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Thank you for your interest in the Applying Pharmacology to Drug Discovery course with Dr. GPCR University. All spots in the course are now filled. To join our waitlist please fill out this form - https://forms.gle/xPZjX56LkEvhGv6b6 We'll let you know if any spots become available. Thank you for your understanding and enthusiasm! ----------------------------------------------------------------------------------------------------- The main objective of this course is to give the registrant a good overall understanding of the unique science of pharmacology and how it can describe drug action in system-independent ways. This allows predictions of drug activity in all physiological systems, not only the system where testing is done. Techniques will be described to quantify drug activity in terms of affinity, efficacy, and allosteric function. Pharmacology is a unique discipline and is critical to drug discovery. Registrants will learn: 1. Methods to characterize the 3 major drug types. 2. What makes each drug type unique to therapeutic pharmacology? 3. Essential information needed to characterize the profile of a drug aimed at therapy. Modules: Week 1 - Fundamentals of Pharmacology Week 2 - Characterizing Agonists Week 3 - Characterizing Antagonists Week 4 - Characterizing Allosteric Modulators Registrations start on December 15th and close on February 2nd. Classes will be live from Zoom on Thursdays from 10 am to 11:30 am EST. Sessions will include a 1-hour live lecture plus 30 minutes of Q&A. Every participant will also get the chance to have a 1:1 meeting with Dr. Kenakin during the 4 weeks, scheduled according to the professor's availability. Participants who complete the course will get an online certification signed by the professor and the Dr.GPCR Team. A splendid time is guaranteed for all.

Dr. Kiyan Afzali   ‘What we observe is not nature itself, but nature exposed to our method of questioning.’ –Werner Heisenberg 1. Introduction Life scientists dedicate enormous resources towards meticulously understanding and implementing the biological frameworks of the world for the ultimate benefit of living beings. This pursuit in the best cases has remarkably led to groundbreaking technological advancements, such as life-saving medical treatments. However, the process is often fraught with deficits in accuracy and efficiency, leaving considerable space for improvement. Drug discovery is an extremely costly, lengthy, and risky venture [1-4] that requires $1–2 billion [5-8] invested over 10–15 years [5, 9, 10] with only a 7% chance of approval for candidates entering clinical trials [11-13]. This low success rate is due to inadequacies primarily in efficacy and secondarily in safety [5, 11], highlighting the limited translational capacity of preclinical studies. A reproducibility crisis exists where 47% of researchers have failed to replicate a published study that was originally conducted by another team and 23% have failed to do so for a study of their own [14]. An important reason for this unfavourable situation is that laboratory experiments are performed under highly controlled, abstract, and specific conditions, while complex biological phenomena are profoundly dependent on the context of a multitude of interactions [15]. The most diverse and common molecular target of drug medicines is G protein-coupled receptors (GPCRs) [16], which are interrogated through bioassays as the pharmacologist’s ‘eyes to see’ [17]. As researchers of these prime targets, it is our duty to routinely clean our lens of misleading artefacts and focus our efforts towards the most physiologically relevant observations. A pivotal concept for accurately interpreting the behaviour of GPCRs is their dependence on allostery. Allostery is a vital biochemical mechanism that has been described as ‘the second secret of life’, preceded only by the existence of the genome [18-20]. This process is a binding event that facilitates a change in the shape of a macromolecule which impacts a particular interaction at another region [21-24]. The behaviour occurs through a remodelling of the free energy landscape between thermodynamically coupled networks of amino acids from perturbations such as ligand binding, post-translational modification, or protein interactions, allowing proteins to sense and respond to changes in their environment [18, 20, 22, 23, 25]. GPCRs are considered nature’s ‘prototypical allosteric protein’ [21, 26, 27] because they are regulated in this fashion by ions, small molecules, lipids, receptor-activity modifying