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

Hello GPCR people! We have great news! This week we’ve curated 18 GPCR papers, 1 new event, 9 industry news, and 3 job opportunities! Take a few minutes, and dive into our GPCR coverage! We welcome GPCR paper suggestions! Submit your publications to Hello@DrGPCR.com for consideration. This week's highlight: Thank you to Dr. Tobias Langenhan for his papers to highlight suggestions GAIN Domain Unfolding in Adhesion GPCRs Molecular Sensing in Adhesion GPCR Dissociation Physiological Force Modulation in Drosophila Neurons Dr. David Gloriam and his team present GproteinDb in 2024 Are you looking to hire? Or maybe looking for your next opportunity? Let Mark Schmeizl, our Chief Matchmaker help. Contact him by filling out this form. Our November Dr. GPCR Newsletter is now available. This month's video newsletter features Dr. Alix Rouault as our special guest. Subscribe now! Don't miss the upcoming episodes of Dr.GPCR Podcast featuring Dr. Neil Grimsey and Dr. Katarzyna Marcinkiewicz. Now check out the weekly Classified GPCR News from November 20th to 26th, 2023. Adhesion GPCRs The Posttraumatic Increase in the Adhesion of GPCR EMR2/ ADGRE2 to Circulating Neutrophils Is Not Related to Injury Severity Unveiling Mechanical Activation: GAIN Domain Unfolding and Dissociation in Adhesion GPCRs Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation GPCR Activation and Signaling GPR101: Modeling a constitutively active receptor linked to X-linked acrogigantism The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis GPCR Binders, Drugs, and more Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays GPCRs in Oncology and Immunology RGS5 maintaining vascular homeostasis is altered by the tumor microenvironment High Metabolite Concentrations in Portal Venous Blood as a Possible Mechanism for Microbiota Effects on the Immune System, and Western Diseases Lactate receptor GPR81 drives breast cancer growth and invasiveness through regulation of ECM properties and Notch ligand DLL4 Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5 Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant Methods & Updates in GPCR Research GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions Experimental modulation of physiological force application on leg joint neurons in intact Drosophila melanogaster Reviews, GPCRs, and more Catecholamine Derivatives: Natural Occurrence, Structural Diversity, and Biological Activity Advances in steroid research from the pioneering neurosteroid concept to metabolomics: New insights into pregnenolone function Molecular characterization of lumpy skin disease virus from recent outbreaks in Pakistan Structural and Molecular Insights into GPCR Function Structural and signaling mechanisms of TAAR1 enabled preferential agonist design Proteome-wide structural analysis quantifies structural conservation across distant species Industry News Avantor's (AVTR) New Offerings to Aid Cell and Gene Therapy Suite Avantor® Expands Cellular Science Offerings with Multispan Cell Engineering and Assay Services $3bn sales potential for drug Sosei Heptares wants back from GSK Novartis drops subpoena request in trade-secret spat with Takeda Novartis showcases significant data updates from Kisqali®, iptacopan and Scemblix® at SABCS and ASH Research reveals pro-phagocytic function and structural basis of GPR84 signaling Advancements in Precision Medicine: Superluminal Medicines Inc. Showcases Innovative AI-Driven Drug Design at BRIC AI 2023 Workshop Salipro Biotech AB Celebrates Milestones in CryoEM Structures and In Vitro Binding Assays Through Collaboration with Sanofi Genentech and NVIDIA Enter Into Strategic AI Research Collaboration to Accelerate Drug Discovery and Development GPCR Events, Meetings, and Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition NEW 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 October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs - Contact Mark Schmeizl NEW Scientist NEW Lead Researcher NEW Post-Doctoral Fellow Sr Scientist in Obesity, Muscle, and Metabolism Post-Doctoral Fellow Research Associate I, Tissue Culture Post-Doc Research Associate Postdoctoral Fellow Explore Dr. GPCR Ecosystem

Hi there readers! This week we’ve curated 13 GPCR papers, 1 new event, 11 industry news, and 3 job offers! Check out our GPCR roundup now, and be the first to read! This week's highlight: Drs. Brian Krumm and Bryan Roth studied CryoEM structures of adhesion in GPCR CD97, filling gaps. Last Friday was our final Dr. GPCR Symposium for the year, focusing on GPCRs in Immunology and Oncology, concluding the Dr. GPCR Symposia 2023. We extend immense gratitude to our exceptional speakers and all attendees who participated. For those who joined any of our symposium sessions, we kindly request a moment of your time to fill out our survey. If you weren't able to attend, don't worry – our premium members have continuous access to revisit and watch the archived presentations at any time HERE. Sign up for Dr. GPCR Newsletter and stay ahead of the curve with news on the Dr. GPCR University live courses we are preparing for you in 2024. Now let’s dive into the weekly Classified GPCR News from November 13th to 19th, 2023. Adhesion GPCRs CryoEM structures of adhesion in GPCR CD97: Filling in some of the gaps GPCR Activation and Signaling Butyrate induces STAT3/HIF-1α/IL-22 signaling via GPCR and HDAC3 inhibition to activate autophagy in head kidney macrophages from turbot (Scophthalmus maximus L.) Endosomal signaling via cAMP in parathyroid hormone (PTH) type 1 receptor biology β-arrestin1 is an E3 ubiquitin ligase adaptor for substrate linear polyubiquitination GPCR Binders, Drugs, and more Dual allosteric and orthosteric pharmacology of synthetic analog cannabidiol-dimethylheptyl, but not cannabidiol, on the cannabinoid CB2 receptor GPCRs in Cardiology, Endocrinology, and Taste Transcriptomic changes in glomeruli in response to a high salt challenge in the Dahl SS rat GPCRs in