste Cyclic adenosine monophosphate critically modulates cardiac GLP-1 receptor's anti-inflammatory effects GPCRs in Neuroscience Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1P1 receptor-mediated G-protein activation in a mouse model of sciatic nerve injury GPCRs in Oncology and Immunology GPR37 promotes colorectal cancer against ferroptosis by reprogramming lipid metabolism via p38-SCD1 axis Methods & Updates in GPCR Research GPCRSPACE: A New GPCR Real Expanded Library Based on Large Language Models Architecture and Positive Sample Machine Learning Strategies Reviews, GPCRs, and more GPCR Biosensors to Study Conformational Dynamics and Signaling in Drug Discovery Flavors of GPCR signaling bias Glucagon-like peptide-1 receptor: mechanisms and advances in therapy Become a Premium Member! 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Biased agonism is a phenomenon where different ligands acting on the same receptor trigger distinct signaling pathways, leading to varied biological outcomes [1]. This concept is gaining significant attention in drug discovery, especially in the context of G protein-coupled receptors (GPCRs) like the glucagon-like peptide-1 receptor (GLP-1R). The GLP-1R, a class B1 GPCR, is integral to metabolic regulation, particularly in glucose homeostasis and insulin secretion, making it a well-established target for treating type 2 diabetes and obesity [2]. It is primarily coupled to the Gs protein, which leads to the production of cyclic AMP (cAMP). However, GLP-1R can also engage other G proteins, such as Gi/o and Gq/11, leading to different downstream effects, such as inhibition of cAMP production or mobilization of intracellular calcium, respectively [3]. Additionally, GLP-1R couple to G protein-coupled receptor kinases (GRKs) and recruit β-arrestins, adding another layer of complexity to its signaling [4]. Biased agonism at the GLP-1R has been extensively studied, revealing that different ligands can stabilize distinct receptor conformations, leading to diverse signaling outcomes. Compared to the endogenous ligand GLP-1, another endogenous ligand, oxyntomodulin, exhibits a bias towards extracellular signal-regulated kinase (ERK) phosphorylation [5]. In contrast, exendin-P5, another GLP-1R agonist, is biased towards cAMP accumulation but with reduced β-arrestin recruitment, relative to GLP-1 [6]. These differences in signaling profiles can have significant physiological implications. For example, in vivo studies in diabetic models have shown that although exendin-P5 induces lower insulin release compared to exendin, both ligands exhibit similar efficacy in lowering blood glucose levels. Moreover, exendin-P5 has been observed to reduce adipose tissue size more effectively than exendin, suggesting that biased agonism can lead to distinct therapeutic outcomes. The molecular mechanisms underlying biased agonism at the GLP-1R are beginning to be elucidated through a combination of mutagenesis, pharmacological studies, and structural analysis. Research by Prof. Denise Wootten and colleagues has highlighted the importance of extracellular loop 2 (ECL2) in stabilizing the receptor conformation necessary for Gs protein recruitment and cAMP production [5]. In contrast, ligands like oxyntomodulin that preferentially activate ERK1/2 signaling interact more significantly with extracellular loop 3 (ECL3). Cryo-electron microscopy (cryo-EM) structures of GLP-1R bound to different agonists have provided further insights into how specific regions of the receptor contribute to biased signaling. For instance, the interaction of GLP-1 with ECL3, which leads to a tight conformation of the receptor's transmembrane domain (TM), contrasts with the looser interaction seen with biased agonists like exendin-P5, peptide-19, CHU-138 and TT-OAD2 [7]. These agonists exhibit less interaction with ECL3, resulting in an open conformation of the TM6-ECL3-TM7 axis, which is associated with their bias towards cAMP production and reduced β-arrestin recruitment. The concept of biased agonism has been effectively leveraged in drug discovery, as demonstrated by the development of tirzepatide, a GLP-1R/GIPR dual agonist. Tirzepatide's success underscores the potential of designing drugs that selectively target beneficial signaling pathways. Tirzepatide’s superior effect over semaglutide has been attributed in part to biased agonism at the GLP-1R. Tirzepatide is a full agonist for cAMP production at the GLP-1R which minimal ability to recruit β-arrestins, relative to GLP-1 [8-10].   In conclusion, biased agonism at the GLP-1R represents a promising strategy for optimizing therapeutic outcomes in metabolic diseases. By selectively targeting specific signaling pathways, it is possible to develop drugs with improved efficacy, as exemplified by tirzepatide. As our understanding of the molecular basis of biased agonism continues to grow, it is likely to play an increasingly important role in the design of next-generation therapeutics. Indeed, incretin-based drugs like Novo Nordisk's Wegovy and Eli Lilly's Zepbound are advancing diabetes and obesity management, driving the obesity market toward $66 billion by 2030 and on track to become one of the most lucrative drug classes, potentially reaching $100-200 billion in annual sales [11]. References 1.          Kenakin, T. and A. Christopoulos, Signalling bias in new drug discovery: detection, quantification and therapeutic impact.  Nat Rev Drug Discov, 2013. 12 (3): p. 205-16. 2.          Drucker, D.J., Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.  Cell Metab, 2018. 27 (4): p. 740-756. 3.          AZIETAKU, J.T., Profiling Glucagon-Like Peptide -1 Receptor Transducer Coupling, Signalling and Biased Agonism . 2023, Monash University. 4.          McNeill, S.M., et al., The role of G protein-coupled receptor kinases in GLP-1R β-arrestin recruitment and internalisation.  Biochemical Pharmacology, 2024. 222 : p. 116119. 5.          Wootten, D., et al., The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.  Cell, 2016. 165 (7): p. 1632-1643. 6.          Zhang, H., et al., Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects.  Nat Commun, 2015. 6 : p. 8918. 7.          Cary, B.P., et al., New Insights into the Structure and Function of Class B1 GPCRs.  Endocr Rev, 2023. 44 (3): p. 492-517. 8.          Willard, F.S., et al., Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.  JCI Insight, 2020. 5 (17). 9.          Anson, M., et al., Incidence of new onset type 2 diabetes in adults living with obesity treated with tirzepatide or semaglutide: real world evidence from an international retrospective cohort study. eClinicalMedicine, 2024. 75 . 10.        Rodriguez, P.J., et al., Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.  JAMA Internal Medicine, 2024. 184 (9): p. 1056-1064. 11. https://www.evaluate.com/thought-leadership/obesity-the-next-questions/

Greetings, Pioneers of GPCR Science! Embark on this week’s thrilling updates in GPCR research, learning opportunities, and industry developments. Don’t just stay informed—immerse yourself, expand your knowledge, and become a trailblazer in the field! This Week’s Highlights: Celebrating Excellence: Wessel A. C. Burger , Arthur Christopoulos , David M. Thal , et al., for their groundbreaking work on Positive allosteric modulation of a GPCR ternary complex Unlock Your Learning: Limited Spots Available! There are only 5 spots left for our upcoming courses, so seize the chance to learn from the best in the field. 🚨 Hurry to reserve your spot for the Principles of Pharmacology I & II BUNDLE before the Early Bird Deadline on September 27 . With just one week left, becoming a premium member is all it takes to benefit from this discount! Not a premium member yet?  No worries – you can sign up for a 5-day FREE trial! Gain access to over 500 minutes of recorded classes in our  GPCR courses   taught by Drs. Terry Kenakin  and Sam Hoare ! Every Thursday at 10 AM EST: Principles of Pharmacology I Dates: October 3, 10, 17, 24 (four sessions) Topics: Pharmacologic activity measurement, mechanisms of action, and GPCR discovery strategies. Registration deadline: September 27, 2024 Principles of Pharmacology II Dates: October 31, November 7, 14, 21, December 5 (five sessions) (we skipped Thanksgiving, of course!) Topics: New cellular assays, real-time kinetics, and unique GPCR behaviors. Registration deadline: October 25, 2024 🔥 Why You Should Enroll Now: Cost-effective & Distinctive Educational Experience Affordable courses that maintain high-quality standards. Adaptable Learning Access recorded sessions at your convenience to enhance your understanding. Our Students Highly Recommend Us! Previous students praise the course content and our exceptional service. 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Register today for the GPCR Drug Discovery Conference and save $200 with discount code “ DRGPCR24 ”. 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23-25, 2024 Engage with your peers and delve into the latest developments in adhesion GPCR biology. The full agenda is now available; check it here ! If you want to enhance your brand, email Hello@DrGPCR.com  for sponsorship opportunities. Classified GPCR News  Let’s dive into the   Classified GPCR News from September 9th to 15th, 2024 Industry News MBX aims for $136M IPO to take potential rival to Ascendis' Yorvipath into phase 3 Certa Therapeutics Announces International Non-Proprietary Name for its First-in-class GPR68 Inhibitor Asengeprast (FT011) AlphaProteo generates novel proteins for biology and health research Innovate UK announced the winners of its Transforming Cancer Therapeutics grant, which focuses on developing life-changing cancer treatments. 𝗦𝘂𝗺𝗺𝗮𝗿𝘆 𝗼𝗳 𝘁𝗵𝗲 𝗿𝗲𝘀𝘂𝗹𝘁𝘀 𝗼𝗳 𝗔𝗘𝗙𝟬𝟭𝟭𝟳 𝗣𝗵𝗮𝘀𝗲 𝟮𝗯 𝗶𝗻 𝗖𝗨𝗗 Nxera Pharma’s Partner Centessa Announces Positive Interim Phase 1 Clinical Data with its Novel Orexin Receptor 2 (OX2R) Agonist, ORX750, in Acutely Sleep-Deprived Healthy Volunteers Cumulus raising $50M, spinning GPR68 small molecules into GIO New treatments being developed for schizophrenia Crinetics Pharmaceuticals Announces September 2024 Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery September 22, 2024 | Biomolecular Horizons 2024 September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   NEW November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan HIGHLIGHT Postdoc in Molecular Pharmacology - The Hauser Group NEW Postdoctoral Scholar – iPSC in cardiac and endothelial cell function NEW Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Adhesion GPCRs Loss of cardiomyocyte-specific Adhesion G Protein Coupled Receptor G1 (ADGRG1/GPR56) promotes pressure overload-induced heart failure GPCR Activation and Signaling Positive allosteric modulation of a GPCR ternary complex GPCR Binders, Drugs, and more Progress on the development of Class A GPCR-biased ligands GPCRs in Cardiology, Endocrinology, and Taste CRTC1 in Mc4r-expressing cells is required for peripheral metabolism and systemic energy homeostasis Eiken syndrome with parathyroid hormone resistance due to a novel parathyroid hormone receptor type 1 mutation: clinical features and functional analysis GPCRs in Neuroscience Gain control of sensory input across polysynaptic circuitries in mouse visual cortex by a single G protein-coupled receptor type (5-HT2A) GPCRs in Oncology and Immunology The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy GPR97 depletion aggravates imiquimod-induced psoriasis pathogenesis via amplifying IL-23/IL-17 axis signal pathway Structural and Molecular Insights into GPCR Function Exploring the constitutive activation mechanism of the class A orphan GPR20 Become a Premium Member! 