G protein-coupled receptors (GPCRs) are integral membrane proteins crucial for sensing extracellular signals, including hormones, neurotransmitters, and environmental cues. These receptors initiate intracellular signaling cascades upon activation, ultimately regulating a myriad of physiological processes. Central to GPCR function are G proteins, comprising subfamilies such as Gs, Gi/o, Gq/11, and G12/13, which orchestrate downstream signaling events, including the modulation of cyclic adenosine monophosphate (cAMP), calcium mobilization, and extracellular signal-regulated kinase (ERK) activation [1]. Traditionally, second messenger assays measuring cAMP accumulation, calcium mobilization, and ERK phosphorylation have been pivotal in deciphering GPCR activity, particularly in drug discovery endeavors [2]. However, these conventional assays often provide limited information on intermediate signaling events due to pathway crosstalk and signal amplification [3]. Also, most second messenger assays are primarily endpoint measurements and do not allow practical measurement of the kinetics of signaling. The emergence of resonance energy transfer (RET) techniques, notably Fluorescence Resonance Energy Transfer (FRET) and Bioluminescence Resonance Energy Transfer (BRET), has revolutionized the study of GPCRs by enabling real-time monitoring of protein-protein interactions and intracellular signaling dynamics[4]. FRET and BRET sensors operate on the principle of energy transfer between a fluorescent or luminescent donor and acceptor molecules within close proximity, typically within 100Å. These biosensors have facilitated the investigation of various aspects of GPCR signaling, including ligand binding (e.g NanoBRET ligand binding [5]), effector protein recruitment assays (e.g G protein recruitment assay [6], mini-G recruitment assay [7], GRK and β-arrestin recruitment assays [8]), G protein activation (e.g TRUPATH assay [9]), receptor trafficking ( e.g FYVE assay [10]),  β-arrestin dynamics ( e.g FLAsH biosensor [11]), cAMP production (e.g CAMYEL assay [12]) , and ERK activity (e.g YEN assay [13]), among others. One of the significant advantages of FRET and BRET-based sensors is their ability to provide real-time readouts of pharmacological activity, allowing for the determination of drug kinetics—a critical aspect in drug development [14]. Moreover, these experiments can be conducted in live cells, preserving the physiological context and minimizing artifacts associated with sample preparation for endpoint measurements. Despite their immense potential, utilizing FRET and BRET sensors in GPCR research comes with challenges, including expensive cost of reagents, optimizing sensor expression levels and adapting these systems to disease-relevant models. Addressing these hurdles is essential for translating findings from cellular models to clinically relevant scenarios. Some innovative solutions have been the development of the BERKY and the ONE-GO biosensors, designed to facilitate their application in disease models[3, 15]. BERKY consists of a membrane linker, a BRET donor, an ER/K α-helix linker, a BRET acceptor, and an active G protein detector. The ONE-GO biosensors, designed in a single vector, incorporate a G protein tagged with a YFP acceptor and a G protein detector tagged with an Nluc donor. Both BERKY and ONE-GO biosensors are engineered to detect the GTP-bound Gα subunit, serving as a proxy for G protein activation and have been optimized for use in detecting GPCR activity in primary cells. In conclusion, FRET and BRET-based sensors have transformed the landscape of GPCR research, offering unprecedented insights into the intricacies of GPCR signaling. These techniques not only enhance our understanding of fundamental cellular processes, but also hold immense promise in accelerating drug discovery efforts by enabling the precise characterization of pharmacological interventions in real time. As technology continues to advance, leveraging RET-based sensors will undoubtedly continue to propel our quest to unravel the complexities of GPCR signaling and pave the way for novel therapeutic strategies. 1.      Gilman, A.G., G proteins: transducers of receptor-generated signals. Annu Rev Biochem, 1987. 56: p. 615-49. 2.      Zhou, Y., et al., Multiple GPCR Functional Assays Based on Resonance Energy Transfer Sensors. Front Cell Dev Biol, 2021. 9: p. 611443. 3.      Maziarz, M., et al., Revealing the Activity of Trimeric G-proteins in Live Cells with a Versatile Biosensor Design. Cell, 2020. 182(3): p. 770-785.e16. 4.      Salahpour, A., et al., BRET biosensors to study GPCR biology, pharmacology, and signal transduction. Frontiers in Endocrinology, 2012. 3. 5.      Zhao, P., et al., Activation of the GLP-1 receptor by a non-peptidic agonist. Nature, 2020. 577(7790): p. 432-436. 6.      Galés, C., et al., Real-time monitoring of receptor and G-protein interactions in living cells. Nat Methods, 2005. 2(3): p. 177-84. 7.      Wan, Q., et al., Mini G protein probes for active G protein-coupled receptors (GPCRs) in live cells. J Biol Chem, 2018. 293(19): p. 7466-7473. 8.      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. 9.      Olsen, R.H.J., et al., TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome. Nat Chem Biol, 2020. 16(8): p. 841-849. 10.    Namkung, Y., et al., Monitoring G protein-coupled receptor and β-arrestin trafficking in live cells using enhanced bystander BRET. Nature Communications, 2016. 7(1): p. 12178. 11.    Strungs, E.G., L.M. Luttrell, and M.H. Lee, Probing Arrestin Function Using Intramolecular FlAsH-BRET Biosensors. Methods Mol Biol, 2019. 1957: p. 309-322. 12.    Jiang, L.I., et al., Use of a cAMP BRET sensor to characterize a novel regulation of cAMP by the sphingosine 1-phosphate/G13 pathway. J Biol Chem, 2007. 282(14): p. 10576-84. 13.    Goyet, E., et al., Fast and high resolution single-cell BRET imaging. Sci Rep, 2016. 6: p. 28231. 14.    Pfleger, K.D., R.M. Seeber, and K.A. Eidne, Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nat Protoc, 2006. 1(1): p. 337-45. 15.    Janicot, R., et al., Direct interrogation of context-dependent GPCR activity with a universal biosensor platform. bioRxiv, 2024.

Hello readers! We got a little busy with all the major events at Dr.GPCR, so our weekly news looks slightly different. We will be back next week with our regular weekly GPCR news digest. In the meantime, you can always check the  Classified GPCR News from the last weeks. Today, we celebrate a huge milestone by releasing Episode #150 of the Dr. GPCR Podcast. Join us in this wonderful episode to meet the team of volunteers behind the work you see. The story behind how Dr.GPCR came to be, the people behind the process, the great anecdotes, and what’s coming next. We also have some important announcements in today’s episode, so join us in this celebration and be the first to know about all the changes coming to Dr. GPCR. Today is also the first session of our hands-on workshop with Dr. Sam Hoare. If you aren't joining us this time, stay tuned for more Dr. GPCR University content coming soon.

Hello readers! Check out our GPCR coverage for this week. We have 15 GPCR papers, two industry news, and one job ad. This week's highlight includes congrats to: André Nguyen Dietzsch, Simone Prömel, et al. for their work on the Dysfunction of the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity Norton Cheng, JoAnn Trejo, et al. for their research on Ubiquitin-driven GPCR Inflammatory Signaling at the Endosome Dr. GPCR University Hurry! Only five spots left! Team Registrations are also open!  You have until 5 pm EST tomorrow to register. We are pleased to announce five full scholarship opportunities for Dr. Hoare's workshop for individuals who live and work in developing countries. Please complete this form to take advantage of this opportunity on a first-come, first-served basis. We also ask that you share this with your colleagues. We define a developing country based on World Bank Classifications for its 2024 fiscal year. Join our upcoming Dr. GPCR University hands-on workshop with Dr. Samuel Hoare on Advanced data analysis for GPCR pharmacology, which will be held on Thursdays between May 9th and May 30th, 2024, from 10 am to 12 pm EDT. The workshop includes: Four x 2-hour Zoom sessions One-on-one meeting with Dr. Hoare Access to Dr. GPCR Ecosystem group Access to course materials and recordings Completion certificate One-year Dr. GPCR Ecosystem Premium Membership (restrictions apply) Early bird discount on future courses (restrictions apply) Dr. GPCR Symposia Join us on June 7th for our symposium on Structural and Molecular Insights into GPCR Function. Stay tuned for more details. Premium members get access to on-demand content from past events. Submit a few slides for a poster presentation to showcase your research and network with our community. Fill out this form to get started! Remember to give us your feedback by completing our survey if you've participated in our symposiums. Dr. GPCR Matchmaking Did you check out our first job opportunity spotlight for a Principal Scientist In Vitro Pharmacology? Our Chief Matchmaker, Mark Schmeizl, had a great conversation about this position with Beth Fleck, Director of In Vitro Pharmacology at Crinetics Pharmaceuticals! Don't miss out! Also, Mark Schmeizl can help you find your perfect match if you want to hire or be hired. Mark has experience connecting candidates with employers and will work with you to understand your needs and preferences to ensure a successful match. Contact Mark today to get started. Let’s dive into the Classified GPCR News from April 22nd to 28th, 2024 Adhesion GPCRs Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity GPCR Activation and Signaling Variable CGRP family peptide signaling durations and the structural determinants thereof Ubiquitin-driven G Protein-Coupled Receptor Inflammatory Signaling at the Endosome GPCR Binders, Drugs, and more Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor GPCRs in Cardiology, Endocrinology, and Taste Discovery of a SUCNR1 antagonist for potential treatment of diabetic nephropathy: In silico and in vitro studies GPCRs in Neuroscience Phytocannabinoids in neuromodulation: from omics to epigenetics The receptor tyrosine kinase IGF1R and its associated GPCRs are co-regulated by the noncoding RNA NEAT1 in Alzheimer's disease Parenting behaviors in mice: Olfactory mechanisms and features in models of autism spectrum disorders Systematic characterization of multi-omics landscape between gut microbial metabolites and GPCRome in Alzheimer's disease Methods & Updates in GPCR Research Single-chain fluorescent integrators for mapping G-protein-coupled receptor agonists Development of a synthetic relaxin-3/INSL5 chimeric peptide ligand for NanoBiT complementation binding assays Generation of a deep mouse brain spectral library for transmembrane proteome profiling in mental disease models Reviews, GPCRs, and more The nematode-trapping fungus Arthrobotrys oligospora detects prey pheromones via G protein-coupled receptors Structural and Molecular Insights into GPCR Function Fungal alkaloid malbrancheamide reorients the lipid binding domain of GRK5 Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs Industry News Introducing Big Sky BacMam Chemical tool illuminates pathways used by dopamine, opioids and other neuronal signals GPCR Events, Meetings, and Webinars May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 NEW July 8 - 10, 2024 | 4th IRN i-GPCRnet Annual 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 Post Doctoral Fellow Postdoc Position Principal Scientist, In vitro pharmacology Senior Associate Scientist - Global Research Technologies Novo Nordisk Scientist I - Global Research Technologies Novo Nordisk Postdoctoral Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Join Dr. GPCR Ecosystem

Hello there! We have some exciting updates for all the GPCR enthusiasts out there. This week, we have a comprehensive coverage of 12 GPCR research papers. Additionally, we have six industry news. And if you're looking for a new job opportunity, we have one job ad. This week's highlight includes congrats to: Luca Franchini and Cesare Orlandi for their research on Deorphanization of G Protein Coupled Receptors (GPCRs): a historical perspective Monserrat Avila-Zozaya article on From DNA day to GPCR genomics Dr. GPCR University Hurry! 17 out of the 25 spots have been filled! Team Registrations are also available!  You have until May 3rd, 2023 to register. We are pleased to announce five full scholarship opportunities for Dr. Hoare's workshop for individuals who live and work in developing countries. Please complete this form to take advantage of this opportunity on a first-come, first-served basis. We also ask that you share this with your colleagues. We define a developing country based on World Bank Classifications for its 2024 fiscal year. Join our upcoming Dr. GPCR University hands-on workshop with Dr. Samuel Hoare on Advanced data analysis for GPCR pharmacology, which will be held on Thursdays between May 9th and May 30th, 2024, from 10 am to 12 pm EDT. The workshop includes: Four x 2-hour Zoom sessions One-on-one meeting with Dr. Hoare Access to Dr. GPCR Ecosystem group Access to course materials and recordings Completion certificate One-year Dr. GPCR Ecosystem Premium Membership (restrictions apply) Early bird discount on future courses (restrictions apply) Check our conversation with Dr. Sam Hoare about this hands-on workshop HERE ⬇⬇⬇ Dr. GPCR Symposia Join us on June 7th for our symposium on Structural and Molecular Insights into GPCR Function. Stay tuned for more details. Premium members get access to on-demand content from past events. Submit a few slides for a poster presentation to showcase your research and network with our community. Fill out this form to get started! Don't forget to give us your feedback by completing our survey if you've participated in our symposiums. Dr. GPCR Matchmaking Did you check out our first job opportunity spotlight for a Principal Scientist In Vitro Pharmacology? Our Chief Matchmaker, Mark Schmeizl, had a great conversation about this position with Beth Fleck, Director of In Vitro Pharmacology at Crinetics Pharmaceuticals! Don't miss out! Also, if you are looking to hire or be hired, Mark Schmeizl can help you find your perfect match. Mark has experience connecting candidates with employers and will work with you to understand your needs and preferences to ensure a successful match. Contact Mark today to get started. Let’s dive into the Classified GPCR News from April 15th to 21st, 2024 GPCR Activation and Signaling Beneath the surface: endosomal GPCR signaling The M3 muscarinic acetylcholine receptor can signal through multiple G protein families Rapid elucidation of agonist-driven regulation of the neurokinin 1 receptor using a GPCR phosphorylation immunoassay GPCR Binders, Drugs, and more Identification of 1,3,8-triazaspiro[4.5]decane-2,4-dione Derivatives as a Novel Delta Opioid Receptor-Selective Agonist Chemotype GPCRs in Neuroscience Calcium-sensing receptor regulates Kv7 channels via Gi/o protein signalling and modulates excitability of human induced pluripotent stem cell-derived nociceptive-like neurons Characterization of myoinhibitory peptide signaling system and its implication in larval metamorphosis and spawning behavior in Pacific abalone The role of orphan G protein-coupled receptors in pain GPCRs in Oncology and Immunology Deciphering a GPCR-lncRNA-miRNA Nexus: Identification of an Aberrant Therapeutic Target in Ovarian Cancer Methods & Updates in GPCR Research Alared: Solvatochromic and Fluorogenic Red Amino Acid for Ratiometric Live-cell Imaging of Bioactive Peptides Cascaded amplifying circuit enables sensitive detection of fungal pathogens In Silico Analyses of Vertebrate G-Protein-Coupled Receptor Fusions United With or Without an Additional Transmembrane Sequence Indicate Classification into Three Groups of Linkers Reviews, GPCRs, and more Deorphanization of G Protein Coupled Receptors (GPCRs): a historical perspective Industry News Addex Therapeutics Reports Full Year 2023 Financial Results And Provides Corporate Update Aelis Farma announces the Last Patient, Last Visit in its clinical phase 2b trial with AEF0117 for the treatment of cannabis use disorder Orion Biotechnology will be presenting at the 19th Biopharma Drug Discovery Nexus Salipro Biotech will participate in BioKorea2024 Domain Therapeutics Appoints Sean A. MacDonald as Chief Executive Officer Nxera Pharma Announces Exclusive Supply and Distribution Agreement with Handok for PIVLAZ™ in South Korea Amgen To Present Tezspire® Phase 2A COPD Data At ATS 2024 GPCR Events, Meetings, and Webinars April 17 – May 1, 2024 | FREE ASPET Virtual Award Lecture Series May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Postdoc Position Principal Scientist, In vitro pharmacology Senior Associate Scientist - Global Research Technologies Novo Nordisk Scientist I - Global Research Technologies Novo Nordisk Postdoctoral Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Join Dr. GPCR Ecosystem