proteins, autoantibodies, membrane stretch, and even other GPCRs through dimerisation [28-30]. Rather than being static structures, GPCRs exist in an ensemble of different conformations that are interchangeable according to the free energy of the system [26, 27, 31]. Ligands binding to GPCRs can stabilise a distinct set of conformations, which promotes a certain pattern of interaction with various transducer proteins, leading to biased signalling [32]. Bioassays for interrogating GPCR structure and function typically rely on protein tags or modifications [33]. Tags are often peptides or entire proteins that are genetically engineered to be fused to a target protein to facilitate detection, purification, localisation, or characterisation of activity [34, 35]. Given the sensitive allosteric nature of GPCRs with their binding partners, tags or modifications are likely to influence their conformational dynamics and confound analyses of their properties. This notion has become more heavily supported by two recent studies that explored the ramifications of modifying the GPCR ternary complex on signalling [36, 37].   2. Receptor Modification Impacts Signalling Direct modifications of GPCRs can impact their G protein coupling propensities. For the serotonin 5-HT2A receptor (5-HT2AR) with the Gαi/o family of transducers, Wright and colleagues [36] demonstrated that an N-terminal 3x hemagglutinin tag narrowed activation from all subtypes except Gαi1 to only Gαz (Figure 1). Although the tag was found to decrease 5-HT2AR density, this impact on G protein coupling was primarily attributed to differences in the conformational dynamics of the receptor rather than a lowered sensitivity for detecting weaker interactions, as increasing receptor transfection only enhanced activation of GαoB and Gαz. These findings suggest that this tag, and potentially others, could have impacted the results of previous studies determining the 5-HT2AR structure, its molecular interactions with various ligands and canonical Gαq transducer, and conformational changes involved in active-state transitions [38]. This limited detection and modelling of 5-HT2AR-Gαi/o coupling could mistakenly divert attention from a potentially important pathway that has already shown relevance in the pathophysiology of schizophrenia and mechanism of psychedelic drugs [39-41]. The authors recommend that results obtained using a tagged receptor should be confirmed with an untagged version, and that whether identified coupling signatures have physiological relevance be further assessed in more appropriate biological systems [36].   Figure 1. Modifying the serotonin 5-HT2A receptor (5-HT2AR) with a 3x hemagglutinin (HA) tag as used in structural studies narrowed the activation of Gαi/o protein subtypes from all except Gαi1 to only Gαz in a recent study by Wright and colleagues [36].      3. G Protein Modification Influences Signalling Similar to GPCRs, modification of G proteins can influence transducer coupling signatures. A standard format of GPCR biosensors incorporates a luminescent tag on the G protein Gα subunit and Gβγ dimer, such that GPCR activation results in dissociation of these proteins and a decrease in signal [42, 43]. Wright and colleagues [36] showed that these heterotrimer-based biosensors for the 5-HT7A/B receptors (5-HT7A/BRs) were only able to detect interaction with the strongest coupling partner Gαs (Figure 2A), and for the glucagon-like-peptide-1 receptor (GLP-1R) even reported unproductive interactions involving conformational rearrangements of the Gαβγ protein without signalling. In contrast, biosensors of a strategically different format measuring unmodified active Gα subunits through G protein effector translocation to the plasma membrane captured additional weaker couplings with Gαi/o/z and Gαq/11/14/15 for the 5-HT7A/BRs (Figure 2A), and was immune to such irrelevant signals for the GLP-1R. Moreover, these alternate biosensors reported different Gαi/o coupling rankings between four of six subtypes for the 5-HT2AR, with the exceptions being the strongest and weakest interactions to Gαz and Gαi1, respectively (Figure 2B), as well as different coupling preferences between specific Gβγ pairs for the muscarinic acetylcholine M3 receptor (M3R) (Figure 2C). These findings suggest that GPCR biosensors consisting of modified G proteins, which have been implemented in pharmacological research and development for decades, may not be suitable for detecting and accurately evaluating the complete range of coupling interactions. The authors emphasise the importance of understanding the advantages and limitations of different assay technologies and taking these factors into consideration when interpreting results and drawing conclusions from studies [36].     