Neuroscience Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor NTR-1's Essential Contribution to Asymmetric Mating Between Two Sibling Nematode Species: Bursaphelenchus xylophilus and B. mucronatus GPCRs in Oncology and Immunology GPCR signaling contributes to immune characteristics of microenvironment and process of EBV-induced lymphomagenesis GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma Methods & Updates in GPCR Research Optogenetic Microwell Array Screening System: A High-Throughput Engineering Platform for Genetically Encoded Fluorescent Indicators Design of an effective small expression tag to enhance GPCR production in E. coli-based cell-free and whole cell expression systems A high-throughput structural dynamics approach for identification of potential agonists of FFAR4 for type 2 diabetes mellitus therapy Industry News OMass Therapeutics Welcomes Melissa Faris as Chief Business Officer Septerna: Revitalizing G-Protein Coupled Receptor Drug Discovery Orion’s VP Drug Discovery, Dr. Oliver Hartley, was at the PEGS Europe Novartis pays Legend $100M upfront to give solid tumor CAR-T the T-Charge treatment Innovation And Healthcare Meet At Novartis Neurocrine Biosciences Announces Settlement of INGREZZA Abbreviated New Drug Application (ANDA) Litigation PostEra Announces a Research Collaboration with Amgen to Discover Small Molecule Therapeutics using Artificial Intelligence Novo Nordisk Invests 42 Billion Danish Kroner in New Manufacturing Facilities Addex ADX71149 Epilepsy Phase 2 Study Completes Recruitment of Patients Sanyou Bio's Evolution of Bioprocess Enhancement for CHO Cell Lines: A Talk by Dr. Meiling Lim TRUQAP™ (capivasertib) plus fulvestrant approved in the US for patients with advanced HR-positive breast cancer GPCR Events, Meetings, and Webinars November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition 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 NEW 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 October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs NEW Sr Scientist in Obesity, Muscle, and Metabolism NEW Post-Doctoral Fellow NEW Research Associate I, Tissue Culture Post-Doc Research Associate Postdoctoral Fellow Research Scientist/Postdoctoral Associate in Computational Chemistry/Biophysics Post-Doctoral Associate Team Leader Antibody Discovery Explore Dr. GPCR Ecosystem

Hi, everyone! This week, we've curated 12 GPCR papers. Plus, don't miss out on 6 upcoming events, 2 new job offers, and 9 industry updates. Let’s dive in! Save the date: TOMORROW - November 17: Don't miss out on our final Dr. GPCR Symposium for the year, which will focus on GPCRs in Immunology and Oncology. A panel of top experts will be discussing this topic in a roundtable, starting at 10:00 AM EST. You can find more details about the speakers on the Live Talks page, and make sure to mark your calendar for this important event! Discover the latest monthly Dr. GPCR Newsletter with Dr. Kathleen Caron, as our video guest, subscribe now! Now check out the weekly Classified GPCR News from November 6th to 12th, 2023. GPCR Activation and Signaling Neuronal survival factor TAFA2 suppresses apoptosis through binding to ADGRL1 and activating cAMP/PKA/CREB/BCL2 signaling pathway Deciphering specificity and cross-reactivity in tachykinin NK1 and NK2 receptors GPCR Binders, Drugs, and more Discovery of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid derivatives as a new class of GPR34 antagonists Larixol is not an inhibitor of Gαi containing G proteins and lacks effect on signaling mediated by human neutrophil expressed formyl peptide receptors Molecular recognition of niacin and lipid-lowering drugs by the human hydroxycarboxylic acid receptor 2 GPCRs in Cardiology, Endocrinology, and Taste Lack of HCAR1, the lactate GPCR, signaling promotes autistic-like behavior Acetate mitigates cardiac mitochondrial dysfunction in experimental model of polycystic ovarian syndrome by modulating GPCR41/43 and PROKR1 GPCRs in Neuroscience Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease GPCRs in Oncology and Immunology Context-dependent ciliary regulation of hedgehog pathway repression in tissue morphogenesis TIPE proteins control directed migration of human T cells by directing GPCR and lipid second messenger signaling Methods & Updates in GPCR Research An image-based abplex method for high-throughput gpcrs antibody discovery Reviews, GPCRs, and more Current strategic trends in drug discovery: the present as prologue Industry News Exscientia Business Update for Third Quarter 2023 Addex CEO Tim Dyer to Discuss Allosteric Modulators in Neurological Disorders at Jefferies Healthcare Conference in London Sosei Heptares and Kallyope Nominate First GPCR Target for Therapeutic Development in Gastrointestinal Diseases Sosei Heptares Operational Highlights and Consolidated Results for the Third Quarter and First Nine Months of 2023 InterAx Biotech Announces Being the Recipient of a Highly Competitive European Grant to Fund Drug Development and Reports Financing Highlights Neurocrine Biosciences Provides Development Pipeline Update Crinetics Pharmaceuticals Announces November 2023 Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) GPCR signaling contributes to immune characteristics of the microenvironment and the process of EBV-induced lymphomagenesis Tanso Biosciences: Core Technology for Our GPCR Functional Assay Patented in Japan GPCR Events, Meetings, and Webinars November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting NEW January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition NEW 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 NEW April 1 - 4, 2024 | 19th Annual Drug Discovery Chemistry April 5 - 10, 2024 | AACR Annual Meeting NEW 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 October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry NEW July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology 2026 GPCR Jobs NEW Post-Doc Research Associate NEW Postdoctoral Fellow Research Scientist/Postdoctoral Associate in Computational Chemistry/Biophysics Post-Doctoral Associate Team Leader Antibody Discovery Staff Scientist (AC-TAP) in Database Development at Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences Octant Apprentice Explore Dr. GPCR Ecosystem