Hello Dr. GPCR ecosystem members!  As Chief Matchmaker, I recently had the pleasure of speaking with Beth Fleck, Director of In Vitro Pharmacology at Crinetics Pharmaceuticals.  Beth is also the hiring manager for their open Principal Scientist, In Vitro Pharmacology role posted in the Dr. GPCR ecosystem.  Our conversation provided additional insight you cannot find in a job description, so I thought I’d share this insight with you. Mark:  “Beth, why did you decide to join Crinetics?” Beth:  “I was invited to join Crinetics a few years ago by some former colleagues and their description of the company was very intriguing: a biology focused, small molecule focused, smaller drug discovery company with a great work environment.  Crinetics hires people with big brains and small egos.” Mark:  “Have you found this to be accurate?” Beth:  “Yes.  There are a lot of learning opportunities at Crinetics.  We collaborate and cross-pollenate a lot.” Mark:  “So, what are the qualities of the perfect candidate for the Principal Scientist role?” Beth:  “We are looking for a thinker and problem solver who is able to learn.  Someone with strong assay development skills as well as strong data analysis and interpretation skills.” Mark:  “Are there particular assay types of interest?” Beth:  “We focus on biochemical, cell based, and radioligand binding assays to enable SAR, MOA, lead optimization, and new target discovery.  Top candidates will have a solid foundation in GPCR pharmacology as well as some experience in drug discovery.” Mark:  “Beth, why would someone want you as their boss?” Beth:  “Well, I enjoy training and mentoring team members.  I keep an open door and you’ll find me among the team in the lab quite often.  There’s comradery and open exchange in our team and I strive to provide learning opportunities for career development.” So, if you are looking for an on-site opportunity in San Diego and Beth’s comments sound good to you, please reach out to me at mschmeizl@grnwindsor.com or 860-325-3505 and we can dig a bit deeper. By: Mark Schmeizl Chief Matchmaker at Dr. GPCR

Hello readers! Check out our GPCR coverage for this week. We have 15 GPCR papers, three industry news, one event, and one job ad. This week's highlight includes congrats to: Tessa de Vries, Graham Ladds, Antoinette MaassenVanDenBrink, et al. for their work on Intracellular pathways of calcitonin gene-related peptide-induced relaxation of human coronary arteries: A key role for Gβγ subunit instead of cAMP. Katharina Grotsch, Bryan L Roth, Valery V Fokin  et al. for their research on Virtual Screening of a Chemically Diverse "Superscaffold" Library Enables Ligand Discovery for a Key GPCR Target Gunnar Schulte, Lukas Grätz, Pawel Kozielewicz, et al. for their study on Frizzleds act as dynamic pharmacological entities Marina Casiraghi, Robert J Lefkowitz, Peter Gmeiner, Brian K Kobilka et al. for their investigation on Molecular insights into G protein coupling specificity at a class A GPCR Jianjun Cao, Arthur Christopoulos, Patrick M. Sexton et al. for their job on Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein Dr. GPCR University Hurry! 11 out of the 25 spots have been filled! Team Registrations are also available! Early bird registration ends TODAY. Join our upcoming Dr. GPCR University hands-on workshop with Dr. Samuel Hoare on Advanced data analysis for GPCR pharmacology, which will be held on Thursdays between May 9th and May 30th, 2024, from 10 am to 12 pm EDT. The workshop includes: Four x 2-hour Zoom sessions One-on-one meeting with Dr. Hoare Access to Dr. GPCR Ecosystem group Access to course materials and recordings Completion certificate One-year Dr. GPCR Ecosystem Premium Membership (restrictions apply) Early bird discount on future courses (restrictions apply) Save 25% with early bird registration that ends TODAY!! We are pleased to announce five full scholarship opportunities for Dr. Hoare's workshop for individuals who live and work in developing countries. Please complete this form to take advantage of this opportunity. It's on a first-come, first-served basis. We also ask that you share this with your eligible colleagues. We define a developing country based on World Bank Classifications for its 2024 fiscal year. Check our conversation with Dr. Sam Hoare about this hands-on workshop HERE ⬇⬇⬇ Dr. GPCR Symposia Join us on June 7th for our next symposium on Structural and Molecular Insights into GPCR Function. Stay updated for more details. Do you want to re-watch our recorded events? As a premium member, access on-demand content from past Dr. GPCR Symposiums and much more! If you have any research you would like to showcase to our community, you can submit a poster presentation. It doesn’t have to be a complete poster, just a few slides to spark the conversation. This is an excellent opportunity to network and increase your visibility on our platform. To begin, please fill out this form! If you've participated in our symposiums, please take a few minutes to complete this survey. Your feedback is valuable to us. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from April 8th to 14th, 2024 Adhesion GPCRs High incidence of imperforate vagina in ADGRA3-deficient mice GPCR Activation and Signaling Local anesthetics inhibit muscarinic acetylcholine receptor-mediated calcium responses and the recruitment of β-arrestin in HSY human parotid cells GPCR kinase subtype requirements for arrestin-2 and -3 translocation to the cannabinoid CB1 receptor and the consequences on G protein signalling Melanin-concentrating hormone receptor 1 is discarded by exosomes after internalization Intracellular pathways of calcitonin gene-related peptide-induced relaxation of human coronary arteries: A key role for Gβγ subunit instead of cAMP GPCR Binders, Drugs, and more Virtual Screening of a Chemically Diverse "Superscaffold" Library Enables Ligand Discovery for a Key GPCR Target GPCRs in Cardiology, Endocrinology, and Taste Orphan GPCR GPRC5C Facilitates Angiotensin II-Induced Smooth Muscle Contraction GPCRs in Neuroscience Evolutionary origins of bitter taste receptors in jawed vertebrates Methods & Updates in GPCR Research Exploring GPCR conformational dynamics using single-molecule fluorescence Droplet-based microfluidic platform for detecting agonistic peptides that are self-secreted by yeast expressing a G-protein-coupled receptor Reviews, GPCRs, and more The GLP-1R as a model for understanding and exploiting biased agonism in next-generation medicines G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery Frizzleds act as dynamic pharmacological entities Structural and Molecular Insights into GPCR Function Molecular insights into G protein coupling specificity at a class A GPCR Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein Industry News Monash University retains its N° 2 global ranking for Pharmacy and Pharmacology Addex Therapeutics to Release Full-Year 2023 Financial Results and Host Conference Call on April 18, 2024 Nxera Pharma Notes Successful Development Progress of Partnered Schizophrenia Candidate NBI-1117568 GPCR Events, Meetings, and Webinars NEW April 17 – May 1, 2024 | FREE ASPET Virtual Award Lecture Series May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Principal Scientist, In vitro pharmacology Senior Associate Scientist - Global Research Technologies Novo Nordisk Scientist I - Global Research Technologies Novo Nordisk Postdoctoral Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Join Dr. GPCR Ecosystem

April is the month of DNA Day, a special day commemorating the discovery of the DNA double helix structure in 1953 and the completion of the Human Genome Project in 2003. In the United States, DNA Day was officially celebrated on April 25th, 2003. Since then, the National Human Genome Research Institute (NHGRI) has supported annual events across the country to celebrate, learn and discuss the latest advances in genomic research. Eventually, April 25th was declared and recognized as International DNA Day1. What does DNA Day have to do with GPCRs? The discovery of DNA's double helical structure was a scientific milestone that revolutionized molecular biology. It provided a fundamental understanding of how genetic information is stored and transferred between generations. This breakthrough also paved the way for the development of genomics, a field of study that examines an organism's entire DNA or genome, including its genes, regulatory elements, and non-coding DNA sequences. Genomics, in turn, played a crucial role in the discovery and sequencing of the beta-adrenergic receptor (βAR), the first GPCR to be identified by Robert Lefkowitz and colleagues during their study of the effects of adrenaline on cells2. This intersection of genomics and GPCR research sparked a new era of a comprehensive understanding of GPCR biology, the development of GPCR-targeted drugs, and the exploration of GPCRs as key regulators of physiological processes and therapeutic targets in medicine. The completion of the Human Genome Project revealed that GPCR genes in the human genome range from approximately 800 to over 1,000. This variation is due to factors such as alternative splicing, gene duplications, and variability in genomic methods. However, it's worth noting that the total count of GPCR genes in the human genome is still being refined as genome sequencing technologies and bioinformatics tools improve. Also, ongoing research may discover new GPCRs or refine existing data, which could lead to adjustments in the total count of GPCR genes in the human genome. Additionally, genomic approaches such as transcriptomics and proteomics have provided insights into the expression patterns and post-translational modifications of GPCRs under different physiological conditions3. Another significant impact of genomics on GPCR research is the elucidation of receptor structure and function. Advances in structural genomics, coupled with techniques like X-ray crystallography and cryo-electron microscopy, have allowed us to understand the structural dynamics during receptor activation. Thanks to recent scientific advances, we now have a better understanding of the structural changes that happen when a receptor is activated. For example, we know that transmembrane helices move during receptor activation and that the DRY motif plays a vital role in activating G-proteins and binding to B-arrestin4. Additionally, there have been recent discoveries of the conformational changes that occur during G-protein activation by the β2-adrenergic receptor, using a time-resolved approach5. Furthermore, computational genomics approaches, such as structural bioinformatics analysis, have facilitated drug discovery and design targeting GPCRs, leading to the development of novel therapeutics. Advances in genomic technologies, such as genome-wide association studies and next-generation sequencing, have enabled the uncovering of associations between GPCR genetic variants and diseases. The genetic variation in GPCRs is extensive; databases like GPCRdb provide a large database of genetic variations (including single nucleotide polymorphisms or SNPs) that may impact the structure or function of GPCRs. For example over 160 SNPs have been reported for the β2AR gene, with some of these SNPs having clinical significance. Another example is the cannabinoid receptor 1 with a total of 248 SNPs, where 190 missense mutations were predicted to have a functional effect4. Overal, genomics has been a driving force in advancing scientific knowledge and innovation within the GPCR world. The integration of genomics with structural biology, pharmacology, bioinformatics, and clinical research has opened new avenues for exploring GPCR biology, developing targeted therapies, and translating genomic discoveries into clinical practice. As we celebrate Happy DNA Day, it's a testament to how genomics has revolutionized our understanding of GPCRs and their role in human health. References National Human Genome Research Institute, U. S. (2002) National Human Genome Research Institute. United States. https://www.genome.gov/ Dixon, R. A., Kobilka, B. K., Strader, D. J., Benovic, J. L., Dohlman, H. G., Frielle, T., Bolanowski, M. A., Bennett, C. D., Rands, E., Diehl, R. E., Mumford, R. A., Slater, E. E., Sigal, I. S., Caron, M. G., Lefkowitz, R. J., & Strader, C. D. (1986). Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature, 321(6065), 75–79. https://doi.org/10.1038/321075a0 Fredriksson, R., Lagerström, M. C., Lundin, L. G., & Schiöth, H. B. (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular pharmacology, 63(6), 1256–1272. https://doi.org/10.1124/mol.63.6.1256 Syed Haneef, S. A., & Ranganathan, S. (2019). Structural bioinformatics analysis of variants on GPCR function. Current opinion in structural biology, 55, 161–177. https://doi.org/10.1016/j.sbi.2019.04.007 Papasergi-Scott, M. M., Pérez-Hernández, G., Batebi, H., Gao, Y., Eskici, G., Seven, A. B., Panova, O., Hilger, D., Casiraghi, M., He, F., Maul, L., Gmeiner, P., Kobilka, B. K., Hildebrand, P. W., & Skiniotis, G. (2023). Time-resolved cryo-EM of G protein activation by a GPCR. bioRxiv : the preprint server for biology, 2023.03.20.533387. https://doi.org/10.1101/2023.03.20.533387

Greetings readers! We're excited to share our coverage of the latest developments in GPCRs for this week. In this edition, we have curated eight GPCR papers, five industry news, and two job ads. This week's highlight includes congrats to: David A Cooper, David Minh, et al., for their research on Intracellular pocket conformations, determine signaling through the μ opioid receptor. Dr. Minh and the team are looking for collaborators from academia and industry. Please reach out to him by email today! Dr. GPCR University Hurry! 3 out of the 25 spots have been filled! Team Registrations are also available! Early bird registration ends on April 18th. Join our upcoming Dr. GPCR University hands-on workshop with Dr. Samuel Hoare on Advanced data analysis for GPCR pharmacology, which will be held on Thursdays between May 9th and May 30th, 2024, from 10 am to 12 pm EDT. The workshop includes: Four x 2-hour Zoom sessions One-on-one meeting with Dr. Hoare Access to Dr. GPCR Ecosystem group Access to course materials and recordings Completion certificate One-year Dr. GPCR Ecosystem Premium Membership (restrictions apply) Early bird discount on future courses (restrictions apply) Save 25% with early bird registration until April 18th. We are pleased to announce five full scholarship opportunities for Dr. Hoare's workshop for individuals who live and work in developing countries. Please complete this form to take advantage of this opportunity. It's on a first-come, first-served basis. We also ask that you share this with your eligible colleagues. We define a developing country based on World Bank Classifications for its 2024 fiscal year. Dr. GPCR Symposia Join us on June 7th for our next symposium on Structural and Molecular Insights into GPCR Function. Stay updated for more details. Do you want to re-watch our recorded events? As a premium member, access on-demand content from past Dr. GPCR Symposiums and much more! If you have any research you would like to showcase to our community, you can submit a poster presentation. It doesn’t have to be a complete poster, just a few slides to spark the conversation. This is an excellent opportunity to network and increase your visibility on our platform. To begin, please fill out this form! If you've participated in our symposiums, please take a few minutes to complete this survey. Your feedback is valuable to us. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from April 1st to 7th, 2024 GPCR Activation and Signaling GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage Intracellular pocket conformations determine signaling through the μ opioid receptor GPCR Binders, Drugs, and more Predicting associations between drugs and G protein-coupled receptors using a multi-graph convolutional network GPCRs in Cardiology, Endocrinology, and Taste Dissecting a Brake for Airway Smooth Muscle Cell Movement Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease GPCRs in Oncology and Immunology Chemoattractant receptor signaling in humoral immunity Industry News Neurosterix launches with $63M to Advance Allosteric Modulator Therapeutics for Neurological Disorders Aelis Farma Reports Its 2023 Annual Financial Resultsand Confirms Its 2024 Outlook Sosei Heptares officially changed their name to Nxera Domain Therapeutics to participate at premier investor and healthcare conferences Montana Molecular is joining the BioTools Innovator program GPCR Events, Meetings, and Webinars May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Senior Associate Scientist - Global Research Technologies Novo Nordisk Scientist I - Global Research Technologies Novo Nordisk Postdoctoral Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Join Dr. GPCR Ecosystem