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Hello GPCR Enthusiasts, Dive into this week's exciting updates on cutting-edge GPCR research, new learning opportunities, and industry news! Don't miss out—explore, learn, and elevate your expertise today! Weekly Highlights: Congrats to: Daniel Matúš , Simone Prömel , et al., for their work on The N terminus-only (trans) function of the Adhesion GPCR Latrophilin-1 controls multiple processes in reproduction of C. elegans Alexei Sirbu , Paolo Annibale , et al., for their study on Cell swelling enhances ligand-driven β-adrenergic signaling ✨ Reserve Your seat before these fill up! Our updated course schedule is designed to fit seamlessly into your routine, offering an enriched learning experience. Every Thursday at 10 AM EST: Principles of Pharmacology I October 3, 10, 17, 24 (four sessions) Topics: Pharmacologic activity measurement, mechanisms of action, and GPCR discovery strategies. Principles of Pharmacology II October 31, November 7, 14, 21, December 5 (five sessions) (we skipped Thanksgiving, of course!) Topics: New cellular assays, real-time kinetics, and unique GPCR behaviors. 🔥 Why You Should Enroll Now: Act Fast & Save Big! The Principles of Pharmacology I & II BUNDLE is your key to mastering the field. You can embrace a  25% OFF early bird discount as a premium member . But act fast – this offer is only available for a limited time. Not a premium member yet? No problem – we offer a 5-day FREE trial! And access over 500 minutes of recorded classes in our  GPCR courses with Drs. Terry Kenakin and Sam Hoare ! Affordable & Unique Learning Experience Our budget-friendly courses offer a unique approach to mastering pharmacology. Flexible Learning Rewatch sessions anytime to reinforce your learning. Our Students Love Us! Past students rave about the content and service of our courses. Join us for an exciting discussion with Dr. Terry Kenakin as he shares insights into what you can anticipate for the upcoming courses. Don't miss this fantastic opportunity to gain valuable knowledge and prepare for the forthcoming sessions! Exclusive Deal for Scientists Residing and Working in Developing Nations If you live and work  in a developing country, please complete this form to enjoy complimentary access to Dr. Kenakin's upcoming courses. Our goal is to ensure that education is within reach for everyone! Secure your spot today and dive into the evolving world of GPCRs! GPCR Event Spotlight Discovery on Target’s 19th Annual GPCR-Based Drug Discovery Targeting G Protein-Coupled Receptors for New Therapeutic Options 📍  Boston, MA 📅 October 2 -3, 2024 Join top researchers to explore the latest in GPCR-targeted drug design, including machine learning, new biophysical techniques, and medicinal chemistry. Register today for the GPCR Drug Discovery Conference and save $200 with discount code “ DRGPCR24 ”. 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23-25, 2024 Connect with your colleagues and immerse yourself in the most recent advancements in adhesion GPCR biology. Stay tuned for the release of the full agenda! Are you interested in boosting your brand? Contact us at Hello@DrGPCR.com  for sponsorship opportunities. Classified GPCR News  Let’s dive into the   Classified GPCR News from September 2nd to 8th, 2024 Industry News Superluminal Medicines Closes $120 Million Series A Round Domain Therapeutics has been nominated for Prix Galien USA Carterra unveils its most sensitive biosensor platform; Carterra Ultra™ ushers in a new frontier in fragment and small molecule drug discovery Is the pharma community looking hard enough before trying to engage highly challenging neurology targets? Engaging multiple sclerosis by drugging a “simple” GPCR. This technique for studying cell receptors could have sweeping implications for drug development DeepCure team is excited to welcome Justin Potnick, to our Medicinal Chemistry group Call for GPCR Papers Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery NEW September 22, 2024 | Biomolecular Horizons 2024 September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   NEW November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan HIGHLIGHT Postdoc in Molecular Pharmacology - The Hauser Group Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Adhesion GPCRs The N terminus-only (trans) function of the Adhesion GPCR Latrophilin-1 controls multiple processes in reproduction of C. elegans The G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH Signaling GPCR Activation and Signaling Illuminating GPCR trafficking Cell swelling enhances ligand-driven β-adrenergic signaling Roles of the gate loop in β-arrestin-1 conformational dynamics and phosphorylated receptor interaction Early Events in β2AR Dimer Dynamics Mediated by Activation-Related Microswitches Nuclear translocation of the membrane oxoeicosanoid/androgen receptor, OXER1: Possible mechanisms involved An engineered trafficking biosensor reveals a role for DNAJC13 in DOR downregulation GPCRs in Cardiology, Endocrinology, and Taste Role of G protein coupled receptors in acute kidney injury Ligand-Dependent and G Protein-Dependent Properties for the Sweet Taste Heterodimer, TAS1R2/1R3 GPCRs in Neuroscience GPCR-Mediated Natural Products and Compounds: Potential Therapeutic Targets for the Treatment of Neurological Disease s Activation of GPR55 alleviates neuropathic pain and chronic inflammation Developmental exposures to common environmental pollutants result in long-term Reprogramming of hypothalamic-pituitary axis in mice GPCRs in Oncology and Immunology A disturbed metabolite-GPCR axis is associated with microbial dysbiosis in IBD patients: Potential role of GPR109A in macrophages Structural and Molecular Insights into GPCR Function Insights into the structure and activation mechanism of some class B1 GPCR family members Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation Become a Premium Member! 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Significant advancements in the cellular biology of G protein-coupled receptors (GPCRs) about a novel biosensor shed light on the endosomal proteome associated with the δ-opioid receptor (DOR). This study, published in Nature Chemical Biology, highlights the role of the chaperone protein DNAJC13 in the endosomal-lysosomal pathway for DOR. The research team, led by Brandon Novy and colleagues, utilized an innovative APEX2/AUR biosensor that allows scientists to monitor the agonist-induced trafficking of DOR to the lysosome with high precision. By employing this biosensor, the research team identified 492 genes that significantly influence DOR function, with DNAJC13 emerging as a standout candidate along with WDR91 and SNX24. The findings suggest that DNAJC13 is crucial to the trafficking of DOR, facilitating its downregulation and influencing cellular signaling pathways essential for pain and anxiety regulation. How does this new biosensor work? The critical player is Apurinic/Apyrimidinic Endodeoxyribonuclease 2 (APEX2). APEX2 is a peroxidase enzyme that catalyzes the oxidation of specific substrates in the presence of hydrogen peroxide (H 2 O 2 ). Therefore, it’s a great molecular tool for proximity labeling approaches in living cells.  In this study, the DOR receptor was genetically fused to APEX2, creating a DOR-APEX2 construct. Upon agonist activation, the DOR-APEX2 complex is internalized and trafficked to the lysosome. During this process, APEX2 can label proteins in the vicinity, allowing the capture of a snapshot of the endosomal proteome associated with the DOR receptor. APEX2 biosensor utilizes a fluorogenic substrate called Amplex UltraRed (AUR). When AUR is oxidized by APEX2 in the presence of H 2 O 2 , it produces a fluorescent product that can be detected and quantified. This fluorescence serves as a readout for the activity of APEX2 and, by extension, the trafficking of the GPCR of interest. After the labeling reaction, the researchers purified and biotinylated proteins (those that have been labeled by APEX2) and analyzed them using quantitative proteomics such as tandem mass tags. Finally, this analysis provided insights into the molecular composition of the endosomal environment and the proteins involved in the trafficking of the DORs. The development of molecular tools to study GPCR trafficking in real-time opens new avenues for understanding drug tolerance and resistance, particularly in the context of opioid therapies. As the opioid crisis continues to challenge public health, insights gained from this research could inform the development of safer analgesics that minimize the risk of addiction while maintaining their efficacy. The implications of this research extend beyond basic science ; understanding the role of DNAJC13 in GPCR trafficking could profoundly affect the development of therapeutic strategies for conditions related to other GPCR-mediated pathways. As the field continues to evolve, this study represents a crucial step toward unraveling the understanding of GPCR regulation and its potential to revolutionize human health. For further details, refer to the full article: DOI: 10.1038/s41589-024-01705-2

Hello GPCR Community, Stay up-to-date with the latest GPCR research, including breakthrough studies, upcoming events, and our newly announced pharmacology courses. Don't miss exclusive discounts, expert insights, and opportunities to elevate your learning with our tailored programs. Secure your spot today and dive into the evolving world of GPCRs! This week's highlights include congrats to: Bruce Allen , Terence Hébert , et al. for their work on Understanding the impact of nuclear-localized GPCRs on cellular signaling. Lukas Grätz , Jan Voss , and Gunnar Schulte , for their study on Class-Wide Analysis of Frizzled-Dishevelled Interactions Using BRET Biosensors Reveals Functional Differences among Receptor Paralogs . Małgorzata Kogut-Günthel , Antonella Di Pizio , et al. for their research on The path to the G protein-coupled receptor structural landscape: Major milestones and future directions . 🎉 New Course Dates Announced: Don’t Miss Out! Our refreshed schedule is designed to fit seamlessly into your calendar and enhance your learning experience. Every Thursday at 10 AM EST: Principles of Pharmacology I October 3, 10, 17, 24 (four sessions) Explore pharmacologic activity measurement, mechanisms of action, and GPCR discovery strategies. Principles of Pharmacology II October 31, November 7, 14, 21, December 5 (five sessions) (we skipped Thanksgiving, of course!) Delve into new cellular assays, real-time kinetics, and unique GPCR behaviors. 