Good day, GPCR folks! Take advantage of our GPCR highlights of the week. Dr. Hannes Schihada and his lab team developed fluorescent analogues for real-time binding studies of orphan GPCR GPR3: Save the dates: November 17: Join our final Dr. GPCR Symposium for the year on GPCRs in Immunology and Oncology! A panel of top experts will discuss in a roundtable starting at 10 AM EST. Find speaker details on the Live Talks page and mark your calendar HERE. You don't want to miss out on our monthly Dr. GPCR Newsletter for exclusive content, check out our latest video featuring Dr. Kathleen Caron. Check out the weekly Classified GPCR News from October 30 to November 4, 2023. GPCR Activation and Signaling The G protein alpha chaperone and guanine-nucleotide exchange factor RIC-8 regulates cilia morphogenesis in Caenorhabditis elegans sensory neurons CaSR links endocytic and secretory pathways via MADD, a Rab11A effector that activates Rab27B Targeting of insulin receptor endocytosis as a treatment to insulin resistance Stepwise phosphorylation of BLT1 defines complex assemblies with β-arrestin serving distinct functions Phosphorylation motif dictates GPCR C-terminal domain conformation and arrestin interaction Ready for the sheet: β-strand folding of phosphorylation clusters guides GPCR binding to arrestin Dietary dibutyryl cAMP supplementation regulates the fat deposition in adipose tissues of finishing pigs via cAMP/PKA pathway GPCR Binders, Drugs, and more Cloning and deorphanization of three inotocin (insect oxytocin/vasopressin-like) receptors and their ligand from the tick Ixodes scapularis Evidence that pyrophosphate acts as an extracellular signalling molecule to exert direct functional effects in primary cultures of osteoblasts and osteoclasts Development of Fluorescent AF64394 Analogues Enables Real-Time Binding Studies for the Orphan Class A GPCR GPR3 Antimalarial and Plasmodium falciparum serpentine receptor 12 targeting effect of FDA approved purinergic receptor antagonist GPCRs in Cardiology, Endocrinology, and Taste Palmitoylation-Dependent Regulation of Cardiomyocyte Rac1 Signaling Activity and Minor Effects on Cardiac Hypertrophy Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21 GPCRs in Neuroscience Pregabalin inhibits purinergic P2Y2 receptor and TRPV4 to suppress astrocyte activation and to relieve neuropathic pain GPCRs in Oncology and Immunology Systems Pharmacodynamic Model of Combination Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part II: Cell Cycle, DNA Damage Response, and Apoptosis Pathways Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia Methods & Updates in GPCR Research Mining the ZINC database of natural products for specific, testosterone-like, OXER1 antagonists A 19F-qNMR-Guided Mathematical Model for G Protein-Coupled Receptor Signaling Optical Approaches for Investigating Neuromodulation and G Protein-Coupled Receptor Signaling Protocol for identifying physiologically relevant binding proteins of G-protein-coupled receptors Reviews, GPCRs, and more RGS proteins and cardiovascular Angiotensin II Signaling: Novel opportunities for therapeutic targeting Recent progress in degradation of membrane proteins by PROTACs and alternative targeted protein degradation techniques Ligand selectivity hotspots in serotonin GPCRs Study of G protein-coupled receptors dimerization: From bivalent ligands to drug-like small molecules Structural and Molecular Insights into GPCR Function Hydrophobic interaction between the TM1 and H8 is essential for rhodopsin trafficking to vertebrate photoreceptor outer segments Industry News Sosei Heptares Will Receive US$3.75 Million Payment in Multi-Target Partnership Sosei Heptares Announces Submission of New Drug Application in Japan for Daridorexant (ACT-541468), a Dual Orexin Receptor Antagonist for the Treatment of Insomnia OMass Therapeutics Releases First Protein Structures in PDB, Advances Lupus Therapy Research Structure Therapeutics Receives R&D Achievement of the Year Award for GPCR Research Bryan Roth, Natural Products, and the John Daly Legacy Sosei Heptares’ Partner, Pfizer, Progresses Its GLP-1 Receptor Agonist PF-06954522 into a Phase 1 Trial Andrew Hopkins Inducted into RSC BMCS Hall of Fame and Receives Associated Medal in 2023 'This field is in its infancy': Amgen noncommittal on oral obesity med until phase 1 data arrive Form and Function - Consequences of subcellular cAMP signaling revealed AI Predicts How GPCRs Respond to Drug-Like Molecules Accurately predicting GPCR P2Y1 membrane protein ligand binding with Free Energy Perturbation GPCR Events, Meetings, and Webinars November 10, 2023 | Sosei Heptares Zoom Webinar November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 GPCR Jobs NEW Research Scientist/Postdoctoral Associate in Computational Chemistry/Biophysics NEW Post-Doctoral Associate NEW Team Leader Antibody Discovery Staff Scientist (AC-TAP) in Database Development at Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences Octant Apprentice Head of Human Resource Business Partners Senior Scientist, In vitro pharmacology - Crinetics Pharmaceuticals Senior Director, In vitro pharmacology - Crinetics Pharmaceuticals Explore Dr. GPCR Ecosystem