Hello readers! Check out our GPCR coverage for this week. We have 17 GPCR papers and eight industry news. This week's highlight includes congrats to: Junyi Liang, Niña Caculitan, and Adam W Smith for their research on β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells Dr. GPCR University Get ready for our next Dr. GPCR University hands-on workshop with Dr. Samuel Hoare on Advanced data analysis for GPCR pharmacology, which will be held on Thursdays between May 9th and May 30th, 2024, from 10 am to 12 pm EDT. The workshop includes: 4x 2 hours live Zoom sessions (45-50 minutes lecture + 1-hour Q&A) Thirty minutes one-on-one meetings with Dr. Hoare, according to his availability Access to the cohort’s Dr. GPCR Ecosystem group, where you can find Dr. Hoare and your classmates Access to the course materials and recordings once the course is completed Course completion certificate signed by Dr. Hoare and Dr. GPCR Complementary one-year Dr. GPCR Ecosystem Premium Membership ($250 value savings) - Only applicable to individual registrations Access to all content and all Dr. GPCR Ecosystem perks, including our forums, private groups, and all Ecosystem members Extended early bird discounts on future Dr.GPCR University courses in the next 12 months -  Only applicable to individual registrations This course will take a practical approach to Dr. Terry Kenakin’s Applying Pharmacology to Drug Discovery course. Continue to increase your knowledge of Pharmacology by joining this practical approach class today. Take advantage of the early bird registration until April 18th, 2024, to save 25%! Reserve your spot today. We are pleased to announce five full scholarship opportunities for Dr. Hoare's workshop for individuals who live and work in developing countries. Please complete this form to take advantage of this opportunity. We also ask that you share this with your eligible colleagues. Dr. GPCR Symposia With a premium membership, you can watch on-demand the Dr. GPCR Symposium on GPCR activation and signaling sessions. Our next symposium on Structural and Molecular Insights into GPCR Function is scheduled for June 7th. Stay tuned for more updates. If you want to showcase your research, you can submit a poster presentation to our community, take advantage of networking opportunities, and raise your profile on our platform. Get started by filling out this form! If you have a few minutes to spare and have participated in our symposiums, we would appreciate it if you could complete this survey. Your opinion is valuable to us. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from March 25th to March 31st, 2024 GPCR Activation and Signaling PACAP key interactions with PAC1, VPAC1, and VPAC2 identified by molecular dynamics simulations Preassembly of specific Gβγ subunits at GABAB receptors through auxiliary KCTD proteins accelerates channel gating TRPM5 activation depends on a synergistic effect of calcium and PKC phosphorylation After wounding, a G-protein coupled receptor promotes the restoration of tension in epithelial cells Profiling the proximal proteome of the activated μ-opioid receptor Computational modelling of dynamic cAMP responses to GPCR agonists for exploration of GLP-1R ligand effects in pancreatic β-cells and neurons GPCR Binders, Drugs, and more In silico identification of a biarylamine acting as agonist at human β3 adrenoceptors and exerting BRL37344-like effects on mouse metabolism Mechanistic insights into sodium ion-mediated ligand binding affinity and modulation of 5-HT2B GPCR activity: implications for drug discovery and development GPCRs in Neuroscience Scutellaria baicalensis Georgi stems and leaves flavonoids promote neuroregeneration and ameliorate memory loss in rats through cAMP-PKA-CREB signaling pathway based on network pharmacology and bioinformatics analysis Unveiling the therapeutic prospects of EGFR inhibition in rotenone-mediated parkinsonism in rats: Modulation of dopamine D3 receptor Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis GPCRs in Oncology and Immunology The β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells [Inhibitory effect of downregulating G protein-coupled receptor class C group 5 member A expression on lipopolysaccharide-induced inflammatory response in human gingival fibroblasts] Methods & Updates in GPCR Research Highly efficient GPCR immobilization with enhanced fouling resistance, salt tolerance, and chromatographic performance Fluorine-19 labeling of the tryptophan residues in the G protein-coupled receptor NK1R using the 5-fluoroindole precursor in Pichia pastoris expression Monitoring norepinephrine release in vivo using next-generation GRABNE sensors Reviews, GPCRs, and more Advances in GPCRs: Structure, Mechanisms, Disease, and Pharmacology Industry News Monash University pharmaceutical scientists honoured in NHMRC Research Excellence Awards Domain Therapeutics to Present Latest Data on DT-9045, a First-in-class Negative Allosteric Modulator of PAR2 for Immuno-oncology Crinetics Pharmaceuticals gets grant for patent granted for somatostatin modulators for treating hormone-related conditions Sosei Heptares Confirms Re-election of its Board and Executive Management Team and the Approval of Change of Company Name to Nxera Pharma Neurocrine Biosciences Announces Initiation of Phase 1 Clinical Study Evaluating Effects of NBI-1065890, a Second-Generation VMAT2 Inhibitor, in Healthy Adults Confo Therapeutics Secures VLAIO Grant Supporting Drug Discovery & Development In Endocrine And Metabolic Diseases How biotech companies are using AI to design drugs GPCR Therapeutics Announces Publication in PNAS Using Cutting Edge Spectroscopy to Detect GPCR Heteromers on Live Cancer Cells GPCR Events, Meetings, and Webinars April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Postdoctoral Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Join Dr. GPCR Ecosystem

GPCR activation typically occurs through the binding of agonists which stabilize receptor conformations that recruit and ultimately activate intracellular transducers. GPCRs are present in a range of conformations, and the binding of a ligand, as well as interactions with signaling molecules like G proteins, can selectively stabilize specific conformations (Gether 2000). In terms of pharmacology, GPCRs have been identified to exist in at least two distinct states: an active state characterized by high affinity for agonists when coupled to G proteins, and an inactive state in which their affinity for agonists diminishes in the absence of G proteins (Gether 2000), with numerous intermediate sub-states in between (Vauquelin and Van Liefde 2005; Yao et al. 2009). However, GPCRs are not simple on-off switches (Rosenbaum, Rasmussen, and Kobilka 2009), since they are able to adopt an active conformation without agonist engagement referred to as receptor constitutive or basal activity. The initial demonstration of spontaneous or "constitutive" receptor activity was reported for the β2-adrenergic receptor in 1984 (Cerione et al. 1984), where reconstitution of purified β2-adrenergic receptors from guinea pig lung in conjunction with purified Gαs from human erythrocytes led to an elevation in GTPase activity of Gαs without the presence of a ligand. Subsequently, opioid receptors were shown to constitutively activate Gi proteins in a membrane preparation without the need for an agonist (Costa and Herz 1989). GPCR ligands pharmacology The impact of a ligand on a receptor's structure and biophysical attributes, and consequently on the biological response, is referred to as ligand efficacy. Natural and synthetic ligands can be categorized into four distinct efficacy classes: 1) full agonists produce the maximal response and can differ in intrinsic efficacy; 2) partial agonists are incapable of inducing maximal activity even when they are present at saturating concentrations; 3) neutral antagonists have null intrinsic efficacy, thus not affecting receptor signaling activity, and can compete with agonist ligands; 4) and inverse agonists decrease the level of receptor constitutive activity. In the same way that agonists possess intrinsic efficacy, inverse agonists also exhibit varying degrees of negative intrinsic efficacy, leading to the presence of both robust and less potent (partial) inverse agonism (Rosenbaum, Rasmussen, and Kobilka 2009). GPCR targeting drugs: orthosteric vs allosteric sites Most of the drugs targeting GPCRs bind to the orthosteric site of the receptor, eliciting various effects, such as receptor activation (e.g., agonists or partial agonists), inhibition of activation (e.g., antagonists), or produce an inversion of the functional response (e.g., inverse agonists). Despite the existence of numerous drugs designed for this primary binding site, there are significant challenges in creating ligands that are both safe and effective. Those include the risk of unintended off-target effects, limited selectivity due to closely related receptor binding sites, the inability to target large and diffuse binding sites activated by peptides or proteins, and the disruption of natural spatial and temporal signaling patterns regulated by physiological systems (Wold and Zhou 2018). An alternative and promising approach is allosteric modulation. Allosteric binding sites on the receptor are those topographically distinct from (do not exhibit any overlap with) the orthosteric site (Rosenbaum, Rasmussen, and Kobilka 2009). Over the past decade, there has been a notable growth in the discovery of allosteric modulators for GPCRs which possess the capability to modulate and fine-tune the affinity and/or efficacy of orthosteric ligands. While this has the potential to enhance GPCR subtype-selectivity, it also presents a significant challenge when it comes to detecting and confirming allosteric behaviors (Keov, Sexton, and Christopoulos 2011). Compounds employing an allosteric mechanism of action can theoretically offer several advantages compared to orthosteric ligands when considered as potential therapeutic agents. Allosteric modulators that do not exhibit agonistic properties remain inactive in the absence of endogenous orthosteric activity, therefore having the potential to maintain the temporal and spatial aspects of natural physiological signaling. The significance of spatio-temporal attributes in signaling is demonstrated in processes like neurotransmission and chemokine signaling, extending to numerous other GPCR-regulated systems such as free fatty acid receptors (FFARs), now regarded as targets for therapeutic intervention for metabolic diseases such as liver disease, obesity and diabetes (Secor et al. 2021; Wold and Zhou 2018). Moreover, they have the potential to enhance target selectivity, which can arise from greater sequence variation in allosteric sites among receptor subtypes when compared to the conserved orthosteric region, or from selective cooperativity with a particular subtype while excluding others (Christopoulos 2002; Lazareno et al. 2004). This is particularly important when dealing with receptor subtypes that exhibit significant similarity in their orthosteric binding sites, such as chemokine receptors. On the other hand, selectivity could be achieved by merging both orthosteric and allosteric pharmacophores within a single compound, resulting in a novel category of GPCR ligands referred to as 'bitopic' (Valant et al. 2008). A third advantage is that they offer the prospect of reducing the risk of overdose, given that their activity is dependent on the concentration of the orthosteric ligand. In this context, allosteric modulators exhibiting constrained positive or negative cooperativity are characterized by having an upper limit on the extent of their allosteric influence, an attribute that offers a considerable degree of adjustability in terms of pharmacological effects, allowing for the administration of substantial doses of allosteric modulators with a diminished risk of target-related toxicity (Wold et al. 2018). GPCRs functional selectivity Recent research has revealed a more intricate understanding of GPCR behavior, extending beyond the traditional G-protein and second messenger activation pathways. Agonist binding to GPCRs doesn't always trigger all associated events sequentially. Depending on the specific functional outcome measured (e.g. activation, interaction with accessory proteins, dimerization, phosphorylation, internalization, or desensitization), the same drug acting on the same receptor in the same cellular context can produce a range of effects, from full activation to partial activation to inverse agonism. This variability in drug effects is due to different ligands inducing unique GPCR conformations that selectively activate specific cellular outcomes linked to that GPCR. This phenomenon is termed "stimulus-trafficking," "biased agonism," or "functional selectivity" (Urban et al. 2007). Overall, GPCRs are intriguing molecules that deviate from typical textbook proteins. They do not have a binary active or inactive state but instead can adopt numerous distinct conformational states, each of which triggers a distinct array of physiological effects. They can be compared to molecular rheostats, capable of sampling a spectrum of conformations with relatively small energy differences (Ma, Lee, and Vaidehi 2020). The ligand alters the balance of these conformations, increasing the prevalence of some infrequent ones, preventing access to others, or allowing previously inaccessible conformations. To understand how ligands or drugs affect GPCRs is crucial to grasp the dynamics of these conformational shifts and identify the most relevant forms.

Hello readers! BIG NEWS! Check out our GPCR coverage for this week. We have 15 GPCR papers and four industry news. This week's highlight includes congrats to: Drs. Miles Thompson, Alexander Hauser, Caroline Gorvin et al. for their research on GPCR gene variants and human genetic disease. Dr. GPCR Symposia With a premium membership, you can watch on-demand the Dr. GPCR Symposium on GPCR activation and signaling sessions. Our next symposium on Structural and Molecular Insights into GPCR Function. is scheduled for June 7th. Stay tuned for more updates. If you want to showcase your research, you can submit a poster presentation to our community, take advantage of networking opportunities, and raise your profile on our platform. Get started by filling out this form! If you have a few minutes to spare and have participated in our symposiums, we would appreciate it if you could complete this survey. Your opinion is valuable to us. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from March 18th to 24th, 2024 GPCR Activation and Signaling Calcium-Driven In Silico Inactivation of a Human Olfactory Receptor Deciphering the role of glycosaminoglycans in GPCR signaling G protein-coupled receptor-mediated autophagy in health and disease GPCR Binders, Drugs, and more Elucidation of active components and target mechanism in Jinqiancao granules for the treatment of prostatitis and benign prostatic hyperplasia GPCRs in Cardiology, Endocrinology, and Taste Blockade of endothelial adenosine receptor 2A suppresses atherosclerosis in vivo through inhibiting CREB-ALK5-mediated endothelial to mesenchymal transition Role of pH-sensing receptors in colitis GPCRs in Oncology and Immunology Polarizing itch Biochemical pharmacology of adenylyl cyclases in cancer Methods & Updates in GPCR Research A multicolor suite for deciphering population coding of calcium and cAMP in vivo Cryo-EM advances in GPCR structure determination Visualization of endogenous G proteins on endosomes and other organelles Reviews, GPCRs, and more G protein-coupled receptor (GPCR) gene variants and human genetic disease Advances and challenges in cancer immunoprevention and immune interception Structural and Molecular Insights into GPCR Function Structural bioinformatics studies of serotonin, dopamine and norepinephrine transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F Industry News Sosei Heptares Doses First Subject in Phase 1 Trial with HTL0033744, an EP4 Agonist for Inflammatory Bowel Disease (IBD) Domain Therapeutics and Chime Biologics Form Manufacturing Pact for Antibody Cancer Immunotherapy Sosei Heptares Regains Full Ownership from GSK of HTL0027477, a Clinic-ready, First-in-Class Oral GPR35 Agonist for Inflammatory Bowel Disease Crinetics’ Once-Daily Oral Paltusotine Achieved The Primary And All Secondary Endpoints In The Phase 3 Pathfndr-2 Study In Acromegaly Patients GPCR Events, Meetings, and Webinars March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Postdoctoral Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Join Dr. GPCR Ecosystem

