Search Results

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? A Systematic Review and Assessment. Pharmacoeconomics. 2021;39(11):1243-1269. 9.            Brown DG, Wobst HJ, Kapoor A, Kenna LA, Southall N. Clinical development times for innovative drugs. Nat Rev Drug Discov. 2022;21(11):793-794. 10.         Mohs RC, Greig NH. Drug discovery and development: Role of basic biological research. Alzheimers Dement (N Y). 2017;3(4):651-657. 11.         Dowden H, Munro J. Trends in clinical success rates and therapeutic focus. Nat Rev Drug Discov. 2019;18(7):495-496. 12.         Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273-286. 13.         Yamaguchi S, Kaneko M, Narukawa M. Approval success rates of drug candidates based on target, action, modality, application, and their combinations. Clin Transl Sci. 2021;14(3):1113-1122. 14.         Cobey KD, Ebrahimzadeh S, Page MJ, Thibault RT, Nguyen PY, Abu-Dalfa F, et al. Biomedical researchers' perspectives on the reproducibility of research. PLoS Biol. 2024;22(11):e3002870. 15.         Hunter P. The reproducibility "crisis": Reaction to replication crisis should not stifle innovation. EMBO Rep. 2017;18(9):1493-1496. 16.         Liu S, Anderson PJ, Rajagopal S, Lefkowitz RJ, Rockman HA. G Protein-Coupled Receptors: A Century of Research and Discovery. Circ Res. 2024;135(1):174-197. 17.         Kenakin TP. Chapter 2 - How different tissues process drug response. In: Kenakin TP, editor A Pharmacology Primer (Sixth Edition). Academic Press; 2022. p. 23-45. 18.         Lu S, He X, Ni D, Zhang J. Allosteric Modulator Discovery: From Serendipity to Structure-Based Design. Journal of Medicinal Chemistry. 2019;62(14):6405-6421. 19.         Fenton AW. Allostery: an illustrated definition for the 'second secret of life'. Trends Biochem Sci. 2008;33(9):420-5. 20.         Melancon BJ, Hopkins CR, Wood MR, Emmitte KA, Niswender CM, Christopoulos A, et al. Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery. J Med Chem. 2012;55(4):1445-64. 21.         Persechino M, Hedderich JB, Kolb P, Hilger D. Allosteric modulation of GPCRs: From structural insights to in silico drug discovery. Pharmacol Ther. 2022;237:108242. 22.         Chatzigoulas A, Cournia Z. Rational design of allosteric modulators: Challenges and successes. WIREs Computational Molecular Science. 2021;11(6):e1529. 23.         Wodak SJ, Paci E, Dokholyan NV, Berezovsky IN, Horovitz A, Li J, et al. Allostery in Its Many Disguises: From Theory to Applications. Structure. 2019;27(4):566-578. 24.         Changeux J-P, Christopoulos A. Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation. Cell. 2016;166(5):1084-1102. 25.         Motlagh HN, Wrabl JO, Li J, Hilser VJ. The ensemble nature of allostery. Nature. 2014;508(7496):331-339. 26.         Kenakin TP. 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. Pharmacol Rev. 2019;71(2):267-315. 33.         Pearce A, Redfern-Nichols T, Wills E, Rosa M, Manulak I, Sisk C, et al. Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology. J Cell Sci. 2025;138(1). 34.         Kosobokova EN, Skrypnik KA, Kosorukov VS. Overview of Fusion Tags for Recombinant Proteins. Biochemistry (Mosc). 2016;81(3):187-200. 35.         Dave K, Gelman H, Thu CT, Guin D, Gruebele M. The Effect of Fluorescent Protein Tags on Phosphoglycerate Kinase Stability Is Nonadditive. J Phys Chem B. 2016;120(11):2878-85. 36.         Wright SC, Avet C, Gaitonde SA, Muneta-Arrate I, Le Gouill C, Hogue M, et al. Conformation- and activation-based BRET sensors differentially report on GPCR-G protein coupling. Science signaling. 2024;17(841):eadi4747. 37.         Manchanda Y, ElEid L, Oqua AI, Ramchunder Z, Choi J, Shchepinova MM, et al. 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. Pimavanserin exhibits serotonin 5-HT2A receptor inverse agonism for Gαi1- and neutral antagonism for Gαq/11-proteins in human brain cortex. Eur Neuropsychopharmacol. 2020;36:83-89. 42.         Olsen RHJ, English JG. Advancements in G protein-coupled receptor biosensors to study GPCR-G protein coupling. Br J Pharmacol. 2023;180(11):1433-1443. 43.         Olsen RHJ, DiBerto JF, English JG, Glaudin AM, Krumm BE, Slocum ST, et al. TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome. Nature chemical biology. 2020;16(8):841-849. 44.         Wan Q, Okashah N, Inoue A, Nehmé R, Carpenter B, Tate CG, et al. Mini G protein probes for active G protein-coupled receptors (GPCRs) in live cells. J Biol Chem. 2018;293(19):7466-7473. 45.         Nehmé R, Carpenter B, Singhal A, Strege A, Edwards PC, White CF, et al. Mini-G proteins: Novel tools for studying GPCRs in their active conformation. PLoS One. 2017;12(4):e0175642. 46.         Carpenter B, Tate CG. 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. Mol Cell Endocrinol. 2019;488:1-13. 51.         Rößler P, Mayer D, Tsai CJ, Veprintsev DB, Schertler GFX, Gossert AD. GPCR Activation States Induced by Nanobodies and Mini-G Proteins Compared by NMR Spectroscopy. Molecules. 2020;25(24). 52.         Teng X, Chen S, Wang Q, Chen Z, Wang X, Huang N, et al. Structural insights into G protein activation by D1 dopamine receptor. Science advances. 2022;8(23):eabo4158. 53.         Carroll S. Why even physicists still don't understand quantum theory 100 years on. Nature. 2025;638(8049):31-34. 54.         Franzen MM, Alder ML, Dreyer F, Köpp W, Buchholz MB. Being right vs. getting it right: orientation to being recorded in psychotherapeutic interaction as disaffiliative vs. affiliative practice. Front Psychol. 2023;14:1254555. 55.         Hazel S. The paradox from within: research participants doing-being-observed. Qualitative Research. 2015;16(4):446-467. 56.         Wilner W. Participatory experience: the participant observer paradox. Am J Psychoanal. 1987;47(4):342-57. 57.         Lowe D. Fluorescent Tags Are Basically Never Silent. In the Pipeline  (Science, 2024).   Acknowledgements Figures in this article were created with the assistance of BioRender.com