Hi there GPCR minds! Join us for a deep dive into the world of GPCRs. If you're attending the GPCR Retreat, be sure to swing by our booth and snap a photo at our banner! Plus, don't forget to ask for your special treat. We're proud sponsors and can't wait to connect with all of you. See you there! This week's highlight: Congratulations to the GPCR Therapeutics team for their publication on improving hematopoietic stem cell mobilization using Propranolol. Save the dates: November 17: Join our final Dr. GPCR Symposium for the year on GPCRs in Immunology and Oncology! A panel of top experts will discuss in a roundtable starting at 10 AM EST. Find speaker details on the Live Talks page and mark your calendar HERE. Get the inside scoop by subscribing to our monthly Dr. GPCR Newsletter, and watch our latest video featuring Dr. Kathleen Caron. Check out the weekly Classified GPCR News from October 23rd to 29th, 2023. GPCR Activation and Signaling The GPCR adaptor protein Norbin regulates S1PR1 trafficking and the morphology, cell cycle and survival of PC12 cells GLP-1 and GIP receptors signal through distinct β-arrestin 2-dependent pathways to regulate pancreatic β cell function GPCR Binders, Drugs, and more GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol Discovery of 3-Phenyl Indazole-Based Novel Chemokine-like Receptor 1 Antagonists for the Treatment of Psoriasis GPCRs in Cardiology, Endocrinology, and Taste Ageing influences detrusor contractions to prostaglandin, angiotensin, histamine and 5-HT (serotonin), independent to the Rho kinase and extracellular calcium pathways Versatile lactate signaling via HCAR1: a multifaceted GPCR involved in many biological processes GPCRs in Neuroscience Dopaminergic Input Regulates the Sensitivity of Indirect Pathway Striatal Spiny Neurons to Brain-Derived Neurotrophic Factor GPCRs in Oncology and Immunology Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies Methods & Updates in GPCR Research ThermoBRET: A Ligand-Engagement Nanoscale Thermostability Assay Applied to GPCRs Reviews, GPCRs, and more Illuminating the druggable genome: Pathways to progress Industry News Anatole Klepatsky, Orion's COO, Shared Innovative Insights at LSBC Central European Life Science Investment Conference GPCR Therapeutics Announces Publication on Improving Hematopoietic Stem Cell Mobilization Using Propranolol with GPC-100 Sosei Heptares to Host R&D Day Highlighting its Innovative R&D and Late-Stage Development Progress Parker Moss to Join Exscientia as EVP, Corporate Development Confo Therapeutics Nominated for 'Deal of the Year (>€500 Million)' Award at European Lifestars Awards GPCR Events, Meetings, and Webinars November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 10, 2023 | Sosei Heptares Zoom Webinar November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 GPCR Jobs NEW Staff Scientist (AC-TAP) in Database Development at Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences NEW Octant Apprentice Head of Human Resource Business Partners Senior Scientist, In vitro pharmacology - Crinetics Pharmaceuticals Senior Director, In vitro pharmacology - Crinetics Pharmaceuticals In vivo Antibody Discovery Research Scientist In Vitro Biologist/Molecular Pharmacologist Explore Dr. GPCR Ecosystem

Exploring the intracellular allosteric site GPCRs represent one of the largest and most vital families of cell surface receptors, playing a pivotal role in cellular signaling. For this reason, GPCRs have been a focus of drug development for decades due to their role in regulating essential physiological processes. Conventional GPCR drug discovery has largely focused on orthosteric sites, but recent breakthroughs in understanding allosteric modulation have opened up new avenues for drug development. Recent advances in structural biology and pharmacology have revealed the existence of allosteric sites within GPCRs' intracellular domains. These sites act as molecular switches that can modulate receptor activity, providing an untapped opportunity for drug discovery. Unlike orthosteric ligands that bind directly to the receptor's active site, allosteric modulators target distinct, often less conserved sites on the receptor. This allows for the fine-tuning of receptor activity, leading to more specific and safer drugs. Allosteric binding sites on the receptor are those topographically distinct from (do not exhibit any overlap with) the orthosteric site (Rosenbaum, Rasmussen et al. 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 et al. 2011). Allosteric ligands can be classified as positive allosteric modulators (PAMs), which increase the receptor functional and/or affinity for an orthosteric ligand; and negative allosteric modulators (NAMs), that fully or partially dampen the receptor's functional response to the ligand (Wold, Chen et al. 2019). Alternatively, they can function as neutral allosteric ligands (NALs), binding to a receptor's allosteric site without causing any detectable alterations in the receptor or orthosteric ligand behavior (Lindsley, Emmitte et al. 2016). However, a NAM competes for binding with PAMs and NAMs and thereby blocks the effects of positive and negative allosteric modulators (Rodriguez, Nong et al. 2005). Allosteric modulators targeting GPCRs can display one or more of the following pharmacological characteristics: 1) affinity modulation where the resulting change in conformation can influence the orthosteric binding pocket, potentially altering the rate of association, dissociation, or both, of an orthosteric ligand; 2) efficacy modulation where there are modifications in intracellular responses, consequently affecting intrinsic efficacy of the orthosteric ligand; 3) agonism/inverse agonism, where the allosteric modulator can perturb receptor signaling in a manner that is either positive (agonism) or negative (inverse agonism), regardless of whether an orthosteric ligand is present or absent (May, Leach et al. 2007). Advantages of targeting GPCRs allosteric sites Allosteric sites offer a more nuanced approach to modulating GPCR activity, enabling greater specificity and fewer side effects. 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 (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). 