Hello readers! We had an amazing week. Don’t miss out on our GPCR coverage for this week. We have 10 GPCR papers, five industry news, and one job ad. This week's highlight includes congrats to: Makaía M Papasergi-Scott, Peter Gmeiner, Brian K Kobilka, Georgios Skiniotis, et al. for their research on Time-resolved cryo-EM of G-protein activation by a GPCR Remi Janicot, Alex Luebbers, Mikel Garcia-Marcos, et al. for their work on Direct interrogation of context-dependent GPCR activity with a universal biosensor platform Dr. GPCR Symposia We extend our heartfelt thanks to all speakers and participants for making our recent Dr. GPCR Symposium on GPCR activation and signaling a resounding success! If you missed it, don't worry – you can catch the sessions on-demand with a premium membership. Exciting news awaits! We're gearing up for our next symposium on June 7th, focusing on Structural and Molecular Insights into GPCR Function. Stay tuned for more information coming soon. Interested in showcasing your research? Submit a poster presentation to our community, seize networking opportunities, and elevate your profile on our platform. Simply fill out this form to get started! Are you free for a few minutes? If you participated in our symposiums, please take a moment to complete this survey. Your opinion is valuable to us. Dr. GPCR University Save the date for our upcoming workshop, starting May 9th, 2024, featuring Dr. Sam Hoare as our instructor. Under Dr. Hoare's expert guidance, you will gain invaluable skills in data analysis. More details are coming soon—stay tuned! Dr. Terry Kenakin's "Applying Pharmacology to Drug Discovery" course at Dr. GPCR University was tremendously successful. If you're eager to attend, join our waitlist for updates on its return later this year. Those on the waitlist will be notified first of the course dates, so hurry. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from March 11th to 17th, 2024 Adhesion GPCRs ADGRG1, an adhesion G protein-coupled receptor, forms oligomers GPCR Activation and Signaling Unraveling the crosstalk between renin-angiotensin system receptors Arrestin-centred interactions at the membrane and their conformational determinants The polybasic region in Gαi proteins: Relevant or not? Insights from Gαi3 research GPCRs in Cardiology, Endocrinology, and Taste The Prostaglandin E2 EP3 Receptor Has Disparate Effects on Islet Insulin Secretion and Content in β-cells in a High Fat Diet-induced Mouse Model of Obesity GPCRs in Neuroscience Xanthurenic acid: A role in brain intercellular signaling Are there sex differences in oxytocin and vasopressin V1a receptors ligand binding affinities? Methods & Updates in GPCR Research Direct interrogation of context-dependent GPCR activity with a universal biosensor platform Protocol to visualize and quantify the COPII concentration and anterograde transport of nascent G protein-coupled receptors Structural and Molecular Insights into GPCR Function Time-resolved cryo-EM of G-protein activation by a GPCR Industry News Domain Therapeutics and Chime Biologics announce manufacturing agreement  to advance novel anti-CCR8 antibody  for cancer immunotherapy Novo Holdings Portfolio Company Amolyt Pharma Enters into Definitive Agreement to be Acquired by AstraZeneca Basecamp Research Launches BaseFold: A Breakthrough in 3D Protein Structure Prediction of Large, Complex Protein Structures Newly discovered adhesion GPCR mayo controls midgut development in Drosophila Karuna Therapeutics announces that is now part of Bristol Myers Squibb GPCR Events, Meetings, and Webinars March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Associate Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Join Dr. GPCR Ecosystem

Hi readers! Get the latest updates on breakthroughs in GPCR research with our concise and comprehensive summaries. Stay ahead of the curve! This week's highlight includes congrats to Drs. Khaled Abd-Elrahman, Stephen Ferguson et al. Their research reveals how VU0486846 reduces neurogliosis in female Alzheimer's mice. Dr. GPCR Symposia TOMORROW, we are hosting a symposium on GPCR activation and signaling. We are pleased to confirm the participation of a great lineup of speakers, namely Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, Cesare Orlandi, Simone Prömel and Michel Bouvier. Additionally, we are having a Panel Discussion on Publishing in Academia with Drs. Stuart Maudsley, Nicole Perry-Hauser, Lauren Slosky, Cesare Orlandi, and Simone Prömel. Please note that we moved our clocks ahead in North America. If you are joining from anywhere else in the world, please plan accordingly. Don't miss out, and mark your calendar! Dr. GPCR University Save the date for our upcoming workshop starting May 9th, 2024, featuring Dr. Sam Hoare as our instructor. Gain invaluable skills in data analysis under Dr. Hoare's expert guidance. More details are coming soon—stay tuned! Dr. Terry Kenakin's "Applying Pharmacology to Drug Discovery" course at Dr. GPCR University was tremendously successful. If you're eager to attend, join our waitlist for updates on its return later this year. Those on the waitlist will be the first notified of the course dates, so hurry. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from March 4th to 10th, 2024 GPCR Activation and Signaling Glu1022.53-Mediated Early Conformational Changes in the Process of Light-Induced Green Cone Pigment Activation Molecular dynamics-based identification of binding pathways and two distinct high-affinity sites for succinate in succinate receptor 1/GPR91 Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors GPCRs in Neuroscience A M1 muscarinic acetylcholine receptor-specific positive allosteric modulator VU0486846 reduces neurogliosis in female Alzheimer's mice The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function Interaction modes of human orexin 2 receptor with selective and nonselective antagonists studied by NMR spectroscopy Up-regulation of GPR139 in the medial septum ameliorates cognitive impairment in two mouse models of Alzheimer's disease GPCRs in Oncology and Immunology Itaconate in host inflammation and defense Methods & Updates in GPCR Research Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo Reviews, GPCRs, and more 2023 Julius Axelrod Symposium: Plant-derived molecules acting on GPCRs Molecular characterization of recombinant LSDV isolates from 2022 outbreak in Indonesia through phylogenetic networks and whole-genome SNP-based analysis Industry News Boehringer Ingelheim and Sosei Heptares join forces to develop first-in-class treatments targeting all symptoms of schizophrenia Sosei Heptares to receive US$2.5 million milestone payment from Formosa Pharmaceuticals Are GLP-1s finding the right balance in obesity? Deciphering the role of GPCRs in obesity pathology for drug development GPCR Events, Meetings, and Webinars March 13 - 15 | Biologics 2024 March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Research Technologist I Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Postdoctoral Fellowship- Mechanistic Biology Join Dr. GPCR Ecosystem

Welcome to our weekly GPCR Newsletter - your source for the latest insights, breakthroughs, and updates! This week's highlight includes congrats to: Christina Katharina Kuhn, Drs. Sandra Berndt, Ines Liebscher, and Susanne Horn et. al for their for their research on adhesion GPCR transcript variants from publicly available human samples. Howard Rockman, and Dr. Robert Lefkowitz for their work on GPCRs: from radioligand binding to cellular signaling Dr. GPCR Symposia Mark your calendars! Next week, on March 15th, we are hosting a symposium on GPCR activation and signaling. We are delighted to confirm the participation of esteemed speakers such as Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, Cesare Orlandi, Simone Prömel and Michel Bouvier. Additionally, we will be hosting a poster session in Zoom breakout rooms. If you want to share your work with our community, please don’t hesitate to fill out this form. We also value your feedback. If you attended our 2023 Symposia, please take a moment to complete this survey. Dr. GPCR University Great News! The Dr. GPCR University Course, ‘Applying Pharmacology to Drug Discovery,’ led by Dr. Terry Kenakin, was a resounding success; we have a waitlist for those eager to attend this course, which wil be coming back later this year. Mark your calendar; we’re planning a workshop for May 2024 with Dr. Sam Hoare as our instructor. With Dr. Hoare, you’ll learn how to analyze your data like a pro. Stay tuned for more information. Dr. GPCR Partnered Events April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from February 26th to March 3rd, 2024 Adhesion GPCRs The repertoire and structure of adhesion GPCR transcript variants assembled from publicly available deep-sequenced human samples GPCR Activation and Signaling Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution G protein-coupled receptors: from radioligand binding to cellular signaling GPR101: Modeling a constitutively active receptor linked to X-linked acrogigantism State-dependent dynamics of extramembrane domains in the β2 -adrenergic receptor β-Arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR Bias translation: The final frontier? Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury GPCRs in Cardiology, Endocrinology, and Taste RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms Phenylacetyl glutamine (PAGln) enhances cardiomyocyte death after myocardial infarction through β1 adrenergic receptor GPCRs in Neuroscience Discovery of potential TAAR1 agonist targeting neurological and psychiatric disorders: An in silico approach Opioid modulation of prefrontal cortex cells and circuits GPCRs in Oncology and Immunology RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells Methods & Updates in GPCR Research Cryo-electron microscopy for GPCR research and drug discovery in endocrinology and metabolism Reviews, GPCRs, and more Butyrate as a promising therapeutic target in cancer: From pathogenesis to clinic (Review) Will the hype of automated drug discovery finally be realized? Commentary: Analyzing invertebrate bitopic cadherin G protein-coupled receptors that bind cry toxins of Bacillus thuringiensis Industry News Domain Therapeutics announces the promotion of Stephan Schann to the role of Chief Scientific Officer Crinetics Reports Fourth Quarter And Full Year 2023 Financial Results And Provides Corporate Update. Biagon Officially Incorporated In The State Of Illinois Septerna divulges new TSHR antagonists for hyperthyroidism Unlocking the Secrets of Cellular Communication: The Revolutionary Impact of Cryo-EM on GPCR Research GPCR Events, Meetings, and Webinars March 13 - 15 | Biologics 2024 March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 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 Senior Scientist- Internal Medicine Research Unit Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Postdoctoral Fellowship- Mechanistic Biology Research Scientist Join Dr. GPCR Ecosystem

When it comes to signal transduction, cellular context matters. The cellular context is crucial for understanding the diverse signaling outcomes mediated by different receptors including G protein coupled receptors (GPCRs). The localization of GPCRs to specific intracellular compartments dictates the spatial and temporal dynamics of signaling, ultimately shaping cellular responses1. For example, the lipid composition of intracellular membranes may influence GPCR dynamics and signaling outcomes, changing the receptor conformation and accessibility to ligands2. Traditionally, GPCR signaling was believed to primarily occur at the plasma membrane. However, emerging evidence suggests that GPCRs also signal from intracellular membranes including endosomes, the Golgi apparatus, and the nuclear membrane, leading to spatially biased signaling responses. In the endosomes, sustained G protein signaling has been associated with prolonged interactions between GPCRs, G proteins, and arrestins on endosomal membranes3,4. This phenomenon has been demonstrated for receptors such as the parathyroid hormone receptor (PTHR) and the vasopressin receptor 2 (V2R). The formation of stable complexes between GPCRs and signaling effectors on endosomes supports multiple rounds of G protein activation, leading to sustained cellular responses5,6. The role of β-arrestins in endosomal signaling has been extensively studied, highlighting their ability to scaffold various kinases and modulate downstream signaling pathways. Showing that this spatially biased signaling through arrestins can influence transcriptional responses and contribute to physiological processes such as meiosis in ovarian follicles and pain neurotransmission7,1. In addition to endosomal signaling, GPCRs are also known to localize to the Golgi apparatus, where they can be activated by ligands and initiate signaling cascades. The Golgi-localized signaling of GPCRs such as the β1-adrenergic receptor (B1AR) and the thyroid-stimulating hormone receptor (TSHR) has been shown to regulate distinct cellular processes, including phospholipase C epsilon (PLCε)-dependent signaling and transcriptional responses mediated by CREB phosphorylation1,8,9. Furthermore, GPCRs localized to the nuclear membrane have emerged as important regulators of gene transcription and cellular responses. Activation of nuclear GPCRs, such as the metabotropic glutamate receptor 5 (mGluR5), can lead to sustained calcium signaling and activation of transcription factors like CREB and Elk1, influencing synaptic plasticity and neuronal function10. GPCRs have also been identified within the mitochondria. Initial investigations revealed the positioning of the cannabinoid CB1 receptor on the outer mitochondrial membrane of skeletal and myocardial cells, where stimulation of mitochondrial CB1 receptors by lipophilic agonists in these tissues was associated with the modulation of oxidative activity via enzymes involved in pyruvate metabolism11. As the mechanisms underlying spatial bias in GPCR signaling involve both temporal and spatial components, sustained signaling responses from intracellular compartments can be regulated by the kinetics of signaling and the spatial organization of signaling effectors, including G proteins, adenylyl cyclases, and kinases. Therefore the presence of membrane microdomains and protein scaffolds, further contributes to the spatial regulation of GPCR signaling and downstream responses1,2. The clinical relevance of understanding these signaling mechanism is linked with the fact that dysregulation of compartmentalized GPCR signaling has been implicated in various diseases. For instance, aberrant endosomal signaling by GPCRs has been linked to disorders such as cancer, neurodegenerative diseases, and cardiovascular disorders. Therefore, targeting specific intracellular compartments and signaling pathways associated with GPCRs holds promise for the development of novel therapeutic interventions12. Tagging GPCRs expressed in cellular compartments such as the nucleus or endosomes presents several pharmaceutical challenges for many reasons. These compartments have distinct biochemical environments, which may affect the stability and functionality of the tagging molecules. For example, the nuclear envelope presents a barrier that restricts the passage of large molecules, making it challenging to deliver tagging agents effectively. Additionally, the conditions within endosomes, such as low pH and high protease activity, can degrade tagging molecules, reducing their effectiveness1,8,12. Furthermore, targeting GPCRs in specific cellular compartments requires precise delivery mechanisms to ensure the tagging molecules reach their intended destination. This may involve the development of specialized delivery vehicles, such as nanoparticles or liposomes, capable of penetrating cellular membranes and delivering the tagging agents to the desired compartment. Another challenge is the potential interference of tagging molecules with GPCR function. Tagging molecules may alter the conformation or activity of GPCRs, leading to unintended effects on downstream signaling pathways. Therefore, it is essential to design tagging strategies that minimize interference with GPCR function while allowing for accurate detection and localization. Overall, the pharmaceutical challenges associated with tagging GPCRs expressed in cellular compartments require innovative approaches to overcome barriers related to stability, delivery, interference with GPCR function, and off-target effects. References Crilly, S. E., & Puthenveedu, M. A. (2021). Compartmentalized GPCR Signaling from Intracellular Membranes. The Journal of membrane biology, 254(3), 259–271. https://doi.org/10.1007/s00232-020-00158-7 Gonçalves-Monteiro, S., Ribeiro-Oliveira, R., Vieira-Rocha, M. S., Vojtek, M., Sousa, J. B., & Diniz, C. (2021). Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases. Pharmaceuticals (Basel, Switzerland), 14(5), 439. https://doi.org/10.3390/ph14050439 Chen, K. E., Healy, M. D., & Collins, B. M. (2019). Towards a molecular understanding of endosomal trafficking by Retromer and Retriever. Traffic (Copenhagen, Denmark), 20(7), 465–478. https://doi.org/10.1111/tra.12649 Ribeiro-Oliveira, R., Vojtek, M., Gonçalves-Monteiro, S., Vieira-Rocha, M. S., Sousa, J. B., Gonçalves, J., & Diniz, C. (2019). Nuclear G-protein-coupled receptors as putative novel pharmacological targets. Drug discovery today, 24(11), 2192–2201. https://doi.org/10.1016/j.drudis.2019.09.003 Ferrandon, S., Feinstein, T. N., Castro, M., Wang, B., Bouley, R., Potts, J. T., Gardella, T. J., & Vilardaga, J. P. (2009). Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nature chemical biology, 5(10), 734–742. https://doi.org/10.1038/nchembio.206 Wei, H., Ahn, S., Shenoy, S. K., Karnik, S. S., Hunyady, L., Luttrell, L. M., & Lefkowitz, R. J. (2003). Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proceedings of the National Academy of Sciences of the United States of America, 100(19), 10782–10787. https://doi.org/10.1073/pnas.1834556100 Lyga, S., Volpe, S., Werthmann, R. C., Götz, K., Sungkaworn, T., Lohse, M. J., & Calebiro, D. (2016). Persistent cAMP Signaling by Internalized LH Receptors in Ovarian Follicles. Endocrinology, 157(4), 1613–1621. https://doi.org/10.1210/en.2015-1945 Irannejad, R., Pessino, V., Mika, D., Huang, B., Wedegaertner, P. B., Conti, M., & von Zastrow, M. (2017). Functional selectivity of GPCR-directed drug action through location bias. Nature chemical biology, 13(7), 799–806. https://doi.org/10.1038/nchembio.2389 Godbole, A., Lyga, S., Lohse, M. J., & Calebiro, D. (2017). Internalized TSH receptors en route to the TGN induce local Gs-protein signaling and gene transcription. Nature communications, 8(1), 443. https://doi.org/10.1038/s41467-017-00357-2 Jong, Y. I., & O'Malley, K. L. (2017). Mechanisms Associated with Activation of Intracellular Metabotropic Glutamate Receptor, mGluR5. Neurochemical research, 42(1), 166–172. https://doi.org/10.1007/s11064-016-2026-6 Mendizabal-Zubiaga, J., Melser, S., Bénard, G., Ramos, A., Reguero, L., Arrabal, S., Elezgarai, I., Gerrikagoitia, I., Suarez, J., Rodríguez De Fonseca, F., Puente, N., Marsicano, G., & Grandes, P. (2016). Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration. Frontiers in physiology, 7, 476. https://doi.org/10.3389/fphys.2016.00476 Insel, P. A., Sriram, K., Wiley, S. Z., Wilderman, A., Katakia, T., McCann, T., Yokouchi, H., Zhang, L., Corriden, R., Liu, D., Feigin, M. E., French, R. P., Lowy, A. M., & Murray, F. (2018). GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets. Frontiers in pharmacology, 9, 431. https://doi.org/10.3389/fphar.2018.00431