Figure 2. Modifying G proteins with luminescent tags as used in biosensors altered the G protein coupling profiles of the (A) serotonin 5-HT7A/B receptors (5-HT7A/BRs) (subtypes activated are coloured in green and otherwise red), (B) serotonin 5-HT2A receptor (5-HT2AR), and (C) muscarinic acetylcholine M3 receptor (M3R) in a recent study by Wright and colleagues [36]. R luc: Renilla  luciferase, GFP: Green Fluorescent Protein. Another format of biosensors involves the use of mini-G proteins, which are genetically engineered portions of Gα subunits designed to stabilise GPCRs in their active conformations [44-46]. Unlike native Gα subunits, mini-G proteins do not bind Gβγ dimers or participate in nucleotide exchange [45, 46]. Manchanda and colleagues [37] showed that for the glucagon-like-peptide-1 receptor (GLP-1R), mini-Gs blocked β-arrestin recruitment, receptor internalisation, and endosomal trafficking, while other mini-G protein subtypes produced weaker or no such inhibition in correlation with their coupling selectivity. Similar effects of varying intensity were observed for several other GPCRs, including the β2-adrenergic receptor (β2-AR), μ-opioid receptor (MOR), free fatty acid receptor 2 (FFA2R), and glucose-dependent insulinotropic polypeptide receptor (GIPR) (Figure 3). Conversely, internalisation in the presence of mini-G proteins was maintained for a non-GPCR, the epidermal growth factor receptor (EGFR), which is instead a receptor tyrosine kinase. In contrast with mini-G proteins, the use of a nanobody, Nb37, previously developed to bind Gαs in complex with active GPCRs, enabled detection of GLP-1R activation both from the plasma membrane and endosomes. These findings suggest that the use of mini-G proteins could have hindered the accurate quantification of GPCR signalling from subcellular compartments in previous studies [44, 47-49]. Additionally, as mini-G proteins are increasingly implemented in structural determinations of GPCRs and fused with fluorescent or luminescent tags for evaluating signalling particular to various G protein subtypes, it is possible that they could influence the results of these studies with unexpected effects as well [50-52]. To circumvent their identified problem, the authors recommend checking GPCR internalisation rates to determine tolerable expression levels of mini-G proteins and validating results with other tools, such as those involving full-length G protein constructs [37].   Figure 3. Mini-G proteins as modified versions of Gα proteins inhibited β-arrestin recruitment, receptor internalisation, and endosomal trafficking for the glucagon-like-peptide-1 receptor (GLP-1R), β2-adrenergic receptor (β2-AR), µ-opioid receptor (MOR), free fatty acid receptor 2 (FFA2R), and glucose-dependent insulinotropic polypeptide receptor (GIPR) in a recent study by Manchanda and colleagues [37].   3. Conclusion and Outlook Overall, these latest studies demonstrate that modifying GPCRs or their binding partners for bioassays can alter their interactions and produce misleading results. This conundrum for the pharmacologist is analogous to the physicist’s [53] or social scientist’s [54-56] observer’s paradox, where determinations of quantum mechanical systems or human behaviour, respectively, are influenced by the act of observation [57]. Fortunately, GPCR researchers have solutions at their disposal to overcome this challenge, essentially in which, the allosteric nature of GPCRs must be respected. Moving forward, implementing and developing assay technologies that strategically operate using unmodified versions of these proteins and their binding partners will be important for ensuring that findings accurately reflect native biological processes and preclinical research can more reliably translate into therapeutic success.   References 1.            Freeman BB, 3rd, Yang L, Rankovic Z. Practical approaches to evaluating and optimizing brain exposure in early drug discovery. Eur J Med Chem. 2019;182:111643. 2.            Wager TT, Hou X, Verhoest PR, Villalobos A. Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties. ACS Chem Neurosci. 2010;1(6):435-49. 3.            Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004;3(8):711-5. 4.            Butlen-Ducuing F, Pétavy F, Guizzaro L, Zienowicz M, Salmonson T, Haas M, et al. Challenges in drug development for central nervous system disorders: a European Medicines Agency perspective. Nature Reviews Drug Discovery. 