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, Gregory 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, Chen et al. 2019). Biased allosteric mechanisms Allosteric sites can differentially modulate G-protein and β-arrestin coupling, enabling the development of biased agonists and antagonists with distinct therapeutic potential. Allosteric antagonists are compounds that inhibit GPCR activity by binding to intracellular allosteric sites. G-protein-biased allosteric antagonists are under investigation for several GPCRs, including CCR2, CCR7, CCR9, CXCR2, and β2AR. Interestingly, although having different chemical structures they exhibit strikingly similar binding positions on their respective receptors. On the other hand, positive allosteric modulators that target intracellular allosteric sites can enhance β-arrestin-mediated signaling pathways. SBI-553, an allosteric modulator of NTSR1, provides valuable insights into how allosteric modulation can selectively enhance β-arrestin-mediated signaling. Structural studies at high resolution have illuminated the intricate interactions between NTSR1 and GRK2. Allosteric agonists binding to intracellular sites can also promote G-protein signaling. PCO371 is a G-protein-biased allosteric agonist for the adenosine receptor A1, with the promise to improve cardiac contractility. Recent advances in structural biology have allowed researchers to visualize the binding of allosteric agonists like PCO371 to Gs-proteins, further elucidating biased signaling mechanisms. The process of designing and evaluating biased ligands for GPCRs is complex but essential for understanding their diverse signaling pathways. Advances in understanding the structural and mechanistic aspects of biased GPCR signaling are crucial for designing effective drug molecules. Additionally, considering conformational kinetics for coupling preference with downstream signaling components, such as β-arrestin and G-protein transducers, is important. Allosteric modulation is gaining prominence in GPCR therapeutics, with the discovery of an intracellular allosteric site common in class A and class B GPCRs, particularly in chemokine receptors. This site allows for the direct modulation of downstream receptor signaling in an allosteric manner. Biased allosteric modulators can enhance the safety and efficacy of GPCR-targeted therapeutics by selectively targeting specific signaling pathways. Notably, SBI-553 and PCO371 have been identified as BAMs with intracellular allosteric binding sites. These findings provide a comprehensive understanding of GPCR biased signaling induced by intracellular allosteric agonists and establish a strong foundation for developing biased drugs targeting GPCRs. Check the original article at https://pubmed.ncbi.nlm.nih.gov/37852356/ #GPCR #DrGPCR #Ecosystem

Hey there! Are you ready for some exciting news in the GPCR world? This week's highlights: Dr. Bianca Plouffe and their colleagues' research on 'β-arrestin-dependent and -independent endosomal GPCR activation by the V2.' Norton Cheng and Dr. JoAnn Trejo's study 'identifies two deubiquitinases that regulate GPCR-p38 MAPK signaling and distinct inflammatory responses.' Dr. Robert J Lefkowitz and team's study 'GPCR signal transduction: β-arrestin activates ERK MAPK.' Dr. Thomas P. Sakmar and his team used 'bioluminescence resonance energy transfer to measure cell-surface expression of membrane proteins.' Save the dates: November 2 - 4: We're sponsoring the GPCR Retreat and would love to meet you there! Submit your logo design by Nov 1st on the Logo Contest page. No registration is required to participate. November 17: Join our last Dr. GPCR Symposium of the year on GPCRs in Immunology and Oncology! We've gathered a panel of top experts for a roundtable discussion starting at 10 a.m. EST. Our confirmed speakers are Dr. Xavier Leroy, Dr. Brian Arey, and Dr. J. Silvio Gutkind. You can find more information about them on the Live Talks page and mark your calendar HERE. Subscribe to Dr. GPCR Newsletter for more insights! Check out the weekly Classified GPCR News from October 16th to 22nd, 2023. GPCR Activation and Signaling β-Arrestin-dependent and -independent endosomal G protein activation by the vasopressin type 2 receptor An siRNA library screen identifies CYLD and USP34 as deubiquitinases that regulate GPCR-p38 MAPK signaling and distinct inflammatory responses State-dependent dynamics of extramembrane domains in the β2 -adrenergic receptor Signal transduction at GPCRs: Allosteric activation of the ERK MAPK by β-arrestin GPCR Binders, Drugs, and more Pharmacologically targeting intracellular allosteric sites of GPCRs for drug discovery Targeting mGluR group III for the treatment of neurodegenerative diseases GPCRs in Neuroscience Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling Ciliary localization of a light-activated neuronal GPCR shapes behavior Methods & Updates in GPCR Research Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery Application of bioluminescence resonance energy transfer to quantitate cell-surface expression of membrane proteins Structural and Molecular Insights into GPCR Function Molecular property, manipulation, and potential use of Opn5 and its homologs Industry News The Leading GPCR Company in Immuno-Oncology, Domain Therapeutics, Presents Groundbreaking Advancements at ESMO 2023 Novo Nordisk to Buy Hypertension Treatment from KBP Biosciences Exscientia to Present New Preclinical Data for AI-designed LSD1 and MALT1 Inhibitors at ESMO 2023 Restoring the function of a human cell surface protein in yeast cells Trevena Reports Favorable TRV045 Topline Safety and Tolerability Data from Proof-of-Concept Studies Sosei Heptares’ President & CEO Chris Cargill Wins Executive of the Year at the Citeline Pharma Intelligence Awards Japan 2023 BioMap and Sanofi to co-develop AI modules for biotherapeutic drug discovery Novartis Kisqali® NATALEE analysis reinforces consistent reduction in risk of recurrence across key subgroups of patients with early breast cancer GPCR Events, Meetings, and Webinars October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 GPCR Jobs Head of Human Resource Business Partners Senior Scientist, In vitro pharmacology - Crinetics Pharmaceuticals Senior Director, In vitro pharmacology - Crinetics Pharmaceuticals In vivo Antibody Discovery Research Scientist In Vitro Biologist/Molecular Pharmacologist Senior Vice President, Oncology Clinical Research Scientist (level I or II) Explore Dr. GPCR Ecosystem