Hello readers! Check out our GPCR coverage for this week. We have 19 GPCR papers, six industry news, two events, and two job ads. This week's highlight includes congrats to: Johanna Lena Schön, and Dr. Simone Prömel et al. for their study on the effect of Flamingo (FMI-1) on body size and extracellular matrix. Isabella Russell, Drs. Patrick Sexton, and Matthew Belousoff et al. for their work on Lipid-Dependent Activation of the Orphan G Protein-Coupled Receptor GPR3 Dr. GPCR Symposia Mark your calendars! In just two weeks, on March 15th, we are hosting a symposium on GPCR activation and signaling. We are delighted to confirm the participation of esteemed speakers such as Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, Cesare Orlandi, Simone Prömel and Michel Bouvier. Additionally, we will be conducting a poster session in Zoom breakout rooms. If you want to share your work with our community, please don’t hesitate to fill out this form. We also value your feedback. If you attended our 2023 Symposia, please take a moment to complete this survey. Dr. GPCR University Today marks the conclusion of the Dr.GPCR University course, ‘Applying Pharmacology to Drug Discovery,’ expertly led by Dr. Terry Kenakin. We would like to extend our heartfelt thanks to Dr. Kenakin for his invaluable contributions and to all the participants for their active involvement and enthusiasm. If you were interested in this course but missed the opportunity to register, fret not! You can still sign up for our waitlist. We will be offering this live course again later this year. By being on the waitlist, you’ll be the first to be notified when official registrations open for the next session. Dr. GPCR Volunteers Join our dynamic team as a volunteer! You'll share your contributor articles with the community, stay updated with GPCR literature, join a dynamic team, network with GPCR scientists at our events, and get a complimentary Premium Membership with only 4 hours/monthly commitment on your part. If you are interested in applying, please email us your CV/Resume at  Hello@DrGPCR.com. Dr. GPCR Partnered Events March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit. Join Dr. GPCR Founder Dr. Yamina Berchiche at the 3rd GPCRs Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10. April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join Dr. GPCR Founder Dr. Yamina Berchiche at the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from  February 19th to 25th, 2024 Adhesion GPCRs The Adhesion GPCR and PCP component Flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix GPCR Activation and Signaling Probing Activation and Conformational Dynamics of the Vesicle-Reconstituted β2 Adrenergic Receptor at the Single-Molecule Level Pharmacological characterization of seven human histamine H3 receptor isoforms Lipid-Dependent Activation of the Orphan G Protein-Coupled Receptor, GPR3 After wounding, a G-protein coupled receptor promotes the restoration of tension in epithelial cells GPCR Binders, Drugs, and more Advances in structure-based drug design: The potential for precision therapeutics in psychiatric disorders Discovery of a Photoaffinity Probe that Captures the Active Conformation of the Cannabinoid CB2 Receptor GPCRs in Neuroscience G protein-coupled receptor-based thermosensation determines temperature acclimatization of Caenorhabditis elegan Species-Specific Duplicated FMRFaR-like Gene A62 Regulates Spontaneous Locomotion in Apolygus lucorum Whole Brain Mapping of Orexin Receptor mRNA Expression Visualized by Branched In Situ Hybridization Chain Reaction Orphan GPR52 as an emerging neurotherapeutic target Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons GPCRs in Oncology and Immunology TIPE proteins control directed migration of human T cells by directing GPCR and lipid second messenger signaling Methods & Updates in GPCR Research A bioluminescent and homogeneous assay for monitoring GPCR-mediated cAMP modulation and PDE activity GPCRs in the round: SMA-like copolymers and SMALPs as a platform for investigating GPCRs Reviews, GPCRs, and more Fragment-Based Design, Synthesis, and Characterization of Aminoisoindole-Derived Furin Inhibitors A Bright Future? A Perspective on Class C GPCR Based Genetically Encoded Biosensors Emergence of lumpy skin disease virus (LSDV) infection in domestic Himalayan yaks (Bos grunniens) in Himachal Pradesh, India Structural and Molecular Insights into GPCR Function Exploring Diverse Signaling Mechanisms of G Protein-Coupled Receptors through Structural Biology Industry News INV-347 by Inversago Pharma for Obesity: Likelihood of Approval Septerna to Participate in Upcoming Investor and Industry Conferences Sosei and IPJ to become Nxera Pharma from April Orion Biotechnology will be at the BIO CEO & Investor Conference Salipro Biotech AB will be at the Oxford Global’s Biologics event GPCR Events, Meetings, and Webinars February 20, 2024 | Career Opportunities in Pharmacology and Drug Discovery NEW March 13 - 15 | Biologics 2024 March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 2024 NEW 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 Senior Scientist- Internal Medicine Research Unit NEW Postdoctoral Scholar – Synaptic physiology, optical imaging, substance use disorder, pharmacology Research Fellow Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Postdoctoral Fellowship- Mechanistic Biology Research Scientist Join Dr. GPCR Ecosystem

Greetings, avid readers! We are thrilled to present our comprehensive GPCR coverage for the week; we have 14 GPCR papers, six industry news, and two job ads. This week's highlight includes congrats to Julia Gardner, Dr. Dylan Scott Eiger, Chloe Hicks,  Dr. Sudarshan Rajagopal, et al. for their finding that GPCR kinases affect biased signaling downstream of CXCR3 based on their location. Drs. Nayara Braga Emidio, Ross Cheloha, Laura M Wingler, et al. for their work on Nanobody-Mediated Dualsteric Engagement. Dr. GPCR Symposia Our upcoming symposium on March 15th is about GPCR activation and signaling. Confirmed speakers include Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, and Michel Bouvier. We will also have a poster session in breakout rooms on Zoom; if you are interested in sharing your work with our community, kindly fill out this form. Additionally, if you participated in our Symposia in 2023, please take a moment to fill out this survey. Dr. GPCR University The past two weeks of the Dr. GPCR University course, 'Applying Pharmacology to Drug Discovery,' led by Dr. Terry Kenakin, have been amazing. Attendees have actively participated in discussions and asked thought-provoking questions. If you missed the chance to register, don't worry! You can still join this waitlist and be the first to know when the live course is offered later this year. Dr. GPCR Volunteers Join our dynamic team as a volunteer! You'll share your contributor articles with the community, stay updated with GPCR literature, join a dynamic team, network with GPCR scientists at our events, and get a complimentary Premium Membership with only 4 hours/monthly commitment on your part. If you are interested in applying, please email us your CV/Resume at  Hello@DrGPCR.com. Dr. GPCR Partnered Events March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit Join us at the 3rd GPCRs Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10. April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join Dr. GPCR founder Dr. Yamina Berchiche at the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from February 12th to 18th, 2024 GPCR Activation and Signaling Fine-tuning activation specificity of G-protein-coupled receptors via automated path searching Heterotrimeric G protein signaling without GPCRs: the Gα-binding-and-activating (GBA) motif Mechanisms of biased agonism by Gαi/o-biased stapled peptide agonists of the relaxin-3 receptor GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization Investigating selectivity and bias for G protein subtypes and β-arrestins by synthetic cannabinoid receptor agonists at the cannabinoid CB1 receptor Why classical receptor theory, which ignores allostery, can effectively measure the strength of an allosteric effect as agonist's efficacy GPCR Binders, Drugs, and more Nanobody-Mediated Dualsteric Engagement of the Angiotensin Receptor Broadens Biased Ligand Pharmacology Pharmacological characterization and radiolabeling of VUF15485, a high-affinity small-molecule agonist for the atypical chemokine receptor ACKR3 GPCRs in Cardiology, Endocrinology, and Taste The Role of G Protein-Coupled Receptors and Receptor Kinases in Pancreatic β-Cell Function and Diabetes GPCRs in Neuroscience Voltage tunes mGlu5 receptor function, impacting synaptic transmission The multifaceted role of the CXC chemokines and receptors signaling axes in ALS pathophysiology Common changes in rat cortical gene expression after antidepressant drug treatment: impacts on metabolism of polyamines, mRNA splicing, regulation of RAS by GAPs, neddylation and GPCR ligand binding GPCRs in Oncology and Immunology Neutrophils are itching to specialize A GPCR-neuropeptide axis dampens hyperactive neutrophils by promoting an alternative-like polarization during bacterial infection Industry News InterAx Biotech's AI platform unlocks new drug designs for diabetes, obesity, and cancer Crinetics Pharmaceuticals to Report Fourth Quarter and Full Year 2023 Financial Results on February 28, 2024 Sosei Heptares Operational Highlights and Consolidated Results for 12 Months ended 31 December 2023 Pioneering Research in GPCR Pharmacology: Unraveling the Secrets of Cellular Communication Bowes Biomedical Investigator Takes Aim at Cracking Cellular Communication Code Aelis Farma will be at Bio Europe Spring in Barcelona GPCR Events, Meetings, and Webinars February 20, 2024 | Career Opportunities in Pharmacology and Drug Discovery March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Research Fellow NEW  Postdoctoral Fellow – Molecular Pharmacology of Feeding Behavior Director of Laboratory Operations - Single-molecule Imaging Center Scientific Assistant Postdoctoral Fellowship- Mechanistic Biology Research Scientist Post-Doc position Join Dr. GPCR Ecosystem

Hi readers! Check out our GPCR coverage for this week. We have 10 GPCR papers, six industry news, and two job ads. This week's highlight includes congrats to: Drs. Magdalena M Scharf, Antonella Di Pizio, Ines Liebscher, Hannes Schihada, and Gunnar Schulte et al. on their study on understudied GPCRs and their dark sides. Dr. GPCR Symposia Our upcoming symposium on March 15th is about GPCR activation and signaling. Confirmed speakers include Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, Cesare Orlandi and Michel Bouvier. We will also have a poster session in breakout rooms on Zoom; if you are interested in sharing your work with our community, kindly fill out this form. Additionally, if you participated in our Symposia in 2023, please take a moment to fill out this survey. Dr. GPCR University Last week marked the beginning of our first Dr.GPCR University course, 'Applying Pharmacology to Drug Discovery, led by Dr. Terry Kenakin. If you are interested in joining this course but missed the registration window, don't worry! You can sign up for our waitlist. We will be offering this live course later this year. If you are on the waitlist, you'll be the first notified and can register for the course ahead of everyone else. Dr. GPCR Volunteers Join our dynamic team as a volunteer! You'll share your contributor articles with the community, stay updated with GPCR literature, network with GPCR scientists at our events, and get a complimentary Premium Membership with only 4 hours/monthly commitment on your part. If you are interested in applying, please email us your CV/Resume at  Hello@DrGPCR.com. Dr. GPCR Partnered Events March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit Join us at the 3rd GPCRs Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10. April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join our Founder Dr. Yamina Berchiche at the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from February 5th to 11th, 2024 GPCR Activation and Signaling Constitutive activation mechanism of a class C GPCR Allosteric modulation and G-protein selectivity of the Ca2+-sensing receptor GPCRs in Cardiology, Endocrinology, and Taste G protein-coupled receptors driven intestinal glucagon-like peptide-1 reprogramming for obesity: Hope or hype? Doxorubicin alters G-protein coupled receptor-mediated vasocontraction in rat coronary arteries GPCRs involved in metabolic diseases: pharmacotherapeutic development updates Methods & Updates in GPCR Research GPCR-BERT: Interpreting Sequential Design of G Protein-Coupled Receptors Using Protein Language Models Scaling up Functional Analyses of the G Protein-Coupled Receptor Rhodopsin Reviews, GPCRs, and more The dark sides of the GPCR tree - research progress on understudied GPCRs Structural and Molecular Insights into GPCR Function GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway Unraveling the Interplay of Extracellular Domain Conformational Changes and Parathyroid Hormone Type 1 Receptor Activation in Class B1 G Protein-Coupled Receptors: Integrating Enhanced Sampling Molecular Dynamics Simulations and Markov State Models Industry News Exscientia Initiates Clinical Study to Further Evaluate Functional Precision Medicine Platform in Cancer Patients Orion Biotechnology to Showcase GPCR Progress at 2024 OBIO Investment Summit BioAge raises $170M as obesity spotlight shifts to oral options, muscle preservers Neurocrine Biosciences Reports Fourth Quarter and Fiscal 2023 Financial Results and Provides Financial Expectations for 2024 Domain Therapeutics further strengthens leadership team with appointment of Sean A. MacDonald as Chief Business Officer. Septerna Appoints Industry Veterans Bernard Coulie, M.D., Ph.D., and Shalini Sharp to its Board of Directors GPCR Events, Meetings, and Webinars February 20, 2024 | Career Opportunities in Pharmacology and Drug Discovery March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Director of Laboratory Operations - Single-molecule Imaging Center NEW Scientific Assistant Postdoctoral Fellowship- Mechanistic Biology Research Scientist Post-Doc position Lead Researcher Join Dr. GPCR Ecosystem