🔥 Why You Should Enroll Now: Act Fast & Save Big! The Principles of Pharmacology I & II BUNDLE is your golden ticket to mastering the field. Premium members can enjoy a 25% OFF early bird discount , but hurry - it's only available for a limited time. Not a premium member yet? Don't worry - we offer a 5-day FREE trial! Plus, access to over 500 minutes of recorded classes of our GPCR Courses with Drs. Terry Kenakin and Sam Hoare ! Affordable & Unique Learning Experience Dive deep into pharmacology with our budget-friendly courses that offer a unique approach to understanding the field. Rewatch Anytime Enjoy the flexibility of rewatching sessions at your convenience to reinforce your learning. Don't miss out on our fantastic discussion with Dr. Terry Kenakin on what to anticipate for these courses! Special Offer for Scientists who work and live in developing countries If you live and work in a developing country, please fill out this form to receive complimentary access to Dr. Kenakin's upcoming classes. We’re committed to making education accessible to all! Secure your spot today and elevate your pharmacology expertise! Don’t miss this chance to benefit from our early bird pricing and premium content. GPCR Event Spotlight Discovery on Target’s 19th Annual GPCR-Based Drug Discovery Targeting G Protein-Coupled Receptors for New Therapeutic Options 📍  Boston, MA 📅 October 2 -3, 2024 GPCRs, among the most ancient and complex drug targets, remain central in modern targeted drug discovery. The 19th Annual GPCR-Based Drug Discovery conference (October 2-3, 2024, in Boston and online) gathers top researchers to explore the latest advances in designing precise GPCR-targeted drugs, including the role of machine learning, new biophysical techniques, and medicinal chemistry approaches in understanding these challenging receptors. Join us October 2-3 at the GPCR Drug Discovery Conference . Register today and save $200 off the current rate. Use discount code “ DRGPCR24 ” to save. 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23-25, 2024 Join us to connect with peers and explore the latest in adhesion GPCR biology. Full Agenda Coming Soon! Are you interested in boosting your brand? Contact us at Hello@DrGPCR.com  for sponsorship opportunities. Classified GPCR News  Let’s dive into the   Classified GPCR News from August 26th to September 1st, 2024 Industry News GPCR-RAMP Interactome Maps Could Help Drug Developers Find Buried Treasures Edelris Announces Research Services Agreement with Pfizer on Targeted Protein Degradation Modalities A quick revision of how β-adrenergic receptors work and how their antagonists can achieve therapeutic outcomes. Domain Nominated for Prestigious Prix Galien USA ‘Best Startup’ Award: Pioneering GPCR-Driven Immunotherapies in Cancer Treatment Structure Therapeutics Appoints Angus C. Russell to Board of Directors Adiso Announces Groundbreaking Research Highlighting ADS024 a Novel Oral Agent for Neuroinflammation Call for GPCR Papers Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan NEW   Postdoc in Molecular Pharmacology - The Hauser Group NEW Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Senior or Lead Researcher   GPCR Activation and Signaling Profiling the proximal proteome of the activated μ-opioid receptor Understanding the impact of nuclear-localized GPCRs on cellular signalling GRK2 is critical for the cleavage of the porcine embryo by regulating HSP90 and the AKT pathway Structural basis for CCR6 modulation by allosteric antagonists Class-Wide Analysis of Frizzled-Dishevelled Interactions Using BRET Biosensors Reveals Functional Differences among Receptor Paralogs GPCRs in Neuroscience Opposing GPCR signaling programs protein intake setpoint in Drosophila Kappa Opioid Receptor Activation Induces Epigenetic Silencing of Brain-Derived Neurotropic Factor via HDAC5 in Depression GPCRs in Oncology and Immunology Structural Basis for the Recognition of GPRC5D by Talquetamab, a Bispecific Antibody for Multiple Myeloma Identification of Small-Molecule Antagonists Targeting the Growth Hormone Releasing Hormone Receptor (GHRHR) Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes Methods & Updates in GPCR Research A nondestructive membrane engineering method using an amphiphilic polymer Labeling of CC Chemokine Receptor 2 with a Versatile Intracellular Allosteric Probe Selective optogenetic inhibition of Gαq or Gαi signaling by minimal RGS domains disrupts circuit functionality and circuit formation Reviews, GPCRs, and more G Protein-Coupled Receptors in Skin Aging The path to the G protein-coupled receptor structural landscape: Major milestones and future directions Going rogue: mechanisms, regulation, and roles of mutationally activated Gα in human cancer Structural and Molecular Insights into GPCR Function Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5 Altered O-glycosylation of β1-adrenergic receptor N-terminal single-nucleotide variants modulates receptor processing and functional activity Differential pathogenetic mechanisms of mutations in helix 2 and helix 6 of rhodopsin Become a Premium Member! 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“ A substitution of one amino acid by another in a protein can have effects ranging from negligible to dramatic, either locally or distantly .” (Bikker et al., 1998) Quantitative studies of how drugs modulate their targets have been instrumental in discovering new treatments. A rational drug discovery campaign hinges on a deep understanding of how distinct molecules interact with receptors at the molecular level. Fortunately, several techniques and methodologies have been developed to support this process. Notably, innovations in structural biology, such as X-ray crystallography and cryo-electron microscopy, have successfully elucidated ligand-receptor interactions. For example, Carlsson et al. (2010) utilised structural information and virtual ligand screening to discover novel ligands for the A 2A  adenosine receptor. While these structural techniques offer significant advantages in drug discovery, no single method can fully capture the impact of residue alterations on ligand function and ligand-receptor interactions. But why is this information crucial?  Kosar et al. (2024) addressed this question by using the role of the Trp258 6.48 residue to guide and explain the discovery of a novel inverse agonist at the cannabinoid receptor 2. Furthermore, data on the role of specific residues within receptors can provide valuable insights for structure-activity relationship (SAR) studies, informing the development of ligands tailored to exploit available binding pocket space. In this context, mutagenesis has emerged as an "old-school" but essential technology to fill these knowledge gaps. Mutagenesis involves deliberately altering the DNA sequence of a gene to study the resulting changes in protein function. Through either random or targeted (site-directed) approaches, mutagenesis can provide a comprehensive understanding of how drugs interact with different receptor regions and link these interactions to functional variations. This technique has uncovered fundamental aspects of the G protein-coupled receptor (GPCR) function, including specific ligand interactions, such as those at the adenosine A 1  adenosine receptor (Nguyen et al., 2016). While advancements in site-directed technology have largely supplanted random mutagenesis, the latter has seen a resurgence in recent times for exploratory analyses to identify previously unknown regions critical to GPCR function. For example, random mutagenesis, combined with novel specificity high-throughput selection, has been used to identify specificity-determining positions without prior knowledge of structure or sequence homology (Di Roberto et al., 2017). However, several challenges have limited the use of mutagenesis in drug discovery. Targeted mutagenesis may miss broader functional regions, while random mutagenesis generates extensive data that require labour-intensive screening. Furthermore, probing species- or subtype-selectivity introduces complexities due to the differing contexts of receptor subtypes across species. Integrating mutagenesis data with computational models also presents challenges, requiring high-quality data and robust algorithms. Moreover, these studies are resource-intensive, necessitating significant investments in technology and infrastructure. To overcome these challenges, future directions include developing high-throughput techniques, better integrating experimental and computational methods, and improving frameworks for data interpretation. Advances in bioinformatics and machine learning will play a pivotal role in addressing these obstacles, enhancing our understanding of GPCR structure and function. For instance, Heydenreich et al. (2023) developed a data science framework that combined mutagenesis and structural data to contextualise ligand-induced structural changes and reveal the principles underlying efficacy and potency. Additionally, deep mutational scanning can generate large-scale datasets, allowing researchers to determine the functional consequences of every possible amino acid change at each position in a protein, as well as the biochemical activity of hundreds of thousands of protein variants (Fowler and Fields, 2014). In summary, mutagenesis can be a critical tool in drug discovery, particularly for studying GPCRs. While advancements in structural biology techniques like X-ray crystallography and cryo-electron microscopy have deepened our understanding of ligand-receptor interactions, mutagenesis fills crucial knowledge gaps by revealing how specific amino acid changes impact receptor function. Despite its significant contributions, challenges such as data complexity, resource intensity, and integration with computational models remain. Future advancements, including high-throughput techniques and bioinformatics integration, will further enhance the utility of mutagenesis in drug discovery. Reference   Bikker, J. A., Trumpp-Kallmeyer, S., & Humblet, C. (1998). G-protein coupled receptors: models, mutagenesis, and drug design. Journal of Medicinal Chemistry , 41 (16), 2911-2927. Carlsson, J., Yoo, L., Gao, Z. G., Irwin, J. J., Shoichet, B. K., & Jacobson, K. A. (2010). Structure-based discovery of A2A adenosine receptor ligands. Journal of Medicinal Chemistry , 53 (9), 3748-3755. Di Roberto, R. B., Chang, B., & Peisajovich, S. G. (2017). The directed evolution of ligand specificity in a GPCR and the unequal contributions of efficacy and affinity. Scientific Reports , 7 (1), 16012. Fowler, D. M., & Fields, S. (2014). Deep mutational scanning: a new style of protein science. Nature Methods , 11 (8), 801-807. Heydenreich, F. M., Marti-Solano, M., Sandhu, M., Kobilka, B. K., Bouvier, M., & Babu, M. M. (2023). Molecular determinants of ligand efficacy and potency in GPCR signaling. Science , 382 (6677), eadh1859. Kosar, M., Sarott, R. C., Sykes, D. A., Viray, A. E., Vitale, R. M., Tomašević, N., ... & Carreira, E. M. (2024). Flipping the GPCR switch: Structure-based development of selective cannabinoid receptor 2 inverse agonists. ACS Central Science , 10 (5), 956-968. Nguyen, A. T., Baltos, J.-A., Thomas, T., Nguyen, T. D., Muñoz, L. L., Gregory, K. J., White, P. J., Sexton, P. M., Christopoulos, A., & May, L. T. (2016). Extracellular loop 2 of the adenosine A1 receptor has a key role in orthosteric ligand affinity and agonist efficacy. Molecular Pharmacology ,  90 (6), 703-714.