Hi, everyone! Read about the newest discoveries in GPCR research 🙌 Save the dates: November 2 - 4: We're sponsoring the GPCR Retreat and would love to meet you there! Submit a logo design by Nov 1st on the Logo Contest page. No registration is needed to submit your logo design. Subscribe to Dr. GPCR Newsletter to receive more insights! Now check out the weekly Classified GPCR News from October 9th to 15th, 2023. Adhesion GPCRs Piconewton Forces Mediate GAIN Domain Dissociation of the Latrophilin-3 Adhesion GPCR Unveiling Mechanical Activation: GAIN Domain Unfolding and Dissociation in Adhesion GPCRs GPCR Activation and Signaling Diuretic hormone 31 activates two G protein-coupled receptors with differential second messengers for diuresis in Drosophila suzukii Beyond the G protein α subunit: investigating the functional impact of other components of the Gαi3 heterotrimers Activation/Deactivation Free-Energy Profiles for the β2-Adrenergic Receptor: Ligand Modes of Action A non-pheromone GPCR is essential for meiosis and ascosporogenesis in the wheat scab fungus GPCR Binders, Drugs, and more Development of Photoswitchable Tethered Ligands that Target the µ-Opioid Receptor Design and Synthesis of Novel GPR139 Agonists with Therapeutic Effects in Mouse Models of Social Interaction and Cognitive Impairment GPCRs in Neuroscience The Drosophila blood-brain barrier regulates sleep via Moody G protein-coupled receptor signaling GPCRs in Oncology and Immunology Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report GPR37 expression as a prognostic marker in gliomas: a bioinformatics-based analysis Reviews, GPCRs, and more Parallel evolution of the G protein-coupled receptor GrlG and the loss of fruiting body formation in the social amoeba Dictyostelium discoideum evolved under low relatedness Industry News Nobel Laureates Highlight Symposium Celebrating Lefkowitz’s 50 Years at Duke Novo Nordisk stops Ozempic kidney trial after early signs of success Sosei and PharmEnable extend neurological disease drugs hunt Sosei Heptares’ President & CEO Chris Cargill Wins Executive of the Year at the Citeline Pharma Intelligence Awards Japan 2023 Salipro Biotech and Icosagen Launch Antibody Discovery Collaboration Cryo-EM in Drug Discovery GPCR Events, Meetings, and Webinars NEW October 19, 2023 | ERNEST ECI Zoominar October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW Head of Human Resource Business Partners Senior Scientist, In vitro pharmacology - Crinetics Pharmaceuticals Senior Director, In vitro pharmacology - Crinetics Pharmaceuticals In vivo Antibody Discovery Research Scientist In Vitro Biologist/Molecular Pharmacologist Senior Vice President, Oncology Clinical Research Scientist (level I or II) Research Fellow Research Technician II - Surgery Explore Dr. GPCR Ecosystem

Hello GPCR people! Check out our GPCR roundup now, and be the first to read! This week's highlight: Congrats to our partner GPCR Therapeutics, on their expansion into fibrosis with their new research. Save the dates: November 2 - 4: We're sponsoring the GPCR Retreat and would love to meet you there! Join the waitlist by emailing gpcrretreat@uottawa.ca. Submit a logo design by Nov 1st on the Logo Contest page. No registration is needed to submit your logo design. Subscribe now to Dr. GPCR Newsletter to get more info! Check out the weekly Classified GPCR News from October 2nd to 8th, 2023. 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 Development, synthesis and evaluation of novel fluorescent Endothelin-B receptor probes GPCRs in Cardiology, Endocrinology, and Taste GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals GPCRs in Neuroscience Involvement of a silkworm D2-like dopamine receptor in the promotion of feeding and related behaviors Methods & Updates in GPCR Research Functional GPCR expression in eukaryotic LEXSY system Structural and Molecular Insights into GPCR Function Interplay of Cholesterol and Actin in Neurotransmitter GPCR Signaling: Insights from Chronic Cholesterol Depletion Using Statin Side-Chain Dynamics of the α1B -Adrenergic Receptor determined by NMR via Methyl Relaxation Structural determinants of sphingosine-1-phosphate receptor selectivity Industry News Sosei Heptares and Verily Nominate First G-protein-coupled receptor Target for Therapeutic Development DKK 25 million to development of databases supporting medical research ‘Define your own success’: Duke leaders talk success, failure at symposium honoring Nobel Laureate Robert Lefkowitz Integral Molecular Secures Nearly $900K in NIH Funding to Discover Antibodies Against Difficult and Conserved Protein Targets GPCR Therapeutics Expands Pipeline into Fibrosis with a Combination Approach Targeting LPA1 GPCR Events, Meetings, and Webinars October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW Senior Scientist, In vitro pharmacology - Crinetics Pharmaceuticals NEW Senior Director, In vitro pharmacology - Crinetics Pharmaceuticals In vivo Antibody Discovery Research Scientist In Vitro Biologist/Molecular Pharmacologist Senior Vice President, Oncology Clinical Research Scientist (level I or II) Research Fellow Research Technician II - Surgery Post-Doc Research Associate Research Technician Explore Dr. GPCR Ecosystem