Hello readers! Check out our GPCR coverage for this week. We have 21 GPCR papers, three industry news, and two job ads. This week's highlight includes congrats to: Gabriele Kockelkoren, Dr. Dimitrios Stamou, et al. for their work on the Molecular mechanism of GPCR spatial organization at the plasma membrane, featured on the cover of Nature Chemical Biology Julia Kinsolving; Dr. Gunnar Schulte et al. on the study of the interaction of Clostridioides difficile toxin B and FZD7. Preston Nibley, Dr. Sudha K Shenoy et al. on their work entitled β-arrestins and their potential role in heart failure. Dr. Xavier Leroy for his new role as CEO of GIO Therapeutics Dr. GPCR Symposia Our upcoming symposium on March 15th is about GPCR activation and signaling. Confirmed speakers include Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, and Michel Bouvier. We will also have a poster session in breakout rooms on Zoom; if you are interested in sharing your work with our community, kindly fill out this form. Additionally, if you participated in our Symposia in 2023, please take a moment to fill out this survey. Dr. GPCR University This week marks the beginning of our first Dr.GPCR University course, 'Applying Pharmacology to Drug Discovery,' which will be led by Dr. Terry Kenakin. If you are interested in joining this course but missed the registration window, don't worry! You can sign up for our waitlist. We are considering rerunning this live course later this year. If you are on the waitlist, you'll be the first notified, and you'll be able to register for the course official registrations open. Dr. GPCR Volunteers Join our dynamic team as a volunteer! You'll share your contributor articles with the community, stay updated with GPCR literature, join a dynamic team, network with GPCR scientists at our events, and get a complimentary Premium Membership with only 4 hours/monthly commitment on your part. If you are interested in applying, please email us your CV/Resume at  Hello@DrGPCR.com. Dr. GPCR Partnered Events March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit Join us at the 3rd GPCRs Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10. April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Let’s dive into the Classified GPCR News from January 29th to February 4th, 2024 Adhesion GPCRs CELSR1, a core planar cell polarity protein, features a weakly adhesive and flexible cadherin ectodomain GPCR Activation and Signaling GPCR signaling bias: an emerging framework for opioid drug development Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD7 Loss-of-function of GNAL dystonia gene impairs striatal dopamine receptors-mediated adenylyl cyclase/ cyclic AMP signaling pathway The non-nutritive sweetener sucralose increases β-arrestin signaling at the constitutively active orphan G protein-coupled receptor GPR52 Endosome positioning coordinates spatially selective GPCR signaling GRK5 promoted renal fibrosis via HDAC5/Smad3 signaling pathway Non-canonical G protein signaling GPCR Binders, Drugs, and more Insights on discovery, efficacy, safety and clinical applications of ghrelin receptor agonist capromorelin in veterinary medicine GPCRs in Cardiology, Endocrinology, and Taste The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure GPCRs in Neuroscience Role of lipids in the control of autophagy and primary cilium signaling in neurons The structure and function of olfactory receptors GPCRs in Oncology and Immunology Natural carboxyterminal truncation of human CXCL10 attenuates glycosaminoglycan binding, CXCR3A signaling and lymphocyte chemotaxis, while retaining angiostatic activity GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment Drosophila cytokine GBP2 exerts immune responses and regulates GBP1 expression through GPCR receptor Mthl10 Methods & Updates in GPCR Research Engineering, applications, and future perspectives of GPCR-based genetically encoded fluorescent indicators for neuromodulators Illuminating the brain-genetically encoded single wavelength fluorescent biosensors to unravel neurotransmitter dynamics MFD-GDrug: multimodal feature fusion-based deep learning for GPCR-drug interaction prediction Structural and Molecular Insights into GPCR Function Structural insights into membrane adenylyl cyclases, initiators of cAMP signaling Molecular mechanism of GPCR spatial organization at the plasma membrane Industry News Launch of GIO Therapeutics, founded by Cumulus Oncology, to develop therapeutics targeting G protein-coupled receptors to treat cancer and inflammation AVROBIO and Tectonic Therapeutic Announce Merger Trevena Inc Elevates Barry Shin to Executive VP and CFO GPCR Events, Meetings, and Webinars February 11 - 14, 2024 | 2024 BPS Annual Meeting February 20, 2024 | Career Opportunities in Pharmacology and Drug Discovery March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Fellowship- Mechanistic Biology NEW Research Scientist Post-Doc position Lead Researcher Senior Researcher in Structural Biology Post-Doctoral Fellow Join Dr. GPCR Ecosystem

Hello readers! Look at our curated GPCR coverage for this week, which includes 10 GPCR papers, seven industry news, and 2 GPCR events! This week's highlight: Congrats to Dr. Xavier Leroy on his appointment as CEO of GIO Therapeutics! Congratulations to Domain Therapeutics for being awarded the RHU SPRINT consortium grant. Erratum: In the past week's newsletter, the highlighted article should have read “Drs. Margarita Stampelou, Graham Ladds, and Antonios Kolocouris refine AlphaFold models using binding calculations for human adenosine A3 receptor. “ Dr. GPCR Symposia Our first upcoming symposium on March 15th this year is about GPCR activation and signaling. Confirmed speakers include Drs. Franziska Heydenreich, Sudarshan Rajagopal, Graham Ladds, and Michel Bouvier We will also have a poster session at each event on Zoom this year. Please email us at Hello@DrGPCR.com if you want to share your work with our community. Did you participate in our Symposia in 2023? Take 2 minutes to fill out this survey and let us know what you liked, what you didn’t, and what we can do better. Dr. GPCR University We're thrilled to share that all spots for the Applying Pharmacology to Drug Discovery course by Dr. GPCR University have been filled! Thank you for the overwhelming response. If you're still keen on joining this course but missed out on registration, don't worry; we've opened a waitlist. We appreciate your enthusiasm and interest in advancing your knowledge with us. We look forward to having you on board for future courses coming soon! Please fill out the waitlist form. We'll let you know if any spots become available. Dr. GPCR Volunteers Join our dynamic team as a volunteer! We’ll send your contributor articles to our community, keep you updated with GPCR papers, receive support and network with GPCR specialists at our events, and a free Premium Membership. Only 4 hours per month are required. If you are interested in applying, please email us your CV/Resume at  Hello@DrGPCR.com. Dr. GPCR Partnered Events 3rd GPCRs - Targeted Drug Discovery Summit  Join us at the 3rd GPCRs Targeted Drug Discovery Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10. Endocrine Metabolic GPCRs  Join the Endocrine Metabolic GPCRs event in Birmingham, UK, on April 22-23, 2024. Dr. GPCR members get a 5% discount with code GPCRDR5 until Feb 2nd, 2024. Let’s dive into the Classified GPCR News from January 22nd to 28th, 2024 GPCR Activation and Signaling Optical Control of Adenosine A2A Receptor Using Istradefylline Photosensitivity Comparative interactome analysis of α-arrestin families in human and Drosophila Functional diversification of cell signaling by GPCR localization GPCR Binders, Drugs, and more Decrypting orphan GPCR drug discovery via multitask learning GPCRs in Cardiology, Endocrinology, and Taste The Role of Gut Microbiota and Associated Compounds in Cardiovascular Health and its Therapeutic Implications The perspective of cAMP/cGMP signaling and cyclic nucleotide phosphodiesterases in aortic aneurysm and dissection GPCRs in Oncology and Immunology Molecular docking and dynamics simulation studies uncover the host-pathogen protein-protein interactions in Penaeus vannamei and Vibrio parahaemolyticus Involvement of Protease-Activated Receptor2 Pleckstrin Homology Binding Domain in Ovarian Cancer: Expression in Fallopian Tubes and Drug Design Structural and Molecular Insights into GPCR Function Optimizing cryo-EM structural analysis of Gi-coupling receptors via engineered Gt and Nb35 application Imaging GPCR Dimerization in Living Cells with Cucurbit[7]uril and Hemicyanine as a "Turn-On" Fluorescence Probe Industry News Domain Therapeutics awarded Hospital-University Research in Health (RHU) SPRINT consortium grant to progress its proprietary CCR8 antibody candidate to the clinic Novo strikes another obesity drug deal Sosei Heptares Webinar Presentation for FY2023 Financial Results Novartis Automates New Radioligand Therapy Production Plant Novartis’ Lutathera reduces disease progression risk in GEP-NET trial Novo Nordisk hits $500 billion in market value as it flags soaring demand for Wegovy, Ozempic Dr. Xavier Leroy appointed as CEO of GIO Therapeutics GPCR Events, Meetings, and Webinars NOW! February 1 | GPCR Forum ECI February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting NEW February 20, 2024 | Career Opportunities in Pharmacology and Drug Discovery March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Post-Doc position Lead Researcher Senior Researcher in Structural Biology Post-Doctoral Fellow Postdoctoral Fellow Research Laboratory Specialist Associate Join Dr. GPCR Ecosystem

Hello readers! Check out our curated GPCR coverage for this week, which includes 14 GPCR papers, four industry news, one GPCR Event, and two GPCR job ads! This week's highlight: Dr. Graham Ladds’ team refines AlphaFold models using binding calculations for human adenosine A3 receptor. Dr. GPCR University Our first Dr. GPCR University course, Applying Pharmacology to Drug Discovery, led by Dr. Terry Kenakin, starts February 8th, 2024. Due to popular demand, we have opened additional spots. If you'd like to join colleagues and Dr. Kenakin in a small group setting, hurry and register today. Only three spots remain. The course covers basic pharmacology in four weekly segments and is open to all with a free site membership. The cost is USD $299 and includes: Four live Zoom sessions (1 hour lecture + 30 mins Q&A each) A 30-minute one-on-one meeting with Dr. Kenakin Access to the cohort’s Dr. GPCR Ecosystem group Access to course materials and recordings A course completion certificate signed by Dr. Kenakin and Dr. GPCR Complimentary one-year Dr. GPCR Ecosystem Premium memberships (a $250 saving) Access to Dr. GPCR Ecosystem contents and perks Go to Dr. GPCR University and secure your spot before registration ends on February 1, 2024. Dr. GPCR Partnered Events March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit  We're partnering again with the 3rd GPCRs - Targeted Drug Discovery Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10 at checkout. Don't miss out! April 22 - 23, 2024 | Endocrine Metabolic GPCRs  Join Dr. GPCR at the Endocrine Metabolic GPCRs Summit on April 22-23, 2024, in Birmingham, UK. Dr. GPCR Ecosystem Members get a 5% discount with code GPCRDR5 at checkout until Feb 2nd, 2024. Hurry and don't miss out! Let’s dive into the Classified GPCR News from January 15th to 21st, 2024 Adhesion GPCRs The adhesion GPCR GPR116/ADGRF5 has a dual function in pancreatic islets regulating somatostatin release and islet development GPCR Activation and Signaling In Vitro Module Editing Of NRPS Enables Production Of Highly Potent Gq-Signaling Inhibitor FR900359 Derived From Unculturable Plant Symbiont Systematic assessment of chemokine ligand bias at the human chemokine receptor CXCR2 indicates G protein bias over β-arrestin recruitment and receptor internalization Class VI G protein-coupled receptors in Aspergillus oryzae regulate sclerotia formation through GTPase-activating activity A cholesterol switch controls phospholipid scrambling by G protein-coupled receptors Decoding anaphylatoxins: unveiling the molecular mechanisms of complement receptor activation and signaling GPCR Binders, Drugs, and more Computational Workflow for Refining AlphaFold Models in Drug Design Using Kinetic and Thermodynamic Binding Calculations: A Case Study for the Unresolved Inactive Human Adenosine A3 Receptor GPCRs in Cardiology, Endocrinology, and Taste Hepatic Regulator of G protein Signaling 14 Ameliorates NAFLD through Activating cAMP-AMPK Signaling by Targeting Giα1/3 APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease Hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation GPCRs in Oncology and Immunology The orphan G protein-coupled receptor 141 expressed in myeloid cells functions as an inflammation suppressor Methods & Updates in GPCR Research G-Protein Coupled Receptor Gpr-1 Is Important for the Growth and Nutritional Metabolism of an Invasive Bark Beetle Symbiont Fungi Leptographium procerum Editorial: Advanced biophysical and biochemical technologies to study GPCR signal transduction Structural and Molecular Insights into GPCR Function Segregation of nascent GPCRs in the ER-to-Golgi transport by CCHCR1 via direct interaction Industry News Novartis Lutathera® significantly reduced risk of disease progression or death by 72% as first-line treatment for patients with advanced gastroenteropancreatic neuroendocrine tumors Neurocrine Biosciences Announces Conference Call and Webcast of Fourth Quarter and Year-End 2023 Financial Results St. Jude Children’s Research Hospital adds $13 million project to Research Collaboratives Program AIRSUPRA® (albuterol/budesonide) now available as the first and only FDA-approved anti-inflammatory rescue option for asthma GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting NEW March 13 - 15 | 9th German Pharm-Tox Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Post-Doc position NEW Lead Researcher Senior Researcher in Structural Biology Post-Doctoral Fellow Postdoctoral Fellow Research Laboratory Specialist Associate Postdoctoral Scientist Principal Investigator, In Vitro Biology Join Dr. GPCR Ecosystem