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! Get your 5-day free trial TODAY!

Elevate your GPCR visibility Join our exclusive media partner program—just 12 CROs accepted per year You’ve built incredible tools, services, or platforms for GPCR researchers. But are the right scientists discovering them? Dr. GPCR is the world’s largest nonprofit community focused on GPCRs. As a media partner, you’ll gain trusted access to an engaged audience of academic researchers, biotech teams, and drug discovery innovators—without having to fight for attention. We only accept 12 media partners per year. Each one receives personalized support, targeted visibility, and a seat at the table in the GPCR ecosystem. Ready to share your tools with the GPCR world? Partner today! Why Partner with Dr. GPCR? As a media partner, you’ll be featured across our nonprofit platform trusted by thousands of GPCR scientists and biotech professionals. We’ll help you: Reach qualified researchers who are actively looking for tools like yours Build trust through content that speaks their language Contribute to a collaborative, curated ecosystem—not a crowded vendor list With only 11 seats remaining in 2025, we’re focused on quality over quantity—and on partnerships that deliver long-term value to the field. What you get as Media Partner Becoming a Dr. GPCR media partner means more than visibility. It means integration into a trusted scientific ecosystem that’s built to elevate your story, showcase your expertise, and connect you with the scientists who need your solutions most. Here’s what’s included: 🎙️ Featured Podcast Episode Be the guest on a dedicated episode of the Dr. GPCR Podcast— the most respected voices in the field. We’ll feature up to 3 members of your team to share your story, walk through your capabilities, and highlight the impact you’re making in GPCR research. Episodes are distributed across podcast platforms, social media, and the Dr. GPCR Ecosystem homepage. 📄 Custom Company Page on the Dr. GPCR Ecosystem We’ll create a permanent company profile on the Dr. GPCR Ecosystem, including: ● Logo & branding ● Description of your mission and offerings ● Contact links and key highlights You provide the materials—we make it shine. 🧰 Product or Service Pages Go deep into your offerings with individual pages for each product or service. Use these pages to educate researchers, showcase technical value, and provide downloadable resources or use cases. 📬 Newsletter Visibility You’ll be featured in our highly read weekly newsletter, reaching GPCR scientists across academia and industry. But this isn’t just a logo drop—we help you tell your story with context, clarity, and purpose. 🎧 Bonus: You’ll also be mentioned in podcast intros/outros for added exposure. 📣 Social Media Promotion We’ll craft engaging posts about your organization for LinkedIn and X (Twitter), targeted to GPCR researchers and biotech professionals. 👩🔬 Scientist Licenses (10 included) Your scientific team will receive 10 Premium Dr. GPCR Ecosystem accounts. These licenses unlock access to GPCR University courses, curated news, job boards, and research-focused content—designed to keep scientists informed, connected, and engaged with the latest in GPCR drug discovery. 🧑💼 Non-Scientist Licenses (3 included) Your business development, operations, or marketing colleagues will receive 3 Premium accounts tailored to help them stay plugged into the GPCR community. They’ll get access to member-only news, events, and visibility tools—perfect for supporting outreach, partnerships, and strategy. 📝 Blog Contributions (Yearly Glow only) As a partner, you’ll have the opportunity to contribute to blog posts on the Dr. GPCR platform. Whether it’s a product launch, scientific insight, or customer story, we’ll help share it with a targeted scientific audience. 🎤 Co-Branded Events & Training Sessions We’ll collaborate on webinars, virtual training sessions, or educational events to highlight your expertise. These can be live or recorded, and hosted on the Dr. GPCR platform for extended reach. 🐝 With only 12 media partner seats available each year, every partner gets intentional placement, dedicated support, and real visibility. No noise. No clutter. Just connection. Partnership Packages 🔦 Monthly Spotlight $5.000 One partnership per month Booking 30 days prior required Subject to availability 🎙️ One featured podcast episode (up to 3 team members) 🏢 Dedicated company page on the Dr. GPCR Ecosystem 📬 One newsletter mention 📣 One social media post 🎧 Company mention in podcast intros/outros 📊 Performance summay 📆 Monthly slots are limited to a small number of partners each quarter—designed for focus and visibility. ✨ Yearly Glow $10.000 Subject to availability Everything in the Monthly Spotlight package 📬 Monthly newsletter features 🧰 Unlimited product/service pages 👩🔬 10 Premium licenses for scientists 🧑💼 3 Premium licenses for non-scientists 📝 Monthly blog contribution opportunities 🎤 Option to co-host webinars or virtual events 📊 Performance summaries and ongoing content guidance 🐝 Only 12 Yearly Glow seats are available each year to keep our ecosystem curated, impactful, and community-focused. Apply today Present & Previous Partners