Dear GPCR Enthusiasts , Get ready for an exciting learning experience with our newly updated Principles of Pharmacology I & II  courses! We've refreshed the schedule and can’t wait for you to join us on these new dates. New Course Dates: Principles of Pharmacology I :  October 3, 10, 17, 24 (four sessions) Principles of Pharmacology II :  October 31, November 7, 14, 21, December 5 (five sessions) Courses Highlights Act Fast: Don’t miss this incredible opportunity to immerse yourself in the  Principles of Pharmacology I & II BUNDLE . Grab this chance to deepen your understanding of pharmacology and take your knowledge to the next level! Secure your spot today and elevate your expertise! Premium members enjoy a 5-day free trial—join now and save with the 25% OFF early bird discount . Enrollment is now open to the public! Topics include pharmacologic activity measurement, mechanisms of action, and GPCR discovery strategies. Take advantage of a 25% early bird discount for premium members! Topics cover new cellular assays, real-time kinetics, and unique GPCR behaviors. Secure your spot now by signing up today! Did you know...? As a  premium member , you can access over 500 minutes of exclusive, expert-led content from esteemed leaders, Drs. Kenakin and Hoare . We highly recommend exploring valuable resources such as ' Applying Pharmacology to Drug Discovery ' and ' Advanced Data Analysis for GPCR Pharmacology' ." GPCR Event Spotlight    11th Adhesion GPCR Workshop    Location:  Mexico City Dates:  October 23-25, 2024 Connect with peers and delve into cutting-edge adhesion GPCR biology. Interested in boosting your brand? Reach out to us at Hello@DrGPCR.com for sponsorship opportunities .  Let’s dive into the   Classified GPCR News  from August 19th to 25th, 2024 GPCR Activation and Signaling Homodimerization of CB2 cannabinoid receptor triggered by a bivalent ligand enhances cellular signaling GPCR Binders, Drugs, and more Selenomethionine Promotes Milk Protein and Fat Synthesis and Proliferation of Mammary Epithelial Cells through the GPR37-mTOR-S6K1 Signaling GPCRs in Neuroscience Astrocyte Gi-GPCR signaling corrects compulsive-like grooming and anxiety-related behaviors in Sapap3 knockout mice Methods & Updates in GPCR Research Genome-wide identification of 769 G protein-coupled receptor (GPCR) genes from the marine medaka Oryzias melastigma Industry News Cumulus Oncology and leadXpro Achieve Critical Milestone in GPR68 Drug Discovery Project Ambrosia lands $16m to ‘improve on existing GLP-1 drugs’ Opening Ceremony of Xuzhou Zhongshu Research Site and CNS Drug Innovation Forum Nxera Pharma Notes Positive Phase 2 Data for Partnered Schizophrenia Candidate NBI-1117568 Call for GPCR Papers NEW Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery NEW September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs NEW Research Associate Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Senior or Lead Researcher   Become a Premium Member! Get your 5-day free trial TODAY!

Dear GPCR Community, Before diving into this week's news, prepare for an incredible learning journey! We’ve made some updates to the Principles of Pharmacology I & II courses, and we can’t wait for you to join us on these new dates. Here’s the refreshed schedule: Principles of Pharmacology I October 3, 10, 17, 24 Principles of Pharmacology II October 31 November 7, 14, 21 December 5 As a premium member , you’re also unlocking over 500 minutes of exclusive, expert-led content from thought leaders like Drs. Kenakin and Hoare. Don’t miss out on insightful resources like '   Applying Pharmacology to Drug Discovery ' and ' Advanced Data Analysis for GPCR Pharmacology .' We’re thrilled to have you with us on this learning journey! Courses Highlights The clock is ticking!  Don’t miss your chance to dive into the Principles of Pharmacology I & II BUNDLE . Grab your spot today and score a 25% early bird discount—exclusively for premium members. Register now and level up your expertise! Become a premium member today and enjoy a 5-day free trial. Enrollment:  Open to the Public Now! Dates:  October 3 to 24, 2024 (four sessions) Topics:  Measuring pharmacologic activity, mechanisms of action, and GPCR discovery strategies. Discount:  25% off for Premium Members—Act Fast! Dates:  October 31, November 7 - 14 -21, and December 5, 2024 (five sessions) Topics:  New cellular assays, real-time kinetics, and discovering unique GPCR behaviors. Sign up today to secure your spot! GPCR Event Spotlight    11th Adhesion GPCR Workshop    Location:  Mexico City Dates:  October 23-25, 2024 Join us  to connect with peers and explore cutting-edge adhesion GPCR biology. Don't miss the chance to boost your brand's presence at this exclusive event. Contact us at Hello@DrGPCR.com  to discover exciting sponsorship opportunities . This week's highlight includes congrats to: Madison Walker , Benjamin Myers , et al., for their research on GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade Elita Yuliantie , Arthur Christopoulos , Patrick M. Sexton , Denise Wootten , et al., for their work on Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs  Let’s dive into the   Classified GPCR News  from August 12th to 18th, 2024 Adhesion GPCRs Heterogeneity of tethered agonist signaling in adhesion G protein-coupled receptors GPCR Activation and Signaling A-Kinase-Anchoring-Protein Subtypes Differentially Regulate GPCR Signaling and Function in Human Airway Smooth Muscle GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade Allatotropin (AT) related peptides L-ATRP and D2-ATRP diastereomers activate an endogenous receptor and suppress heart rate in the Pacific abalone Haliotis discus hannai GPCR Binders, Drugs, and more Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs GPCRs in Cardiology, Endocrinology, and Taste Regulator of G-protein signaling expression in human intestinal enteroendocrine cells and potential role in satiety hormone secretion in health and obesity GPCRs in Neuroscience Light and dopamine impact two circadian neurons to promote morning wakefulness LPA3 agonist-producing Bacillus velezensis ADS024 is efficacious in multiple neuroinflammatory disease models Discovery of a potent melatonin-based inhibitor of quinone reductase-2 with neuroprotective and neurogenic properties GPCRs in Oncology and Immunology Chemoattractant receptor signaling in humoral immunity Methods & Updates in GPCR Research Probing PAC1 receptor activation across species with an engineered sensor A Multi-Angle Approach to Predict Peptide-GPCR Complexes: The N/OFQ-NOP System as a Successful AlphaFold Application Case Study Constitutive and Conditional Epitope Tagging of Endogenous G-Protein-Coupled Receptors in Drosophila Measuring G protein activation by spectrally resolved imaging fluorescence fluctuation spectroscopy Structural and Molecular Insights into GPCR Function Monitoring GPCR conformation with GFP-inspired dyes Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy Industry News Crinetics Pharmaceuticals Announces August 2024 Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Unlocking New Possibilities in GLP-1R Drug Discovery GPCR Events, Meetings, and Webinars September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Senior or Lead Researcher   Senior Scientist, Cryo-Electron Microscopy   Postdoctoral Research Associate Become a Premium Member! 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Dear GPCR Enthusiasts! Get ready to save the dates! Dr. GPCR University offers two live courses this fall that you won’t want to miss. Before the new semester kicks off, dive into our premium on-demand courses! With your membership, you’ll access over 500 minutes of top-notch content from Drs. Kenakin and Hoare on '   Applying Pharmacology to Drug Discovery ' and ' Advanced Data Analysis for GPCR Pharmacology .' Choose between our monthly or yearly plans (with a 5-day free trial) to enjoy these courses and snag 25% off early bird discounts on upcoming classes. Check out what’s coming in September and October: Sign up for both courses now and score a 25% early bird discount with a premium membership! Course Details: When:  Thursdays at 10 AM EST Format:  Engaging Online Lectures with access to pre-read materials. Perks Include: In-depth Reading Materials Access to a Private Community Certificate of Participation for each course Don’t miss out—grab this special offer today! s Check out the details of each course below: Open to the Public: Enrollment is Now Available! Hurry and secure your spot TODAY! Dates:  September 5 to 26, 2024 What You’ll Learn during the four sessions: How to measure pharmacologic activity of ligands (affinity, efficacy, co-operativity) Determining mechanisms of action for new GPCR ligands Key elements of a comprehensive and effective GPCR discovery strategy Exclusive 25% Early Bird Discount for Dr. GPCR Ecosysme Premium members. Secure your spot before public enrollment opens! Dates:  October 3 to 31, 2024 What You’ll Master during the five sessions: Utilizing new cellular assays to analyze GPCR ligand behavior Predicting activity and in vivo target coverage with real-time kinetics Discovering new ligands and unique GPCR behaviors for innovative drug profiles GPCR Event Highlight  11th Adhesion GPCR Workshop    Location : Mexico City Dates : October 23-25, 2024 Join us in the vibrant heart of Mexico City to connect with fellow scientists and delve into the latest advances in adhesion GPCR biology. Logo Contest : Let your creativity shine! Submit your design for our Logo Contest by August 15, 2024 (Yes, it's TODAY)! Sponsorship Opportunities : Elevate your brand’s visibility at this prestigious event. Contact us at Hello@DrGPCR.com to explore sponsorship options. Your participation is eagerly awaited! This week's highlight includes congrats to: Miles Thompson ,   Alexander Hauser ,   Caroline Gorvin ,   et al.   for their work on GPCR pharmacogenomics  Let’s dive into the   Classified GPCR News  from August 5th to 11th, 2024 GPCR Activation and Signaling Pharmacological characterization of the zebrafish Hrh2a histamine H2 receptor Revealing the graded activation mechanism of neurotensin receptor 1 Intracellular pathways of calcitonin gene-related peptide-induced relaxation of human coronary arteries: A key role for Gβγ subunit instead of cAMP Olanzapine manipulates neuroactive signals and may onset metabolic disturbances GPCR Binders, Drugs, and more Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors GPCRs in Neuroscience In-silico predicted mouse melanopsins with blue spectral shifts deliver efficient subcellular signaling Striatal serotonin release signals reward value Ciliary length variations impact cilia-mediated signaling and biological responses The receptor tyrosine kinase IGF1R and its associated GPCRs are co-regulated by the noncoding RNA NEAT1 in Alzheimer's disease Nanoplastic at environmentally relevant concentrations induces toxicity across multiple generations associated with inhibition in germline G protein-coupled receptor CED-1 in Caenorhabditis elegans Calcium-sensing receptor regulates Kv7 channels via Gi/o protein signalling and modulates excitability of human induced pluripotent stem cell-derived nociceptive-like neurons Methods & Updates in GPCR Research G protein-coupled receptor (GPCR) pharmacogenomics Visualization of endogenous G proteins on endosomes and other organelles Reviews, GPCRs, and more Phytocannabinoids in neuromodulation: From omics to epigenetics The impact of nanobodies on GPCR structural biology and their potential as therapeutic agents Industry News Nxera Pharma Operational Highlights and Consolidated Results for the Second Quarter and First Half 2024 Cracking Codes in Cellular Communication Neurocrine Biosciences to Present at the Canaccord Genuity 44th Annual Growth Conference GPCR drugs make up a third of the market! GPCRs and mRNA antigens enable drug discovery and development Mapping GPCR-RAMP complexes with MolBoolean Screening GPR75 Modulators Using Medium-Throughput Reporter Gene Assay GPCR Therapeutics Optimizes the Joint Development of New Drugs Using Intralinks’ Virtual Data Room   GPCR Events, Meetings, and Webinars NEW September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Senior or Lead Researcher   Senior Scientist, Cryo-Electron Microscopy   Postdoctoral Research Associate Become a Premium Member! Get your 5-day free trial TODAY!

Hey there, readers! Take a look at our GPCR coverage for this week. We've got 11 GPCR papers, seven industry news pieces, a new GPCR event, and even a job ad.   This week's highlight includes congrats to: Miles Thompson , Alexander Hauser , Caroline Gorvin ,   et al.   for their work on GPCR gene variants and human genetic disease Ilana Kotliar , Thomas Sakmar , et al. for their study on Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins Nicholas Kapolka , Geoffrey Taghon , and Daniel Isom  for their research on Advances in yeast synthetic biology for human GPCR biology and pharmacology Dr. GPCR University Early-Bird Registration Open for Premium Members! Unlock a 25% exclusive discount on these courses with Dr. Terry Kenakin with our premium membership and enjoy a 1-month FREE trial! Don’t miss out—secure your spot today! Registrations for the public will be on Monday! Hurry! Courses Schedule and  Benefits Every Thursday at 10 am EST Online Lectures 1:1 meeting with Dr. Terry Kenakin Reading Materials Access to the private group Certificate of participation Learn the essentials: Measuring the pharmacologic activity of ligands (affinity, efficacy, co-operativity) Determining mechanisms of action for new GPCR ligands Elements of a comprehensive and effective GPCR discovery Master advanced applications: Using new cellular assays to analyze GPCR ligand behavior Predicting activity and in vivo target coverage with real-time kinetics Discovering new ligands and GPCR behaviors for unique drug profiles   GPCR Event Highlight 11th Adhesion GPCR Workshop Join us in vibrant Mexico City from October 23-25, 2024, to connect with fellow scientists and explore the latest in adhesion GPCR biology. Logo Contest : Let your creativity shine by submitting your design for the Logo Contest before August 15, 2024 Sponsorship Opportunities :   Elevate your brand's presence at this scientific event . Contact us at Hello@DrGPCR.com   to learn more. Your participation is eagerly awaited!  Let’s dive into the   Classified GPCR News  from July 29th to August 4th, 2024 GPCR Activation and Signaling ONE-GO: Direct detection of context-dependent GPCR activity Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins Molecular mechanism of bitter taste receptor agonist-mediated relaxation of airway smooth muscle GPCR Binders, Drugs, and more Expanding Structure-Activity Relationships of Human Urotensin II Peptide Analogues: A Proposed Key Role of the N-Terminal Region for Novel Urotensin II Receptor Modulators GPCRs in Oncology and Immunology G protein-coupled receptor-mediated signaling of immunomodulation in tumor progression Methods & Updates in GPCR Research GPCR Signaling: A Study of the Interplay Between Structure, Energy, and Function Engineering a GPCR-based yeast biosensor for a highly sensitive melatonin detection from fermented beverages The calcium-binding photoprotein clytin II: Expression of the preferred human codon-optimized clytin II gene in Chinese hamster ovary-K1 cells and its use in the G-protein-coupled receptor assays Predicting the Hallucinogenic Potential of Molecules Using Artificial Intelligence Reviews, GPCRs, and more G protein-coupled receptor (GPCR) gene variants and human genetic disease Advances in yeast synthetic biology for human G protein-coupled receptor biology and pharmacology Industry News Muscarinic drugs breathe new life into schizophrenia pipeline GPCR Dynamics Reveal Mechanisms for Drug Discovery DMS: Linking Protein Structure To Function AbbVie Completes Acquisition of Cerevel Therapeutics Nxera Pharma attended the Drug Discovery Ecosystem Summit Tectonic Therapeutic Announces Closing of Merger with AVROBIO as well as Concurrent Private Placement of $130.7 Million Tectonic Therapeutic Announces US IND Clearance for Lead Program, TX45   GPCR Events, Meetings, and Webinars September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry NEW October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs NEW Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Senior or Lead Researcher   Senior Scientist, Cryo-Electron Microscopy   Postdoctoral Research Associate Join Dr. GPCR Ecosystem

📰 GPCR Weekly News, July 22 to 28, 2024 In the fast-paced world of pharmaceuticals and drug discovery, it is crucial for professionals to stay informed about the latest advancements and breakthroughs. We have 18 GPCR papers, four industry news articles, and two job ads. This week's highlight includes congrats to: Clementine E Philibert and Mikel Garcia-Marcos   for their work on Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators András D Tóth , Gábor Turu , and László Hunyady  for their research on Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors Antonios Drakopoulos , Peter Gmeiner , Davide Calebiro , Michael Decker , et al. for their study on Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors Dr. GPCR University Early-Bird Registration Now Open for Premium Members! We’re thrilled to announce our upcoming courses with Dr. Terry Kenakin ! Get your premium membership  and enjoy a 25% exclusive discount (1 month FREE trial!) . Don’t miss out—secure your spot today! Courses Schedule and Benefits Every Thursday at 10 am EST Online Lectures 1:1 meeting with Dr. Terry Kenakin Reading Materials Access to the private group Certificate Explore: Key metrics for assessing ligand pharmacology (affinity, efficacy, co-operativity) Mechanisms of action for new GPCR ligands Essentials for effective GPCR discovery Discover: Advanced cellular assays for GPCR ligand behavior Real-time kinetics for predicting activity Unique drug profiles from new ligands and GPCR behaviors GPCR Event Highlight Join us in vibrant Mexico City from October 23-25, 2024, for the 11th Adhesion GPCR Workshop ! Connect with fellow scientists and dive into the latest in adhesion GPCR biology. Logo Contest : Submit your design by August 15, 2024, to have your artwork featured at the event. Sponsorship Opportunities :   Boost your brand’s visibility at this scientific event. Contact us at Hello@DrGPCR.com  to learn more. We look forward to your participation! Let’s dive into the   Classified GPCR News  from July 22 to 28, 2024 GPCR Activation and Signaling Activating an invertebrate bistable opsin with the all-trans 6.11 retinal analog Comparison of the Genomic Activity of an EP4-Receptor and β2-Adrenoceptor Agonist in BEAS-2B Human Bronchial Epithelial Cells: In Search of Compartmentalized, cAMP-dependent Gene Expression Ligand bias at the muscarinic acetylcholine receptor family: opportunities and challenges Modulating Vertebrate Physiology by Genomic Fine-Tuning of GPCR Functions Smooth operator(s): dialing up and down neurotransmitter responses by G-protein regulators Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors Inverse Regulation of C-C Chemokine Receptor 3 Oligomerization by Downstream Proteins Indicates Biased Signal Transduction Pathways Activation of a GPCR, ORL1 receptor: A novel therapy to prevent heart failure progression GPCR Binders, Drugs, and more Advances in GPCR-targeted drug development in dermatology Advances in small-molecule insulin secretagogues for diabetes treatment GPCRs in Neuroscience Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling GPCRs in Oncology and Immunology Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation Signaling by Neutrophil G Protein-Coupled Receptors that Regulate the Release of Superoxide Anions GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression Methods & Updates in GPCR Research Design, Synthesis, and Characterization of New δ Opioid Receptor-Selective Fluorescent Probes and Applications in Single-Molecule Microscopy of Wild-Type Receptors Structural and Molecular Insights into GPCR Function Vibrational Energy Landscapes and Energy Flow in GPCRs Allosterism in the adenosine A2A and cannabinoid CB2 heteromer Mechanistic insights from the atomic-level quaternary structure of short-lived GPCR oligomers in live cells Industry News Confo Therapeutics Announces EUR 60M Series B Financing to Advance a Pipeline of Novel GPCR-Modulating Therapies into Clinical Development How To Discover Biologics For Challenging Targets Drug discovery, a biophysics perspective Bio-Rad Adds Rapid Bispecific Antibody Prototyping and Screening Services to Pioneer Antibody Discovery Platform GPCR Events, Meetings, and Webinars November 5 - 7, 2024 | 16th Annual PEGS Europe   September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs NEW Postdoctoral Position NEW Postdoctoral research position Senior or Lead Researcher   Senior Scientist, Cryo-Electron Microscopy   Postdoctoral Research Associate Senior Scientist - Discovery Biotherapeutics    Join Dr. GPCR Ecosystem