2016;15(12):813-814. 5.            Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it? Acta Pharmaceutica Sinica B. 2022;12(7):3049-3062. 6.            Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. Jama. 2020;323(9):844-853. 7.            DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: New estimates of R&D costs. J Health Econ. 2016;47:20-33. 8.            Schlander M, Hernandez-Villafuerte K, Cheng CY, Mestre-Ferrandiz J, Baumann M. How Much Does It Cost to Research and Develop a New Drug? 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Seven transmembrane receptors as nature's prototype allosteric protein: de-emphasizing the geography of binding. Mol Pharmacol. 2008;74(3):541-3. 27.         Kenakin TP. Biased signalling and allosteric machines: new vistas and challenges for drug discovery. Br J Pharmacol. 2012;165(6):1659-1669. 28.         Shen S, Zhao C, Wu C, Sun S, Li Z, Yan W, et al. Allosteric modulation of G protein-coupled receptor signaling. Frontiers in Endocrinology. 2023;14. 29.         Slosky LM, Caron MG, Barak LS. Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery. Trends in Pharmacological Sciences. 30.         van der Westhuizen ET, Valant C, Sexton PM, Christopoulos A. Endogenous allosteric modulators of G protein-coupled receptors. J Pharmacol Exp Ther. 2015;353(2):246-60. 31.         Kenakin T. The mass action equation in pharmacology. Br J Clin Pharmacol. 2016;81(1):41-51. 32.         Kenakin T. Biased Receptor Signaling in Drug Discovery. 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Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling. Science signaling. 2024;17(843):eabq7038. 38.         Kim K, Che T, Panova O, DiBerto JF, Lyu J, Krumm BE, et al. Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor. Cell. 2020;182(6):1574-1588.e19. 39.         García-Bea A, Miranda-Azpiazu P, Muguruza C, Marmolejo-Martinez-Artesero S, Diez-Alarcia R, Gabilondo AM, et al. Serotonin 5-HT2A receptor expression and functionality in postmortem frontal cortex of subjects with schizophrenia: Selective biased agonism via Gαi1-proteins. Eur Neuropsychopharmacol. 2019;29(12):1453-1463. 40.         González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, et al. Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior. Neuron. 2007;53(3):439-52. 41.         Muneta-Arrate I, Diez-Alarcia R, Horrillo I, Meana JJ. 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Engineering a minimal G protein to facilitate crystallisation of G protein-coupled receptors in their active conformation. Protein Eng Des Sel. 2016;29(12):583-594. 47.         Crilly SE, Ko W, Weinberg ZY,Puthenveedu MA. Conformational specificity of opioid receptors is determined by subcellular location irrespective of agonist. Elife. 2021;10. 48.         Truong ME, Bilekova S, Choksi SP, Li W, Bugaj LJ, Xu K, et al. Vertebrate cells differentially interpret ciliary and extraciliary cAMP. Cell. 2021;184(11):2911-2926.e18. 49.         Jimenez-Vargas NN, Gong J, Wisdom MJ, Jensen DD, Latorre R, Hegron A, et al. Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain. Proc Natl Acad Sci U S A. 2020;117(26):15281-15292. 50.         García-Nafría J, Tate CG. Cryo-EM structures of GPCRs coupled to Gs, Gi and Go. 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Ho, ho, ho, GPCR elves! As the year wraps up, we're thrilled to present the final edition of the GPCR Weekly Newsletter for 2024! As researchers, we all understand the importance of data in driving meaningful discoveries  and advancing our experiments.   At Dr. GPCR, we believe the same principle applies to building a better experience  for our online community.   We’d love to hear your thoughts on our website and its features  so that we can continue to support your work and foster collaborations in the GPCR field.   Your feedback  will guide us in tailoring resources , tools , and content to meet your needs better and help fuel your research. Thank you for sharing your perspective and helping us shape the future of the Dr. GPCR ecosystem! Best, Yamina & the Dr. GPCR Team This Week’s Highlights: Congratulations to Andrew Tobin for an incredible week filled with prestigious events, including receiving the British Pharmacological Society Vane Medal and switching on the Christmas lights at the University of Glasgow Advanced Research Centre! Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain Luke A Pattison , Rebecca H Rickman , Graham Ladds , Ewan St John Smith , et al. Attention, everyone! This is your last chance before the curtain closes: Classified GPCR News will be accessible only to VIP members next year! Indeed, all the details below will be limited to Premium Members . Don't miss out—upgrade now to keep up with your GPCR updates! Classified GPCR News  Let’s dive into the   Classified GPCR News from December 9th to 15th, 2024 Industry News When science meets serendipity: How accidental discoveries could revolutionise women’s health Seven unanswered questions about blockbuster weight-loss drugs Transforming Drug Discovery: Insights from Viva Biotech's GPCR and TPD Structural Biology Platforms GPCR Events, Meetings, and Webinars December 10 - 12, 2024 | Pharmacology 2024 January 13 - 16, 2025 | PepTalk 2025 January 25 - 29, 2025 | SLAS 2025 February 15 - 16, 2025 | Structural and Functional Approaches in GPCR Drug Discovery February 15 - 19, 2025 | BPS 2025 February 16 - 21, 2025 | Harnessing the Power of Advanced Multimodal Approaches to GPCR Drug Discovery March 12 - 14, 2025 | NextGen Biomed 2025 March 25 - 28, 2025 | 10th German Pharm-Tox Summit April 1 - 5, 2025 | XXIII GEM Meeting in 2025 April 3 - 6, 2025 | ASPET 2025 April 14 - 17, 2025 | 20th Drug Discovery Chemistry April 24 - 27, 2025 | American Physiology Summit 2025 April 25 - 30, 2025 | AACR Annual Meeting 2025 May 12 - 15, 2025 | PEGS 2025 May 20 - 22, 2025 | SLAS Europe 2025 June 16 - 19, 2025 | BIO International Convention 2025 July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs GPCR Molecular Pharmacologist Scientist - Biology Scientist I Cell Biology - Tectonic Therapeutic Senior Principal Scientist, Medicinal Chemistry PhD fellowship in GPCR mechanosensing Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist GPCR Activation and Signaling Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain Regulation of the chemokine receptors CXCR4 and ACKR3 by receptor activity-modifying proteins Single-cell transcriptomics of vomeronasal neuroepithelium reveals a differential endoplasmic reticulum environment amongst neuronal subtypes Methods & Updates in GPCR Research High-throughput optimisation of protein secretion in yeast via an engineered biosensor Optimized vector for functional expression of the human bitter taste receptor TAS2R14 in HEK293 cells Reviews, GPCRs, and more The role of the endocannabinoid system in the pathogenesis and treatment of epilepsy Become a Premium Member! Get your 5-day free trial TODAY!

Hello, hello GPCR Buddies! It's starting to look a lot like Christmas at Dr. GPCR! We've got an early holiday treat for you: The University CheatSheet ! Dive into our courses, talks, poster presentations, and more! This Week’s Highlights: Congratulations to our amazing Board Member JoAnn Trejo for being elected to the British Pharmacological Society Honorary Fellowship! 🎉 Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function Szymon P Kordon , Kristina Cechova , Sumit J Bandekar , Demet Araç , et al. Structure-guided design of a peripherally restricted chemogenetic system Hye Jin Kang , Brian E Krumm , Adrien Tassou , Bryan L Roth , et al. 🕶 University CheatSheet is here! We are thrilled to announce that we've been working tirelessly to bring you a simple, beautiful, and insightful collection of all our content! Dive into a world of knowledge where you can search by topics and events . As a Premium Member, you gain exclusive access to this incredible treasure trove we've amassed over the years, featuring excellent speakers from around the globe. We are bursting with pride in sharing it with you, and we sincerely want to thank you for your support over the years. We are ecstatic to create a space where the GPCR Community can thrive with information and INSPIRATION! Listen up, folks! This is your last call before the curtain drops: Classified GPCR News is going VIP-only next year! That's right, all the tidbits below will be for Premium Members ' eyes only. Don't get left in the dust—upgrade now and keep your GPCR gossip game strong! Classified GPCR News  Let’s dive into the   Classified GPCR News from December 2nd to 8th, 2024 Industry News 2024 Fellows and Honorary Fellows announced Nxera Pharma Enrolls First Insomnia Patient in its Phase 3 Clinical Trial of Daridorexant in South Korea Septerna Touches New High, To Report SEP-786 Data In Mid-2025 How GPCR agonists, including antibodies, are shaping the future of metabolic care Salipro Biotech Expands Global Intellectual Property Portfolio with Granted Patents in Australia and Singapore Crinetics Announces FDA Acceptance of New Drug Application for Paltusotine for Adult Patients with Acromegaly GPCR Events, Meetings, and Webinars December 10 - 12, 2024 | Pharmacology 