Hi readers! Dive into our GPCR coverage for this week! We’ve curated 10 GPCR papers, seven industry news, and two GPCR job ads! This week's highlight: Dr. Kathleen M Caron and her team studied the GPER/GPR30 complex with β1-adrenergic receptor and AKAP5 in MCF7 breast cancer cells. Dr. GPCR University February 8 - 29: Join Dr. GPCR University's live course with Dr. Terry Kenakin. The course covers basic pharmacology in four weekly segments. Registrations are open to everyone (you will need to become a free site member) and end on February 1st, 2024! Hurry and secure your spot today! The cost is $299 and includes: All 4 live Zoom sessions ( 4x 1 hour lecture + 30 mins Q&A) 30-minute one-on-one meeting with Dr. Kenakin, according to his availability Access to the cohort’s Dr. GPCR Ecosystem group, where you can find Dr. Kenakin and your classmates Access to the course materials and recordings Course completion certificate signed by Dr. Kenakin and Dr. GPCR Complimentary one-year Dr. GPCR Ecosystem Premium memberships,  a $250 saving Access to Dr. GPCR Ecosystem contents and perks, including our forums, private groups, and all Ecosystem members Only 9 Spots Remain!! Go to Dr. GPCR University and save your spot today! Dr. GPCR Partnered Events March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit Exciting news! We're partnering again with the 3rd GPCRs - Targeted Drug Discovery Summit in Boston on March 5-7, 2024. Dr. GPCR Members get 10% off with code MPDRGPCR10 at checkout. Don't miss out! April 22 - 23, 2024 | Endocrine Metabolic GPCRs Join us at the Endocrine Metabolic GPCRs event on April 22-23, 2024 in Birmingham, UK. Dr. GPCR members get a 5% discount with code GPCRDR5 at checkout until Feb 2nd, 2024. Hurry and don't miss out! Let’s dive into the Classified GPCR News from January 8th to 14th, 2024 Adhesion GPCRs Conformational transitions and activation of the adhesion receptor CD97 GPCR Activation and Signaling Biased Signaling in Mutated Variants of β2-Adrenergic Receptor: Insights from Molecular Dynamics Simulations GPCRs in Cardiology, Endocrinology, and Taste Propionate functions as a feeding-state-dependent regulatory metabolite to counter pro-inflammatory signaling linked to nutrient load and obesity GPCRs in Neuroscience The Na+ leak channel NALCN controls spontaneous activity and mediates synaptic modulation by α2-adrenergic receptors in auditory neurons GPCRs in Oncology and Immunology G protein-coupled estrogen receptor (GPER)/GPR30 forms a complex with the β1-adrenergic receptor, a membrane-associated guanylate kinase (MAGUK) scaffold protein, and protein kinase A anchoring protein (AKAP) 5 in MCF7 breast cancer cells Reviews, GPCRs, and more The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases The progress of small molecules against cannabinoid 2 receptor (CB2R) Ketone bodies as chemical signals for the immune system AI-driven GPCR analysis, engineering, and targeting Structural and Molecular Insights into GPCR Function Characterizing conformational states in GPCR structures using machine learning Industry News Exscientia Unveils MolFlux: Empowering the ML Community in Molecular Predictive Modelling NanoImaging Services Appoints John Rigg as Chief Executive Officer Unraveling GPCRs Conformations: A Leap in Drug Discovery with STAGS Machine Learning Model Three GPCR Companies Earn Prestigious Best Places to Work Certification in 2023 Orion Biotechnology will be presenting at the OBIO 2024 Investment Summit X-rays to AlphaFold: the future structure of drug discovery Aelis Farma Achieves Milestone: Randomisation Concludes in Largest-Ever Phase 2b Clinical Trial for Cannabis Addiction Treatment AEF0117 GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Senior Researcher in Structural Biology NEW Post-Doctoral Fellow Postdoctoral Fellow Research Laboratory Specialist Associate Postdoctoral Scientist Principal Investigator, In Vitro Biology Associate Scientist Postdoctoral Scholar - O’Neill Lab Explore Dr. GPCR Ecosystem

Hello readers! The newest GPCR research is hot off the press! We’ve curated 18 GPCR papers, 8 industry news, and 2 GPCR job offers! This week's highlights: Congratulations to Drs. Inês Pinheiro and Oliver Hartley from the Orion Biotechnology team on their recent study on Arylsulfatases and neuraminidases! Congratulations to Domain Therapeutics for appointing Michael Gottlieb as Chairman and Dr. Anthony Johnson as President/CEO! Save the dates: February 8 - 29: Join Dr. GPCR University's live Zoom sessions hosted by Dr. Terry Kenakin. The course covers basic pharmacology in four weekly segments. Only ten spots remain. Registrations are open to everyone (you will need to become a free site member) and end on February 1st, 2024! Hurry and secure your spot today! The cost is $299 and includes: All 4 live Zoom sessions ( 4x 1 hour lecture + 30 mins Q&A) 30-minute one-on-one meeting with Dr. Kenakin, according to his availability Access to the cohort’s Dr. GPCR Ecosystem group, where you can find Dr. Kenakin and your classmates Access to the course materials and recordings Course completion certificate signed by Dr. Kenakin and Dr. GPCR Complimentary one-year Dr. GPCR Ecosystem Premium memberships, a $250 saving Access to Dr. GPCR Ecosystem contents and perks, including our forums, private groups, and all Ecosystem members Go to Dr. GPCR University and save your spot today! Let’s dive into the Classified GPCR News from January 1st to 7th, 2024. Adhesion GPCRs The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila Structure, ligands, and roles of GPR126/ADGRG6 in the development and diseases GPCR Activation and Signaling Proinflammatory chemokine CXCL14 activates MAS-related G protein-coupled receptor MRGPRX2 and its putative mouse ortholog MRGPRB2 Metabolite-sensing GPCRs in rheumatoid arthritis Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP Molecular mechanism of antihistamines recognition and regulation of the histamine H1 receptor [Enhancement of mast cells activation by ATP via P2X4 receptor] Osmotic stress studies of G-protein-coupled receptor rhodopsin activation GPCR Binders, Drugs, and more Chimeric antigens displaying GPR65 extracellular loops on a soluble scaffold enabled the discovery of antibodies, which recognized native receptor Targeting class A GPCRs for hard tissue regeneration GPCRs in Neuroscience Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor Methods & Updates in GPCR Research RediscMol: Benchmarking Molecular Generation Models in Biological Properties Characterization of the real-time internalization of nine GPCRs reveals distinct dependence on arrestins and G proteins A method for structure determination of GPCRs in various states Reviews, GPCRs, and more G Protein-coupled Receptors (GPCRs) as Potential Therapeutics for Psychiatric Disorders Structural and Molecular Insights into GPCR Function Apelin Receptor Dimerization and Oligomerization The role of leucine and isoleucine in tuning the hydropathy of class A GPCRs Arylsulfatases and neuraminidases modulate engagement of CCR5 by chemokines by removing key electrostatic interactions Industry News Domain Therapeutics strengthens leadership team to spearhead global development and North American expansion as the leading GPCR immuno-oncology company Sosei Group Announces Appointment of Experienced Pharmaceutical Executive Toshihiro Maeda as Chief Operating Officer Rhythm Pharmaceuticals and LG Chem Life Sciences Enter Agreement for Rhythm to Acquire Global Rights to Oral MC4R Agonist LB54640 Addex to Present at Biotech Showcase™ 2024 Establishing our first international translational research project - Institute for Protein Design Generate:Biomedicines Fortifies Leadership in Generative AI with Advancing Clinical Pipeline and Expanded Amgen Collaboration, Overviewed at the 42nd Annual J.P. Morgan Healthcare Conference Isomorphic Labs Announces Strategic Multi-Target Research Collaboration With Novartis Salipro Biotech announces multi-target research collaboration with an additional Top5 crop protection company GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Fellow NEW Research Laboratory Specialist Associate Postdoctoral Scientist Principal Investigator, In Vitro Biology Associate Scientist Postdoctoral Scholar - O’Neill Lab Junior Research Scientist Postdoctoral Fellow Explore Dr. GPCR Ecosystem

Warm greetings and a resounding welcome back to our GPCR Weekly Newsletter, rejuvenated after the festive season! We’ve curated 23 GPCR papers, four industry news, and 3 GPCR job posts! This week's highlight: Drs. Franziska M Heydenreich, Michel Bouvier, Brian Kobilka, M Madan Babu, and their team's work on Molecular determinants of ligand efficacy and potency in GPCR signaling Save the date: February 8 - 29: Join Dr. GPCR University's live Zoom sessions hosted by Dr. Terry Kenakin. The course covers basic pharmacology in four weekly segments. Only 12 out of 20 spots remain. Registrations are open to Dr. GPCR Ecosystem Members! The cost is $299 and includes: All 4 live Zoom sessions ( 4x 1 hour lecture + 30 mins Q&A) Complimentary one-year Dr. GPCR Ecosystem Premium memberships 30-minute one-on-one meeting with Dr. Kenakin, according to his availability Access to the cohort’s Dr. GPCR Ecosystem group, where you can find Dr. Kenakin and your classmates Access to the course materials and recordings once the course is completed Course completion certificate signed by Dr. Kenakin and Dr. GPCR Access to Dr. GPCR Ecosystem contents and perks, including our forums, private groups, and all Ecosystem members Go to Dr. GPCR University and save your spot today! Let’s dive into the Classified GPCR News from December 18th to 31st, 2023. Adhesion GPCRs Latrophilin, an adhesion GPCR with galactose-binding lectin domain involved in the innate immune response of Tribolium castaneum GPCR Activation and Signaling Palmitoylation of the Glucagon-like Peptide-1 Receptor Modulates Cholesterol Interactions at the Receptor-Lipid Microenvironment Basal interaction of the orphan receptor GPR101 with arrestins leads to constitutive internalization Identification of G Protein-Coupled Receptors (GPCRs) Associated with Lambda-Cyhalothrin Detoxification in Cydia pomonella Molecular determinants of ligand efficacy and potency in GPCR signaling Activation and characterization of G protein-coupled receptors for CHHs in the mud crab, Scylla paramamosain Reshaping the yeast galactose regulon via GPCR signaling cascade GPCR Binders, Drugs, and more Biased agonists of GPR84 and insights into biological control Larixol is not an inhibitor of Gαi containing G proteins and lacks effect on signaling mediated by human neutrophil expressed formyl peptide receptors GPCRs in Cardiology, Endocrinology, and Taste Beta cell primary cilia mediate somatostatin responsiveness via SSTR3 Inhibition of a novel Dickkopf-1-LDL receptor-related proteins 5 and 6 axis prevents diabetic cardiomyopathy in mice GPCRs in Neuroscience Coexistence within one cell of microvillous and ciliary phototransductions across M1- through M6-IpRGCs Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation Methods & Updates in GPCR Research Direct Binding Methods to Measure Receptor-Ligand Interactions How accurately can one predict drug binding modes using AlphaFold models? Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans Reviews, GPCRs, and more Classifying tetraspanins: A universal system for numbering residues and a proposal for naming structural motifs and subfamilies Comparative genomic analysis of chemosensory-related gene families in gastropods Unraveling the G protein-coupled receptor superfamily in aphids: Contractions and duplications linked to phloem feeding Structural and Molecular Insights into GPCR Function Studying allosteric regulation of chemokines and antagonists using a nanoscale hCCR3 receptor sensor GPCR-G protein selectivity revealed by structural pharmacology Industry News The Adrenaline Puzzle Solved: Scientists Untangle Key Cell Receptor's Inner Workings Sosei Heptares to Present at 42nd Annual J.P. Morgan Healthcare Conference Andrew Hopkins appointed CBE by HM King Charles III Voyager Therapeutics Enters Capsid License Agreement and Strategic Collaboration with Novartis to Advance Novel Gene Therapies GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Scientist NEW Principal Investigator, In Vitro Biology NEW Associate Scientist Postdoctoral Scholar - O’Neill Lab Junior Research Scientist Postdoctoral Fellow Post-Doc Research Associate Assistant/Associate Professor Explore Dr. GPCR Ecosystem