📰 GPCR Weekly News, July 15 to 21, 2024 Hey everyone! Drum rolls, we’ve got 15 GPCR research papers, updates, industry news events, and GPCR ads curated just for you!   This week's highlight includes congrats to Omolade Otun , Chris de Graaf , Cherine Bechara , et al. for their work on Conformational dynamics underlying atypical chemokine receptor 3 activation   Michael Trogdon , J Silvio Gutkind , Edward C Stites , et al., for their study on   Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation Chiara D Mancinelli , Joshua Levitz , David Eliezer , et al. for their research on Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains Dr. GPCR University Exciting news! We are pleased to announce the scheduled dates for our highly anticipated courses led by Dr. Terry Kenakin . As of July 31st, early-bird registration for our premium Ecosystem members will begin, allowing you to benefit from this exclusive discount. Be sure to mark your calendars and secure your spot for this extraordinary learning opportunity! Course Schedule and Details Every Thursday at 10 am EST Principles of Pharmacology in Drug Discovery I -   Techniques for Effective Lead Optimization of Candidate Molecules Dates:  September 5th to 26th, 2024 Registrants will learn: Essentials of measuring pharmacologic activity of ligands (affinity, efficacy, co-operativity). Application of this knowledge to determine the mechanism of action of new GPCR ligands. The required elements of a comprehensive and effective GPCR Discovery. 2. Principles of Pharmacology in Drug Discovery II -   Advanced Methods for the Optimization of Candidate Selection Dates:  October 3rd to 31st, 2024 Registrants will learn: The powerful applications of new cellular assays to determine GPCR ligand behavior in different functional systems. Understanding real-time kinetics to predict activity and in vivo target coverage. New ligands and new GPCR behaviors that produce unique drug profiles (i.e., intracellular ligands and signaling, location bias, signaling bias). GPCR Event Highlight Get ready for the  11th Adhesion GPCR Workshop! Hosted by the Adhesion GPCR Consortium, this exciting event will occur in lively and culturally rich Mexico City from October 23 to 25, 2024 . It is an opportunity to connect with like-minded scientists and researchers and gain valuable insights into the latest developments in adhesion GPCR biology. Take advantage of the chance to showcase your creativity by participating in the Logo Contest . Submit your design by August 15, 2024, and stand a chance to have your creation represent this prestigious event. Are you interested in becoming a sponsor? Take advantage of the sponsorship opportunities and elevate your brand's presence at this crucial scientific gathering. Feel free to reach out to us at Hello@DrGPCR.com .  Let’s dive into the   Classified GPCR News  from July 15th to 21st, 2024 GPCR Activation and Signaling Conformational dynamics underlying atypical chemokine receptor 3 activation RhoA-mediated G12-G13 signaling maintains muscle stem cell quiescence and prevents stem cell loss Activation of Polycystin-1 Signaling by Binding of Stalk-derived Peptide Agonists GPCR Binders, Drugs, and more In silico exploration of 4(α-l-rhamnosyloxy)-benzyl isothiocyanate: A promising phytochemical-based drug discovery approach for combating multi-drug resistant Staphylococcus aureus Isolation, Structure Elucidation, and Biological Activity of the Selective TACR2 Antagonist Tumonolide and its Aldehyde from a Marine Cyanobacterium Fluorophore-Labeled Pyrrolones Targeting the Intracellular Allosteric Binding Site of the Chemokine Receptor CCR1 GPCRs in Cardiology, Endocrinology, and Taste GPCR-mediated regulation of beige adipocyte formation: Implications for obesity and metabolic health GPCRs in Neuroscience Chronic modulation of cAMP signaling elicits synaptic scaling irrespective of activity Neuronal GPCR NMUR-1 regulates energy homeostasis in response to pathogen infection GPCRs in Oncology and Immunology Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation Methods & Updates in GPCR Research A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models Reviews, GPCRs, and more Lessons from the physiological role of guanosine in neurodegeneration and cancer: Toward a multimodal mechanism of action? Structural and Molecular Insights into GPCR Function Entropy drives the ligand recognition in G-protein-coupled receptor subtypes Structural insights into ligand recognition, selectivity, and activation of bombesin receptor subtype-3 Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains Industry News Novartis continues to deliver strong sales growth and core margin expansion in Q2; raises FY 2024 bottom-line guidance  Crinetics Pharmaceuticals to Report Second Quarter 2024 Financial Results on August 8, 2024 Dynamic nature of G-protein coupled receptors Septerna Secures $150 Million in Series B Financing to Advance Pipeline of Novel GPCR-targeted Medicines GPCR Events, Meetings, and Webinars NEW November 5 - 7, 2024 | 16th Annual PEGS Europe   September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs NEW   Senior or Lead Researcher   NEW Senior Scientist, Cryo-Electron Microscopy   Postdoctoral Research Associate Senior Scientist - Discovery Biotherapeutics Post-Doctoral Fellow/Trainee Scientist; Biochemistry, Cellular and Mechanistic Pharmacology; Lead Discovery and Optimization   Join the Dr. GPCR Ecosystem

📰 GPCR Weekly News, July 8 to 14, 2024 Hello readers! Check out our GPCR coverage for this week. We have 15 GPCR papers, three industry news, and two job ads.   This week's highlight includes congrats to: Remi Janicot , and Dr. Mikel Garcia-Marcos for their work on Get ready to sharpen your tools:A short guide to heterotrimeric G protein activity biosensors Marta Lopez-Balastegui , Antonella Di Pizio , Jiafei Mao , Jana Selent , et al. for their research on the Relevance of GPCR dynamics for receptor activation, signalling bias and allosteric modulation Drs. Badr Sokrat , Michel Bouvier , et al. for their study on the Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes Dr. GPCR University We are excited to announce the dates for our upcoming courses led by Dr. Terry Kenakin . Early-bird registration for premium Ecosystem members opens on July 31st , so mark your calendars and take advantage of the discount! Course Schedule and Details Every Thursday at 10 am EST Principles of Pharmacology in Drug Discovery I -   Techniques for Effective Lead Optimization of Candidate Molecules Dates:  September 5th to 26th, 2024 Overview: This course delves into the essential pharmacologic techniques and knowledge necessary to create a GPCR Target Program aimed at discovering new drugs. GPCRs remain one of the most prolific and fertile therapeutic drug targets. Principles of Pharmacology in Drug Discovery II -   Advanced Methods for the Optimization of Candidate Selection Dates:  October 3rd to 31st, 2024 Overview: Building on the basics covered in Course I, this course explores advanced methods in GPCR utilization for drug therapy. Topics include the complex pleiotropic behaviors of GPCRs and how these can be harnessed for innovative drug discovery. GPCR Event Highlight 11th Adhesion GPCR Workshop Hosted by the Adhesion GPCR Consortium, this event will be held in vibrant Mexico City from October 23 to 25, 2024. Join fellow scientists and researchers in person to stay updated with adhesion GPCR biology. Important Deadlines: Abstract Submission : July 22, 2024. Submit your abstract today; the deadline is fast approaching! Logo Contest : Unleash your creativity and submit your design by August 15, 2024. Sponsorship Opportunities : Explore options for sponsoring this prestigious event. For more information, contact us at Hello@DrGPCR.com . Let’s dive into the   Classified GPCR News  from July 8th to 14th, 2024 GPCR Activation and Signaling GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and independent desensitization mechanisms Get ready to sharpen your tools:A short guide to heterotrimeric G protein activity biosensors Descriptive molecular pharmacology of the δ opioid receptor (DOR): A computational study with structural approach Mechanisms controlling haemolymph circulation under resting conditions in the chagas disease vector Rhodnius Prolixus (Stål ) Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes GPCRs in Neuroscience An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake The tick Ixodes scapularis has five different GPCRs specifically activated by ACP (adipokinetic hormone/corazonin-related peptide) GPCRs in Oncology and Immunology S1P Signaling Genes as Prominent Drivers of BCR-ABL1-Independent Imatinib Resistance and Six Herbal Compounds as Potential Drugs for Chronic Myeloid Leukemia Methods & Updates in GPCR Research High-throughput G protein-coupled receptor-based autocrine screening for secondary metabolite production in yeast Reviews, GPCRs, and more Class B1 GPCRs: Insights into Multi-Receptor Pharmacology for the Treatment of Metabolic Disease Relevance of G protein-coupled receptor (GPCR) dynamics for receptor activation, signalling bias and allosteric modulation Structural and Molecular Insights into GPCR Function Structural Mass Spectrometry Captures Residue-Resolved Comprehensive Conformational Rearrangements of a G Protein-Coupled Receptor Influence of the Water Model on the Structure and Interactions of the GPR40 Protein with the Lipid Membrane and the Solvent: Rigid versus Flexible Water Models Probing the energy landscape of the lipid interactions of the serotonin1A receptor Industry News Neurocrine Biosciences Announces Conference Call and Webcast of Second Quarter 2024 Financial Results G-Protein Coupled Receptors Global Market 2024 To Reach $4.09 Billion By 2028 At Rate Of 6.5% Trevena Announces $2M Non-Dilutive Financing Tranche and Reduction in Outstanding Liabilities in Connection with Existing ex-US Royalty Financing EuroscreenFast and GW Vitek Announce Strategic Distribution Partnership in Korea   GPCR Events, Meetings, and Webinars September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs NEW   Postdoctoral Research Associate   Senior Scientist - Discovery Biotherapeutics Post-Doctoral Fellow/Trainee Scientist; Biochemistry, Cellular and Mechanistic Pharmacology; Lead Discovery and Optimization   Director/Sr. Director GPCR Drug Discovery Biologist   Post-Doctoral Scientist- Molecular Pharmacology (FDE) Join Dr. GPCR Ecosystem

Hello everyone!  Check out our latest collection of 25 cutting-edge research papers on GPCRs and exciting updates on industry news related to GPCRs!   This week's highlight includes congrats to Edda Matthees , Drs.  Evi Kostenis , Carsten Hoffmann , et al., for their work on GRK specificity and Gβγ dependency determines the potential of a GPCR for arrestin-biased agonism Dr. Gunnar Schulte  for his study on the International Union of Basic and Clinical Pharmacology. CXV: The Class F of G Protein-Coupled Receptors Yusman Manchanda , Dr. Alejandra Tomas , et al. for their research on Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling Mónica Navarro-Sánchez , Drs. Ross Bathgate , Francisco Olucha-Bordonau , et al.    for their investigation on Modulation of contextual fear acquisition and extinction by acute and chronic relaxin-3 receptor (RXFP3) activation in the rat retrosplenial cortex Sarah Bernhard , Drs. Jianming Han , Tao Che  for their analysis of GPCR-G protein selectivity revealed by structural pharmacology Yao Lu , Drs Christopher Langmead ,  Gregory Stewart , et al. for their study on Molecular insights into orphan G protein-coupled receptors relevant to schizophrenia Dr. GPCR University The wait is finally over! We're thrilled to announce the dates for our upcoming courses led by the renowned Dr. Terry Kenakin . Mark your calendars because registration opens on July 18, 2024! These engaging online courses will take place every Thursday at 10 am EST. Here’s a sneak peek at what you can expect: Principles of Pharmacology in Drug Discovery I - Techniques for Effective Lead Optimization of Candidate Molecules Dates:  September 5th to 26th, 2024 Overview: GPCRs have been and arguably still are the most prolific and fertile therapeutic drug targets; this course describes the essential pharmacologic techniques and knowledge required to create a GPCR Target Program to discover new Drugs. Principles of Pharmacology in Drug Discovery II - Advanced Methods for the Optimization of Candidate Selection Dates:  October 3rd to 31st, 2024 Overview: This course continues with the basics learned in Course 1 and extends the ideas to apply GPCR utilization in drug therapy . Specifically, the ideas discussed cover the complex pleiotropic behaviors of GPCRs and how these may be exploited for new drug discovery. GPCR Event Highlight Immerse yourself in the cutting-edge world of adhesion GPCR research at the highly anticipated 11th Adhesion GPCR Workshop , hosted by the Adhesion GPCR Consortium. Taking place in the vibrant setting of Mexico City, this face-to-face gathering scheduled for October 23 to 25, 2024 , is poised to be a crucial meeting for scientists and researchers dedicated to the study of adhesion GPCR biology. Important Deadlines: Abstract Submission :  July 22, 2024. Submit your abstract today; you have less than two weeks! Logo Contest :   Unleash your creativity and submit your design by August 15th, 2024 Sponsorship Opportunities :  Explore sponsorship options for this prestigious event. For more information, contact us at Hello@DrGPCR.com .   Let’s dive into the   Classified GPCR News  from July 1 to 7, 2024 GPCR Activation and Signaling GPCR-MAPK signaling pathways underpin fitness trade-offs in whitefly G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets GRK specificity and Gβγ dependency determines the potential of a GPCR for arrestin-biased agonism The roles of RGS proteins in cardiometabolic disease GPCR Binders, Drugs, and more Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling Therapeutic potential of allosteric modulators for the treatment of gastrointestinal motility disorders GPCRs in Cardiology, Endocrinology, and Taste Geosmin, a Food- and Water-Deteriorating Sesquiterpenoid and Ambivalent Semiochemical, Activates Evolutionary Conserved Receptor OR11A1 Tongue-on-a-Chip: Parallel Recording of Sweet and Bitter Receptor Responses to Sequential Injections of Pure and Mixed Sweeteners GPCRs involved in metabolic diseases: pharmacotherapeutic development updates Targeting G protein-coupled receptors for heart failure treatment RAMP and MRAP accessory proteins have selective effects on expression and signalling of the CB1, CB2, GPR18 and GPR55 cannabinoid receptors GPCRs in Neuroscience Neuron specific quantitation of Gαolf expression and signaling in murine brain tissue Modulation of contextual fear acquisition and extinction by acute and chronic relaxin-3 receptor (RXFP3) activation in the rat retrosplenial cortex Unveiling the therapeutic prospects of EGFR inhibition in rotenone-mediated parkinsonism in rats: Modulation of dopamine D3 receptor Molecular insights into orphan G protein-coupled receptors relevant to schizophrenia Single nucleotide variations encoding missense mutations in G protein-coupled receptors may contribute to autism GPCRs in Oncology and Immunology Emerging GPCR targets for AUD: Insights from preclinical studies CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus Methods & Updates in GPCR Research Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic β-cells and neurons The application of artificial intelligence to accelerate G protein-coupled receptor drug discovery The application of targeted protein degradation technologies to G protein-coupled receptors Unravelling G protein-coupled receptor signalling networks using global phosphoproteomics Reviews, GPCRs, and more International Union of Basic and Clinical Pharmacology. CXV: The Class F of G Protein-Coupled Receptors Structural and Molecular Insights into GPCR Function Cryo-EM advances in GPCR structure determination GPCR-G protein selectivity revealed by structural pharmacology Industry News Neurocrine Biosciences Announces U.S. FDA Accepts New Drug Applications and Grants Priority Review for Crinecerfont for Pediatric and Adult Patients with CAH   adMare BioInnovations Expands with New Wet Laboratory Space in Vancouver   ThirtyFiveBio receives grant to continue work on GPR35 blockers   GPCR Events, Meetings, and Webinars September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs HIGHLIGHT   Principal Scientist, In vitro pharmacology   NEW Senior Scientist - Discovery Biotherapeutics NEW Post-Doctoral Fellow/Trainee Scientist; Biochemistry, Cellular and Mechanistic Pharmacology; Lead Discovery and Optimization   Director/Sr. Director GPCR Drug Discovery Biologist   Post-Doctoral Scientist- Molecular Pharmacology (FDE) Research Assistant     Join Dr. GPCR Ecosystem