2024 January 13 - 16, 2025 | PepTalk 2025 January 25 - 29, 2025 | SLAS 2025 February 15 - 16, 2025 | Structural and Functional Approaches in GPCR Drug Discovery February 15 - 19, 2025 | BPS 2025 February 16 - 21, 2025 | Harnessing the Power of Advanced Multimodal Approaches to GPCR Drug Discovery March 12 - 14, 2025 | NextGen Biomed 2025 March 25 - 28, 2025 | 10th German Pharm-Tox Summit April 1 - 5, 2025 | XXIII GEM Meeting in 2025 April 3 - 6, 2025 | ASPET 2025 April 14 - 17, 2025 | 20th Drug Discovery Chemistry April 24 - 27, 2025 | American Physiology Summit 2025 April 25 - 30, 2025 | AACR Annual Meeting 2025 May 12 - 15, 2025 | PEGS 2025 May 20 - 22, 2025 | SLAS Europe 2025 June 16 - 19, 2025 | BIO International Convention 2025 July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs GPCR Molecular Pharmacologist Scientist - Biology Scientist I Cell Biology - Tectonic Therapeutic Senior Principal Scientist, Medicinal Chemistry PhD fellowship in GPCR mechanosensing Senior Scientist, GPCR Pharmacology Research Associate - Professor Graeme Milligan Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Adhesion GPCRs Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function GPCR Activation and Signaling P2X7R-primed keratinocytes are susceptible to apoptosis via GPCR-Gβγ-pERK signal pathways Chemogenetic engagement of different GPCR signaling pathways segregates the orexigenic activity from the control of whole-body glucose metabolism by AGRP Neurons Fast-diffusing receptor collisions with slow-diffusing peptide ligand assemble the ternary parathyroid hormone-GPCR-arrestin complex Myosin VI drives arrestin-independent internalization and signaling of GPCRs Corticotropin-releasing factor-like diuretic hormone 44 and five corresponding GPCRs in Drosophila suzukii: Structural and functional characterization Distribution and calcium signaling function of somatostatin receptor subtypes in rat pituitary Synthetic GPCRs for programmable sensing and control of cell behaviour GPCR Binders, Drugs, and more Exploring potential GPR55 agonists using virtual screening, molecular docking and dynamics simulation studies GPCRs in Neuroscience Neuronal cell populations in circumoral nerve ring of sea cucumber Apostichopus japonicus: Ultrastructure and transcriptional profile Adult single-nucleus neuronal transcriptomes of insulin signaling mutants reveal regulators of behavior and learning GPCRs in Oncology and Immunology Short-chain fatty acids and cancer The path of GPR87: from a P2Y-like receptor to its role in cancer progression Ascitic Shear Stress Activates GPCRs and Downregulates Mucin 15 to Promote OvarianCancer Malignancy Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy Methods & Updates in GPCR Research Structure-guided design of a peripherally restricted chemogenetic system Structural and Molecular Insights into GPCR Function AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors Molecular insights into the activation mechanism of GPR156 in maintaining auditory function Become a Premium Member! 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Your go-to hub for everything GPCR! Stay ahead with the latest research breakthroughs, industry updates, job opportunities, and upcoming events—all in one place. Become a Premium Member Welcome to GPCR Weekly News! 🚀 Your go-to hub for everything GPCR! Stay ahead with the latest research breakthroughs, industry updates, job opportunities, and upcoming events —all in one place. 📅 Delivered straight to your inbox every Thursday at 10 AM EST ! 🔑 Premium Members get exclusive access to Classified GPCR News

Stay up to date with the latest GPCR news and insights. Explore Dr. GPCR's classification and dive into the fascinating world of G protein-coupled receptors. Get GPCR news in your inbox every week —be the office genius! Sign Up Fresh Classified GPCR News Adhesion GPCRs Call for GPCR papers Contributors Articles GPCR Activation and Signaling GPCR Binders, Drugs, and more GPCR Events, Meetings, and Webinars GPCR Industry News GPCR Jobs GPCR Weekly News GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Neuroscience GPCRs in Oncology and Immunology Methods & Updates in GPCR Research Reviews, GPCRs, and more Structural and molecular insights into GPCR function Sneak Peek! Content Exclusive for Premium Members* GPCR Weekly News April 17, 2025 Power Up Your GPCR Toolkit: Signals, Structures & Scans Read More April 9, 2025 GPCRs Behaving Strangely? Hidden Patterns in Ligand Binding & Receptor Dynamics Read More April 2, 2025 The GPCR Puzzle: Piecing Together cAMP Bias, GPCR Trafficking, and Biotech Careers