Hello GPCR enthusiasts! Join us for our weekly GPCR round-up. This week's highlights: Drs. Michel Bouvier, J Silvio Gutkind, and team found that Gαs is essential for GRK selectivity and gene regulation by β2-adrenergic receptor. Dr. Matthew Eddy and lab research on GPCR signaling mechanisms using NMR spectroscopy with labeled receptors. Save the dates: November 2 - 4: We are excited to announce that we are sponsors of the GPCR Retreat and would love to meet you there! Unfortunately, registration has closed, but you can still join the waitlist by emailing gpcrretreat@uottawa.ca. In addition, we are currently seeking a new logo for this renowned event. You can submit your logo design by November 1st, and registration is unnecessary to participate. You can find all the necessary information on the Logo Contest page. Did you know that as a premium member, you enjoy exclusive access to recorded talks from our Dr. GPCR Symposia? Also, If you attended any of the talks, we'd truly value your feedback through our survey. Subscribe now to gain access to exclusive insights from Dr. GPCR Newsletter! And now, without further ado, dive into the latest Classified GPCR News from September 25th to October 1st, 2023. GPCR Activation and Signaling The non-nutritive sweetener sucralose increases β-arrestin signaling at the constitutively active orphan G protein-coupled receptor GPR52 β-Arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR Gαs is dispensable for β-arrestin coupling but dictates GRK selectivity and is predominant for gene expression regulation by β2-adrenergic receptor Allosteric modulation of the fish taste receptor type 1 (T1R) family by the extracellular chloride ion Illuminating GPCR signaling mechanisms by NMR spectroscopy with stable-isotope labeled receptors GPCR Binders, Drugs, and more Orthosteric ligand selectivity and allosteric probe dependence at Hydroxycarboxylic acid receptor HCAR2 Antipsychotic displays dual GPCR binding mode GPCRs in Cardiology, Endocrinology, and Taste An extracellular glucose sensor for substrate-dependent secretion and display of cellulose-degrading enzymes Functional Water Channels Within the TSH Receptor - a new paradigm for TSH action with disease implications GPCRs in Oncology and Immunology LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration Respiratory infections predominate after day 100 following B-cell maturation antigen-directed CAR T-cell therapy SSTR2 positively associates with EGFR and predicts poor prognosis in nasopharyngeal carcinoma Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions Methods & Updates in GPCR Research Polyphosphate uses mTOR, pyrophosphate, and Rho GTPase components to potentiate bacterial survival in Dictyostelium Reviews, GPCRs, and more Network pharmacology -based study on the mechanism of traditional Chinese medicine in the treatment of glioblastoma multiforme Industry News Structure Therapeutics Announces Positive Results from Phase 1b Clinical Study of Oral GLP-1 Receptor Agonist GSBR-1290 and Provides Program Update Septerna sells GPCR program to Vertex for $48 million Merck KGgA collaborates with Exscientia plc in deal worth up to $674M 2023 Half-Year Financial Results and Exciting Developments at Aelis Farma Ion Channel Drug Developer Maxion Therapeutics Appoints Eva-Lotta Allan as Chair of its Board of Directors Novo Nordisk and Evotec collaborate to launch LAB eN², a translational drug discovery accelerator, to address innovation gap in cardiometabolic diseases GPCR Events, Meetings, and Webinars October 2 - 3, 2023 | Celebrating Robert J. Lefkowitz's Career at Duke October 3, 2023, | FREE Seminar: Changing paradigm on Therapeutics targeting Membrane Proteins: from antigen production to candidate validation October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW In vivo Antibody Discovery Research Scientist NEW In Vitro Biologist/Molecular Pharmacologist Senior Vice President, Oncology Clinical Research Scientist (level I or II) Research Fellow Research Technician II - Surgery Post-Doc Research Associate Research Technician Explore Dr. GPCR Ecosystem

Hi readers! Take a few minutes and dive into our GPCR coverage! Our recent Dr. GPCR Symposium about 'GPCRs as Therapeutic Modalities' rocked it! A huge thank you to our amazing speakers and everyone who showed up. If you couldn't make it, no sweat – our premium members can always go back and watch the recorded talks at any time here. For attendees, kindly spare a moment to complete our survey. Save the dates: November 2 - 4: We're proud sponsors of the GPCR Retreat and can't wait to meet you there! Registration is now closed, but you can join the waitlist by emailing gpcrretreat@uottawa.ca. If you're already registered, kindly use the provided form to submit your poster abstracts. Short talk selections will be announced soon. Abstract submissions close on October 2nd. We are also looking for a new logo for this iconic event. Submit your logo design by November 1st. You don't need to be registered to participate. All information is available on the Logo Contest page. Access exclusive insights by subscribing to the Dr. GPCR Newsletter! Dive into the Classified GPCR News from September 18th to 24th, 2023. GPCR Activation and Signaling Rules and mechanisms governing G protein coupling selectivity of GPCRs Location-biased activation of the proton-sensor GPR65 is uncoupled from receptor trafficking GPCR Binders, Drugs, and more An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism GPCRs in Cardiology, Endocrinology, and Taste Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype Mesenchymal stromal cell secretory molecules improve the functional survival of human islets AT2 receptor agonist LP2 restores respiratory function in a rat model of bleomycin-induced lung remodelling GPCRs in Neuroscience Photoactivatable Agonist-Antagonist Pair as a Tool for Precise Spatiotemporal Control of Serotonin Receptor 2C Signaling GPCRs in Oncology and Immunology CaaX-motif-adjacent residues influence G protein gamma (Gγ) prenylation under suboptimal conditions Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody Activation of PI3K/Akt pathway by G protein-coupled receptor 37 promotes resistance to cisplatin-induced apoptosis in non-small cell lung cancer Methods & Updates in GPCR Research Target immobilization on glass microfiber membranes as a label-free strategy for hit identification Reviews, GPCRs, and more The discovery, structure, and function of 5-HTR1E serotonin receptor Structural and Molecular Insights into GPCR Function Cryo-EM structures of human GPR34 enable the identification of selective antagonists Industry News Inside the FDA's Form 483 findings at Novo Nordisk's North Carolina semaglutide plant Excellerate