Hello everyone! We have gathered 24 new research papers on GPCRs and updates on industry news related to GPCRs.   This week's highlight includes congrats to: Drs. Bryan Roth and Brian Krumm   for their study on Molecular glues as potential GPCR therapeutics Drs. András Tóth , László Hunyady , et al. for their work on G protein-coupled receptor endocytosis generates spatiotemporal bias in β-arrestin signaling Drs.   Kawthar Belkacemi , Philippe Rondard , Jean-Philippe Pin , and Laurent Prézeau ,   for their research on Heterodimers revolutionize the field of metabotropic glutamate receptors Kara Anazia , Dr. Matthew Eddy , et al. for their investigation on Interaction Networks within Disease-Associated GαS Variants Characterized by an Integrative Biophysical Approach   Dr. GPCR University We're thrilled to announce that Dr. Terry Kenakin  will lead two brand-new, back-to-back courses tailored for the Dr. GPCR Ecosystem this fall. Mark your calendars for September and October 2024, and stay tuned for registration details coming this month. These online courses will be held on Thursdays at 10 am EST. Save the dates: Course 1: Strategies for Successful Lead Optimization of Candidate Molecules Dates:  September 5th to 26th, 2024 Course 2: Advanced Methods for the Optimization of Candidate Selection Dates:  October 3rd to 31st, 2024 GPCR Event Highlight Join us for an in-person event with the Adhesion GPCR Consortium: the 11th Adhesion GPCR Workshop, which will be held in vibrant Mexico City from October 23 to 25, 2024. This key event will delve into adhesion GPCR Biology. Important Deadlines: Abstract Submission :  July 22, 2024. Submit your abstract today! Logo Contest :   Unleash your creativity and submit your design by August 15th, 2024 Sponsorship Opportunities :  Explore sponsorship options for this prestigious event. For more information, contact us at Hello@DrGPCR.com .   Let’s dive into the   Classified GPCR News  from June 24th to 30th, 2024 Adhesion GPCRs Novel Isoforms of Adhesion G Protein-Coupled Receptor B1 (ADGRB1/BAI1) Generated from an Alternative Promoter in Intron 17 The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects GPR56: A potential therapeutic target for neurological and psychiatric disorders GPCR Activation and Signaling Molecular basis for the activation of PAF receptor by PAF Heterodimers revolutionize the field of metabotropic glutamate receptors Molecular Basis of MC1R Activation: Mutation-Induced Alterations in Structural Dynamics Structural insights into ligand recognition and activation of the succinate receptor SUCNR1 G protein-coupled receptor endocytosis generates spatiotemporal bias in β-arrestin signaling Interaction Networks within Disease-Associated GαS Variants Characterized by an Integrative Biophysical Approach Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes Cellular lipids regulate the conformational ensembles of the disordered intracellular loop 3 in β2-adrenergic receptor Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR GPCR Binders, Drugs, and more Molecular glues as potential GPCR therapeutics A high-affinity, cis-on photoswitchable beta blocker to optically control β2-adrenergic receptors in vitro and in vivo GPCRs in Neuroscience Elucidating the activation mechanism of the proton-sensing GPR68 receptor Astrocytic GPCR signaling in the anterior cingulate cortex modulates decision making in rats Translation-independent association of mRNAs encoding protomers of the 5-HT 2A -mGlu2 receptor complex in living cells GPCRs in Oncology and Immunology Metabolic crosstalk: Extracellular ATP and the tumor microenvironment in cancer progression and therapy Agonists of galanin subtype 2 receptor may prevent pancreatic cancer and agonists of angiotensin II type 2 receptor may prevent colorectal cancer Distinct Activation Mechanisms of CXCR4 and ACKR3 Revealed by Single-Molecule Analysis of their Conformational Landscapes Methods & Updates in GPCR Research Protocol to visualize and quantify the COPII concentration and anterograde transport of nascent G protein-coupled receptors Effects of an external static EF on the conformational transition of 5-HT1A receptor: A molecular dynamics simulation study Monitoring norepinephrine release in vivo using next-generation GRABNE sensors Structural and Molecular Insights into GPCR Function Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor Industry News Nxera Pharma Receives US$10 Million from AbbVie as Collaboration Targeting Neurological Diseases Achieves First R&D Milestone Tectonic bets on GPCR heart failure drug following reverse merger with Avrobio Lilly signs $140M upfront partnership with Radionetics in latest radiopharma play   GPCR Events, Meetings, and Webinars September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs NEW Scientist; Biochemistry, Cellular and Mechanistic Pharmacology; Lead Discovery and Optimization   NEW Director/Sr. Director GPCR Drug Discovery Biologist   HIGHLIGHT   Principal Scientist, In vitro pharmacology   Post-Doctoral Scientist- Molecular Pharmacology (FDE) Research Assistant   Senior Scientist - Receptor Pharmacology Postdoctoral Scientist Join Dr. GPCR Ecosystem

Greetings to all! This Thursday, explore the latest content on GPCRs, which includes 29 informative research papers and industry news. Stay informed about the most recent developments in GPCR research and industry updates. This week's highlight includes congrats to: Ya-Tzu Li for her contributor article titled Do You Believe AI Could Accelerate Drug Discovery? Shane Wright, Michel Bouvier, et al., for their work on Conformation- and activation-based BRET sensors differentially report on GPCR-G protein coupling Samuel Liu, Preston Anderson, Sudarshan Rajagopal, Robert Lefkowitz, Howard Rockman for their review G Protein-Coupled Receptors: A Century of Research and Discovery Dr. GPCR University We are excited to announce that Dr. Terry Kenakin will conduct two back-to-back courses this fall. Save the September and October 2024 dates, and look for registration details in July. The two back-to-back courses are new and specially tailored to the Dr. GPCR Ecosystem and our community. The classes will be online Thursdays from 10 am EST. Save the dates from September 5th to 26th, 2024, to learn about Strategies for Successful Lead Optimization of Candidate Molecules. Save the dates from October 3rd to 31st, 2024, to learn more about the Advanced Methods for the Optimization of Candidate Selection. GPCR Event Highlight Join us for a special in-person event in collaboration with the Adhesion GPCR Consortium: The 11th Adhesion GPCR Workshop. This exciting event will occur in lively Mexico City from October 23 to 25, 2024, and will be a cornerstone for discussions in adhesion GPCR Biology. NEW DEADLINE July 22, 2024: Submit your abstract today! Logo Contest: Unleash your creativity by designing the event logo! Submit your entries by August 15th, 2024. Sponsorship Opportunities: Explore sponsorship possibilities for this prestigious event. For more details, contact us at Hello@DrGPCR.com. Let’s dive into the Classified GPCR News from June 17th to 23rd, 2024. GPCR Activation and Signaling GPCR-dependent and -independent arrestin signaling Direct GPCR-EGFR interaction enables synergistic membrane-to-nucleus information transfer TMC6 functions as a GPCR-like receptor to sense noxious heat via Gαq signaling Exploring the Activation Mechanism of the GPR183 Receptor GPCR Binders, Drugs, and more Target-based discovery of antagonists of the tick (Rhipicephalus microplus) kinin receptor identifies small molecules that inhibit midgut contractions Ligand-based analysis of the antifungal potential of phytosterols and triterpenes isolated from Cryptostegia grandiflora against Candida auris FKBP12 Development and therapeutic perspectives of CXCR4 antagonists for disease therapy GPCRs in Cardiology, Endocrinology, and Taste Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions GPCRs in Neuroscience Male-specific behavioral and transcriptomic changes in aging C. elegans neurons Activation of Gs Signaling in Cortical Astrocytes Does Not Influence Formation of a Persistent Contextual Memory Engram β-arrestins are scaffolding proteins required for Shh-mediated axon guidance GPCRs in Oncology and Immunology Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling Metallo-protease Peptidase M84 from Bacillusaltitudinis induces ROS-dependent apoptosis in ovarian cancer cells by targeting PAR-1 G protein-coupled receptors related to autoimmunity in postural orthostatic tachycardia syndrome The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer Identification of a G-protein coupled receptor-related gene signature through bioinformatics analysis to construct a risk model for ovarian cancer prognosis GprC of the nematode-trapping fungus Arthrobotrys flagrans activates mitochondria and reprograms fungal cells for nematode hunting Role and recent progress of P2Y12 receptor in cancer development Mutation Patterns Predict Drug Sensitivity in Acute Myeloid Leukemia Methods & Updates in GPCR Research The ufmylation cascade controls COPII recruitment, anterograde transport, and sorting of nascent GPCRs at ER Optical Control of TRPV1 Channels In Vitro with Tethered Photopharmacology Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology Optical Control of Cell-Surface and Endomembrane-Exclusive β-Adrenergic Receptor Signaling Conformation- and activation-based BRET sensors differentially report on GPCR-G protein coupling Reviews, GPCRs, and more Proteome-wide analysis reveals G protein-coupled receptor-like proteins in rice (Oryza sativa) G Protein-Coupled Receptors: A Century of Research and Discovery Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision Structural and Molecular Insights into GPCR Function Structure and dynamics of the pyroglutamylated RF-amide peptide QRFP receptor GPR103 Industry News EY Announces Scott Struthers, Ph.D., CEO and Founder of Crinetics Pharmaceuticals, as an Entrepreneur Of The Year® 2024 Pacific Southwest Award Winner Monlunabant by Inversago Pharma for Metabolic Syndrome: Likelihood of Approval Tectonic bets on GPCR heart failure drug following reverse merger with Avrobio Addex Pharma unveils new mGlu7 receptor negative allosteric modulators Trevena Announces Preclinical TRV045 Data Providing Insight Into Novel Mechanism of Analgesic Effect in Chronic Neuropathic Pain Model and Demonstrating Statistically Significant Anti-Seizure Activity in Epilepsy Models Biophysicists decipher functionality of adrenaline-binding receptor Tectonic plates more than $130m in new funding and goes public GPCR Events, Meetings, and Webinars NEW June 27, 2024 | FREE GPCR Forum ECI Zoominar June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 NEW September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024 October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs HIGHLIGHT Principal Scientist, In vitro pharmacology NEW Post-Doctoral Scientist- Molecular Pharmacology (FDE) NEW Research Assistant Senior Scientist - Receptor Pharmacology Postdoctoral Scientist Senior Research Associate/Associate Scientist, Protein Science Post-Doctoral Fellow—Pharmacology/Cell Biology/Biochemistry Join Dr. GPCR Ecosystem