Read More Contributors Articles Kiyan Afzali The Perils and Guardrails of Modifying Signalling Proteins in Bioassays Read More John Teye Azietaku Reflections on My PhD Journey: Lessons Learned Read More Cam Sinh Lu Harnessing Deep Mutational Scanning for Enhanced Drug Discovery Read More GPCR Industry News April 14, 2025 Phillip Monk Joins Antiverse as Chief Scientific Officer Read More April 11, 2025 Exicure, Inc. (Nasdaq: XCUR) Announces Their Next Step in Planning for a New Clinical Trial in Acute Myeloid Leukemia (AML) Read More April 10, 2025 Omeros Announces the Omeros Oncology Clinical Steering Committee for AML to Help Guide Omeros’ Proprietary OncotoX-AML Clinical Program Read More GPCR Events, Meetings, and Webinars GPCR Jobs Call for GPCR Papers Special Issue on Adhesion GPCRs Read More November 1, 2024 Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology Read More September 27, 2023 opnMe GPCR Route 66+ project Read More Adhesion GPCRs March 25, 2025 Identification of a GPCR as a tip link-independent equilibrioceptor Read More March 26, 2025 Spatiotemporal profiling of adhesion G protein-coupled receptors in developing mouse and human pancreas reveals a role for GPR56 in islet development Read More February 18, 2025 A force-sensitive adhesion GPCR is required for equilibrioception Read More GPCR Activation and Signaling April 8, 2025 L-asparaginase is a PAR2 N-terminal protease that unmasks the PAR2 tethered ligand Read More April 1, 2025 Diverse Roles of the Multiple Phosphodiesterases in the Regulation of Cyclic Nucleotide Signaling in Dictyostelium Read More April 5, 2025 Activation and signaling characteristics of the hydroxy-carboxylic acid 3 receptor identified in human neutrophils through a microfluidic flow cell technique Read More GPCR Binders, Drugs, and more April 1, 2025 Identification of anti-resorptive GPCRs by high-content imaging in human osteoclasts Read More April 7, 2025 Synthesis and Characterization of Photoswitchable Covalent Ligands for the β2-Adrenoceptor Read More April 4, 2025 Minimal Structural Variation of GPR84 Full Agonist Causes Functional Switch to Inverse Agonism Read More GPCRs in Cardiology, Endocrinology, and Taste April 1, 2025 DRD2-Mediated AMPK Ubiquitination Regulates the Occurrence of Hepatic Steatosis Read More March 29, 2025 Genomic insights into ORs gene family of G protein-coupled receptors expansion driving omnivorous feeding in Spotted knifejaw (Oplegnathus punctatus) Read More April 3, 2025 Formyl-peptide receptor type 2 activation mitigates heart and lung damage in inflammatory arthritis Read More GPCRs in Neuroscience March 31, 2025 Neurokinin 3 receptor agonist senktide stimulates GnRH release in isolated hypogonadotropic hypogonadism mice Read More April 1, 2025 Evidence for Bxy-npr-21 on controlling juveniles' growth and modulating male sexual arousal: from molecules to behaviors Read More April 1, 2025 Characterization of Anthozoan-Specific Opsins from a Reef-Building Coral, Acropora tenuis, as Gq-Coupled Opsins Read More GPCRs in Oncology and Immunology April 10, 2025 SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer Read More April 7, 2025 G-protein coupled receptors in metabolic reprogramming and cancer Read More April 4, 2025 Unveiling the Role of DPYS: A New Prognostic Biomarker in Sarcoma Read More Methods & Updates in GPCR Research April 7, 2025 Topology-Driven Negative Sampling Enhances Generalizability in Protein-Protein Interaction Prediction Read More April 7, 2025 A new approach to psoriasis therapy: photoswitchable A3 adenosine receptor activation Read More March 29, 2025 Sensitive detection of pertussis toxin in acellular pertussis vaccines using HRH1-mediated calcium signaling Read More Reviews, GPCRs, and more April 9, 2025 Where are we now? Biased signalling of Class B G protein-coupled receptor-targeted therapeutics Read More April 1, 2025 Opioid Analgesics: Rise and Fall of Ligand Biased Signaling and Future Perspectives in the Quest for the Holy Grail Read More April 1, 2025 G Protein-Coupled Receptors in Skin Aging Read More Structural and molecular insights into GPCR function April 3, 2025 Proton perception and activation of a proton-sensing GPCR Read More April 9, 2025 Molecular Dynamics (MD) Simulation of GPR87-LPA Binding: Therapeutic Implications for Targeted Cancer Treatment Read More April 4, 2025 Structural basis and biased signaling of proton sensation by GPCRs mediated by extracellular histidine rearrangement Read More UniversityPrice Choose your pricing plan Premium Yearly $ 249.99 249.99$ Every year Select Become Dr. GPCR Strategic Partner