The chemokine receptor system is implicated in a wide range of inflammatory, autoimmune and infectious diseases (Proudfoot 2002), and in recent years attention has increasingly focused on cancer, where tumors hijack the chemokine system to provide growth and survival signals, establish and maintain an immunosuppressive tumor microenvironment, and facilitate metastatic spread (Nagarsheth, Wicha, and Zou 2017; Poeta et al. 2019). The involvement of chemokines and their receptors in several aspects of cancer biology, represents a potential target for immunotherapy, which is reflected on the amount of ongoing clinical trials (currently 26 ongoing, completed or recruiting) (Isberg et al. 2016). Different reviews have extensively described the success and failure in drug discovery on chemokine receptors (Poeta et al. 2019). The therapeutic approaches mainly include small molecule inhibitors, as well as monoclonal antibodies and antagonist peptide analogs. There are only two drugs in the market targeting chemokine receptors: maraviroc, an allosteric and reversible inhibitor of the CCR5 used in HIV therapy; and the small molecule plerixafor, a CXCR4 antagonist used in cancer therapy (Isberg et al. 2016). The anti-CCR4 antibody mogamulizumab has also been approved in Japan and by the FDA for the treatment of mycosis fungoides or Sézary syndrome in adults which are subtypes of cutaneous T-cell lymphoma (CTCL) (Lewis and Rook 2020). A lot of effort has been put forward to target CKRs especially in cancer, nevertheless, targeting this system is a challenging task due to its complexity and redundancy. Redundancy can be exemplified by the tumor infiltration of Treg cells which can be driven directly by different receptors (CCR4, CCR5, CCR6, CCR7, and CXCR3) and so inhibition of this process through blockade of a single receptor is hampered (O'Hayre et al. 2010). At a molecular level, different ligands bind to the same receptor and vice-versa (Marcuzzi et al. 2018). This redundancy can be seen as problematic in drug discovery as blocking a single receptor might not produce clinical efficacy. Therefore, an alternative approach is to make use of chemokine receptors redundancy and the fact that different chemokine receptors are overexpressed and promote cancer progression, and use promiscuous non-peptide antagonists able to target more than one chemokine receptor subtype, the concept of polypharmacology (Horuk 2009). On the other hand, Shall and Proudfoot excluded the idea of molecular redundancy, pointing out that, in some cases, inappropriate target selection and insufficient dosing of chemokine receptor antagonists in vivo might be the main hurdle (Schall and Proudfoot 2011). Subsequent reports characterizing small molecule agonists for CXCR3 further substantiated the notion that redundancy is not a feature of the chemokine system (Nedjai et al. 2012), but more research in different cellular contexts is needed to fully address this question. Another important aspect in CKRs targeted drug discovery is the concept of biased agonism/antagonism, also known as functional selectivity. Drug discovery is shifting towards the development of biased ligands, which promote the engagement of the receptor with a certain effector, thus enriching a specific signaling pathway (Smith, Lefkowitz, and Rajagopal 2018). In the chemokine-receptor system, different chemokines are able to activate different pathways, which can also vary depending on the cell and tissue context. Signaling bias can be seen as complex as advantageous since selectively inhibiting certain signaling pathways while sparing others, can prevent some of the negative off-target effects. An example is CCL5 which binds to CCR1, CCR3 and CCR5, and induces different patterns of receptor recycling where CCR5 recycles back to the cell surface (Mack et al. 1998), CCR3 is partially restored to the cell surface and partially targeted to lysosomes (Zimmermann, Conkright, and Rothenberg 1999) and CCR1 does not recycle (Elsner et al. 2001). Furthermore, both chemokines and receptors can homo- and hetero-oligomerize, impacting receptor/ligand-binding and signaling patterns, by modulating ligand binding, as well as G-protein coupling or interaction with other signaling molecules (Sohy et al. 2009; Wang and Norcross 2008). Therefore, the in vivo state of the receptor and its existence as homo and herero-oligomeres at the cell surface should be considered when assessing the pharmacological profile of new compounds. Moreover, it is difficult to demonstrate clinical efficacy with a specific antagonist to a single receptor as patients cannot be stratified into CKRs specific subpopulations for a specific disease (Horuk 2009). Further difficulties arise from the existence of cross-reactivity with other GPCRs and differences in the chemokine systems between species which, in some cases, hampers the pre-clinical development (Marcuzzi et al. 2018). In fact, the requirements in terms of safety margin, oral bioavailability, and frequency of administration are particularly rigorous for this class, as the majority of potential therapeutic applications are situated in the area of chronic inflammatory disease (Proudfoot, Power, and Schwarz 2010). An additional milestone is represented by the large binding pocket of chemokine receptors which are regulated by globular protein ligands, unlike most of the class A GPCRs ligands that are small molecules or short peptides. These larger interfaces represent the typical protein-protein interactions which are difficult to modulate using small molecules (Sohy et al. 2009; Wang and Norcross 2008); and are also too small to be engaged by antibodies, which can only interact with the extracellular domain of the receptor ((Zimmermann, Conkright, and Rothenberg 1999). A promising strategy corresponds to the use of engineered chemokine analogs which are analogs of the natural ligands, allowing a better molecular fit with the binding pocket (Paolini-Bertrand et al. 2018). Overall, the future potential lies in using different therapeutic modalities to modulate the stromal component, overcome chemotherapy resistance, and optimize immune responses and a comprehensive understanding of the role of the chemokine receptor system in different malignancies is crucial to avoid potential side effects and enhance the efficacy of immunotherapeutic strategies.

Hi friends! The latest and greatest in GPCR research is here, this week we’ve curated 14 GPCR papers, 7 industry news, and 2 GPCR job offers! This week's highlights: Kudos to our partner, GPCR Therapeutics, for partnering with Bridge Biotherapeutics to pioneer IPF treatment with CXCR4-LPA1 inhibitors! Dr. Ross Cheloha's research involves semi-synthetic nanobody-ligand conjugates with enhanced transcriptional outputs at neurokinin receptor-1 Congratulations to Dr. Nicole Perry-Hauser, on her selection as a 2024 Discovery Science Emerging Scholar at Vanderbilt University! Save the date: February 8 - 29: Join Dr. GPCR University's live Zoom sessions hosted by Dr. Terry Kenakin. The course covers basic pharmacology in four weekly segments. Only 14 out of 20 spots remain. Registrations are open to Dr. GPCR Ecosystem Premium Members and free site Members! The cost is $299 and includes: All 4 live Zoom sessions ( 4x 1 hour lecture + 30 mins Q&A) Complementary one-year Dr. GPCR Ecosystem Premium memberships 30-minute one-on-one meeting with Dr. Kenakin, according to his availability Access to the cohort’s Dr. GPCR Ecosystem group, where you can find Dr. Kenakin and your classmates Access to the course materials and recordings once the course is completed Course completion certificate signed by Dr. Kenakin and Dr. GPCR Access to Dr. GPCR Ecosystem contents and perks, including our forums, private groups, and all Ecosystem members Go to Dr. GPCR University and save your spot today! The GPCR Weekly News will take a holiday break. We'll pause our regular updates during this time and will resume our newsletter in the upcoming year on Thursday, January 4, 2024. We appreciate your continued support and readership. Wishing you all a joyful holiday season and a prosperous New Year!🎄✨ Let’s dive into the Classified GPCR News from December 11th to 17th, 2023. GPCR Activation and Signaling GPCR screening reveals that the metabolite receptor HCAR3 regulates epithelial proliferation, migration, and cellular respiration Spatiotemporal Optical Control of Gαq-PLCβ Interactions Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism GPCR Binders, Drugs, and more Semi-synthetic nanobody-ligand conjugates exhibit tunable signaling properties and enhanced transcriptional outputs at neurokinin receptor-1 GPCRs in Cardiology, Endocrinology, and Taste Transcriptional profiling of Kiss1 neurons from arcuate and rostral periventricular hypothalamic regions in female mice Cardiac optogenetics: shining light on signaling pathways GPCRs in Oncology and Immunology Leukotriene B4 receptor 2 governs macrophage migration during tissue inflammation From odor to oncology: non-canonical odorant receptors in cancer Methods & Updates in GPCR Research Phosphorylation Sites of the Gastric Inhibitory Polypeptide Receptor (GIPR) Revealed by Trapped-Ion-Mobility Spectrometry Coupled to Time-of-Flight Mass Spectrometry (TIMS-TOF MS) A rapid, tag-free way to purify functional GPCRs tANCHOR fast and cost-effective cell-based immunization approach with focus on the receptor-binding domain of SARS-CoV-2 Microscopy and spectroscopy approaches to study GPCR structure and function Structural and Molecular Insights into GPCR Function Using AlphaFold and Experimental Structures for the Prediction of the Structure and Binding Affinities of GPCR Complexes via Induced Fit Docking and Free Energy Perturbation A computational insight on the aromatic amino acids conjugation with [Cp*Rh(H2O)3]2+ by using the meta-dynamics/FMO3 approach Industry News GPCR Therapeutics Announces Out-Licensing Agreement with Bridge Biotherapeutics in Idiopathic Pulmonary Fibrosis Former execs from Pfizer obesity drug program have started a new biotech with $52M from VC fund ATP Structure Therapeutics - Providing the next generation of high-impact medicines Structure Therapeutics Provides Comprehensive GSBR-1290 Program Update Including Clinically Meaningful Proof-of-Concept Data From Phase 2a Clinical Study Neurocrine opening two Phase 1 trials in oral Parkinson’s therapies Bearing Fruit: Deep Apple Therapeutics Launches to Screen AI-Generated Virtual Libraries AbbVie to Acquire Cerevel Therapeutics in Transformative Transaction to Strengthen Neuroscience Pipeline GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Scholar - O’Neill Lab NEW Junior Research Scientist Postdoctoral Fellow Post-Doc Research Associate Assistant/Associate Professor Principal scientist – oncology biomarker expert Postdoctoral Fellow Scientific Assistant Explore Dr. GPCR Ecosystem

Hi GPCR lovers! We have some exciting news, this week we’ve curated 13 GPCR papers, 4 industry news, and 3  job opportunities! This week's highlight: Dr. Bryan L Roth study on Illuminating the understudied GPCR-ome Save the dates: February 8 - 29: Dr. GPCR University live Zoom sessions hosted by Dr. Terry Kenakin. This comprehensive course covers fundamental pharmacology in four weekly segments, delving into Agonists, Antagonists, and Allosteric Modulators.  Registrations open on December 15th and close on February 1st to both Dr. GPCR Ecosystem members and non-members, with limited spots available for 20 attendees at USD 299. The package includes four live Zoom sessions, a one-year Dr. GPCR Ecosystem Premium membership, a personal meeting opportunity with Dr. Kenakin, access to a dedicated group, course materials, recordings, and a completion certificate endorsed by Dr. Kenakin and Dr. GPCR. For more information click HERE, don’t miss out on this exclusive opportunity! Now check out the weekly Classified GPCR News from December 4th to 10th, 2023. GPCR Activation and Signaling Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers Structural basis of G protein-Coupled receptor CMKLR1 activation and signaling induced by a chemerin-derived agonist Functional profiling of the G protein-coupled receptor C3aR1 reveals ligand-mediated biased agonism GPCR Binders, Drugs, and more Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor GPCRs in Neuroscience Research progress on the role of orphan receptor GPR139 in neuropsychiatric behaviours Rhodopsin orphan GPCR20 interacts with neuropeptides and directs growth, sexual differentiation, and egg production in female Schistosoma mansoni A Novel Flp Reporter Mouse Shows That TRPA1 Expression Is Largely Limited to Sensory Neuron Subsets Orphan peptide and G protein-coupled receptor signalling in alcohol use disorder GPCRs in Oncology and Immunology Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice Methods & Updates in GPCR Research Transcriptome analysis of Schizothorax oconnori (Cypriniformes: Cyprinidae) oocytes: The role of K+ in promoting yolk globule fusion and regulating oocyte maturation 19F-NMR studies of the impact of different detergents and nanodiscs on the A2A adenosine receptor Reviews, GPCRs, and more Structure, function and drug discovery of GPCR signaling Illuminating the understudied GPCR-ome Industry News Sosei Heptares’ Partner Neurocrine Biosciences Confirms its Plans to Evaluate Two New Muscarinic Agonist Candidates in Phase 1 Clinical Studies AbbVie to acquire neuroscience drugmaker Cerevel Therapeutics for $8.7 billion FDA approves two gene therapies for sickle cell disease, including first that uses CRISPR Pier Vincenzo Piazza, CEO of AELIS FARMA, Honored with Merit Medal by Nouvelle-Aquitaine Region Governor GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2024 | 2024 BPS Annual Meeting March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks June 25 - 29, 2024 | FENS Forum 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 Fellow NEW Post-Doc Research Associate NEW Assistant/Associate Professor Principal scientist – oncology biomarker expert Postdoctoral Fellow Scientific Assistant Scientist Lead Researcher Explore Dr. GPCR Ecosystem

Good day readers! This week we’ve curated 20 GPCR papers, 3 new events, 9 industry news, and 3 job opportunities! Discover our comprehensive coverage of GPCRs, We welcome GPCR paper suggestions! Submit your publications to Hello@DrGPCR.com for consideration. This week's highlight: Dr. Matthew T Eddy and his team's research on A2A adenosine receptor activation by G protein and mutations. Are you looking to hire? Or maybe looking for your next opportunity? Our Chief Matchmaker, Mark Schmeizl, is here to assist you. Simply complete this form to get in touch with him. November Dr. GPCR Newsletter is out now. Subscribe for this month's video featuring Dr. Alix Rouault. Ensure to catch the upcoming episodes of Dr. GPCR Podcast featuring Dr. Neil Grimsey and Dr. Katarzyna Marcinkiewicz. Be sure to look at the Classified GPCR News from November 27th to December 3rd, 2023. GPCR Activation and Signaling DANGER Signals Activate G -Protein Receptor Kinases Suppressing Neutrophil Function and Predisposing to Infection After Tissue Trauma Single-molecule visualization of human A2A adenosine receptor activation by a G protein and constitutively activating mutations Distinct activation mechanisms of β-arrestin-1 revealed by 19F NMR spectroscopy Role of protease activated receptor 4 (PAR4) in mouse models of acute and chronic kidney injury GPCR Binders, Drugs, and more High-throughput virtual screening of potential inhibitors of GPR52 using docking and biased sampling method for Huntington's disease therapy Rational design of highly stabilized and selective adrenomedullin analogs Novel multi-target ligands of dopamine and serotonin receptors for the treatment of schizophrenia based on indazole and piperazine scaffolds-synthesis, biological activity, and structural evaluation Flavonoids as G Protein-coupled Receptors Ligands: New Potential Therapeutic Natural Drugs GPCRs in Cardiology, Endocrinology, and Taste Phenylacetyl glutamine (PAGln) enhances cardiomyocyte death after myocardial infarction through β1 adrenergic receptor Comparative transcriptomic analysis of mammary gland tissues reveals the critical role of GPR110 in palmitic acid-stimulated milk protein and fat synthesis GPCRs in Neuroscience Targeting sensory neuron GPCRs for peripheral neuropathic pain GPCRs in Oncology and Immunology Expression prevalence and dynamics of GPCR somatostatin receptors 2 and 3 as cancer biomarkers beyond NET: a paired immunohistochemistry approach The combination of brentuximab vedotin and chidamide synergistically suppresses the proliferation of T-cell lymphoma cells through the enhancement of apoptosis Methods & Updates in GPCR Research Modulating signalling lifetime to optimise a prototypical animal opsin for optogenetic applications Imaging flow cytometry of tumoroids: A new method for studying GPCR expression GPCR molecular dynamics forecasting using recurrent neural networks A method for multiple-sequence-alignment-free protein structure prediction using a protein language model Reviews, GPCRs, and more Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review) Structural and Molecular Insights into GPCR Function Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors Industry News Sosei Heptares to take back GPCR agonist after GSK changes course All-rounder among receptors inspires drug research Tectonic Therapeutic Announces Start of First Clinical Program for GPCR-Targeted Biologic Trevena Announces Acceptance of Abstract Examining the Use of OLINVYK in Patients with Acute Burn Injuries Carmot Therapeutics Enters into Definitive Merger Agreement with Roche New Clinical Trial Explores Novel Target In Parkinson’s Treatment GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition February 11 - 14, 2023 | 2024 BPS Annual Meeting March 5 - 7, 2024 | 3rd GPCRs - Targeted Drug Discovery Summit March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 4 - 7, 2024 | American Physiology Summit April 5 - 10, 2024 | AACR Annual Meeting April 22 - 23, 2024 | Endocrine Metabolic GPCRs May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 7, 2024 | Chemotactic Cytokines NEW June 9 - 14, 2024 | 2024 Phosphorylation and G-Protein Mediated Signaling Networks NEW June 25 - 29, 2024 | FENS Forum 2024 October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry NEW October 23 - 25, 2024 | 11th Adhesion GPCR Workshop July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs NEW Principal scientist – oncology biomarker expert NEW Postdoctoral Fellow NEW Scientific Assistant Scientist Lead Researcher Post-Doctoral Fellow Sr Scientist in Obesity, Muscle, and Metabolism Post-Doctoral Fellow Explore Dr. GPCR Ecosystem