Home Services CRO CSO Blog Contact About Get in Touch Home: Welcome Accelerating GPCR Discovery Through Strategy, Systems, and Scientific Alignment If your discovery efforts feel slow or scattered, I can help. I work at the intersection of biotech, CROs, and investors — guiding assay strategy, optimizing CRO selection and communication, and building scientific systems that deliver decision-ready data faster. Help My GPCR Program Yamina A. Berchiche, Ph.D. I help biotech teams, CROs, and investors accelerate GPCR discovery by aligning assay strategy, infrastructure, and people. With two decades of experience in GPCR pharmacology and leadership roles in biotech, I bring both scientific depth and operational clarity to every engagement. Whether it's selecting the right CRO, designing internal capabilities, or translating data into decisions, I work alongside your team to eliminate friction and build momentum. As the founder of Dr. GPCR, I also bring deep community insight and trusted connections across the field. Start the Conversation Meet the Team This is your Team section. Briefly introduce the team then add their bios below. Click here to edit. Art Director Ashley Jones Add a short bio for each team member. Make it brief and informative to keep visitors engaged. Tech Lead Don Francis Add a short bio for each team member. Make it brief and informative to keep visitors engaged. Product Manager Alexa Young Add a short bio for each team member. Make it brief and informative to keep visitors engaged. Yamina Menu Yamina's Corner Home Get in Touch CRO CSO Consulting Legal ©2023-2025 All rights reserved by FindYooour, Llc Proudly created with Wix.com Follow me: LinkedIn X

We aspire to provide opportunities to connect, grow, and thrive as a great GPCR Community. We dream of a world where most of us lead a fulfilling and healthy life. Home: About Welcome to Dr. GPCR Ecosystem We dream of a world where the vast majority of us lead a fulfilling and healthy life. Sign Up Today! We aspire to provide opportunities to connect, grow, and thrive as a great GPCR Community. What did you miss from the Dr. GPCR Ecosystem? GPCR Courses GPCR Flash News GPCR Weekly News Dr. GPCR Podcast Contributors Articles Our Vision Closing the gap ( between academia and industry ) and accelerating drug discovery. Home: Contact Add terms and conditions Best Value Premium Yearly $249.99 $ 249.99 Every year Valid until canceled Select Become a Premium member and be part of the vision Find a pricing plan that works for you