Bioscience Announces Site Relocation AI can help to speed up drug discovery — but only if we give it the right data Inversago Pharma divulges new cannabinoid CB1 receptor antagonists BenevolentAI, Exscientia on the comeback trail after securing separate AI drug discovery deals with Merck KGaA Pfizer’s Vydura recommended by NICE for acute migraines Addex mGlu2 NAM Cognition Program Receives €4 Million Grant Confo Therapeutics Appoints Stephen Dowd As Chief Business Officer Call for GPCR Papers opnMe GPCR Route 66+ project. Deadline September 27, 2023 GPCR Events, Meetings, and Webinars October 2 - 3, 2023 | Celebrating Robert J. Lefkowitz's Career at Duke October 3, 2023, | FREE Seminar: Changing paradigm on Therapeutics targeting Membrane Proteins: from antigen production to candidate validation October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW Senior Vice President, Oncology Clinical Research NEW Scientist (level I or II) NEW Research Fellow Research Technician II - Surgery Post-Doc Research Associate Research Technician Senior Research Associate, In Vitro Pharmacology - Crinetics Pharmaceuticals Postdoc In Cell Biology Of Protein Trafficking Postdoctoral Fellow Explore Dr. GPCR Ecosystem

Nanobodies (Nbs), known as variable antigen-binding (VHH) domain or single-domain antibodies, are small antigen-binding fragments. Nbs typically consist of a single polypeptide chain which contains the antigen-binding site and the effector functions. They are derived from the heavy-chain antibodies found in camelids (such as camels and llamas) and their small size, about one-tenth the size of conventional antibodies, makes them highly versatile and easy to manipulate for various applications1,2. Nbs are useful tools for dynamic biological systems; they have been used to crystallize flexible membrane proteins, transient multiprotein assemblies, and individual molecules of complex proteins. They have also been used as biosensors to monitor conformational changes of GPCRs in living cells. All the above lightly represent the potential applications of Nbs to facilitate the development of more selective drugs capable of modulating specific signaling pathways, improving therapeutic activity, and minimizing side effects1,2. Some important characteristics of Nbs are: Small size and solubility: Their small size and soluble nature make them ideal building blocks for generating multivalent or multispecific constructs. Tailorable half-life: Nanobodies can extend their half-life through PEGylation or fusion to serum albumin. This allows for tailoring the half-life of nanobodies to increase their therapeutic window depending on the clinical indication. Binding to cryptic epitopes and conformational selection: Nanobodies have a unique shape that allows them to bind to cavities or clefts on the surfaces of proteins that are inaccessible to conventional antibodies. They can recognize cryptic epitopes often composed of discontinuous amino acid segments and occur only within the fully native protein. Nbs can stabilize specific conformations of proteins, including unstable structural intermediates and substates of conformationally complex proteins. Generation, selection and functional expression: Nanobodies can be obtained by immunizing a camelid and cloning the variable VHH gene repertoire. Combinatorial biology methods such as phage display, yeast display, and ribosome display can be used to select nanobodies with desired functions. Most Nbs can be functionally expressed as genetically encoded intrabodies within a eukaryotic cell. This allows for correlating structural or dynamic features observed in vitro with functional observations from living cells. Potential for protein crystallization: Nanobodies can be used to stabilize the protomers of larger protein assemblies and increase the total amount of structured polypeptide. This provides a better starting point for the crystallization of intrinsically unfolded proteins. Some Nbs that have been use for GPCR research are: Nb80: This nanobody stabilized an active-state conformation of the β2 adrenergic receptor (β2AR)3. Nb6B9: This is an affinity-matured nanobody derived from Nb80. It has slower dissociation kinetics at the β2AR and was used to capture the structure of β2AR bound to adrenaline3. Nb35: This nanobody selectively binds to the β2AR·Gs complex and prevents the dissociation of the nucleotide-free complex by the nonhydrolyzable GTP analog GTPγS4. Nb37: Similar to Nb35, this nanobody selectively binds to the β2AR·Gs complex and helps reveal the conformational flexibility of the Gαs α-helical domain. Nb9-8: This nanobody was identified for the M2 muscarinic receptor (M2R) and increased the affinity of agonists. Nb39: This nanobody was identified for the μ-opioid receptor (μOR) and also increased the affinity of agonists4. Nb7: This nanobody improves the diffraction quality of the constitutively active GPCR US28·CX3CL1 complex5. This year Arum Wu et al. reported a library of Nbs to study the allosteric modulation of the rhodopsin receptor activation and investigate the role of specific regions in the switching between different conformational states. This Nbs binds to the extracellular surface of the Rhodopsin receptor and stabilizes the photo-activated receptor in a ground-state-like. The findings of this study showed that the Nb2 binding to native rhodopsin stabilizes its conformation, protects the Schiff base, and prevents protein degradation, potentially offering therapeutic benefits for retinal diseases6. To know more about this report check this link. References: Jin, B. K., Odongo, S., Radwanska, M., & Magez, S. (2023). Nanobodies: A Review of Generation, Diagnostics and Therapeutics. International journal of molecular sciences, 24(6), 5994. https://doi.org/10.3390/ijms24065994 Manglik, A., Kobilka, B. K., & Steyaert, J. (2017). Nanobodies to Study G Protein-Coupled Receptor Structure and Function. Annual review of pharmacology and toxicology, 57, 19–37. https://doi.org/10.1146/annurev-pharmtox-010716-104710 Rasmussen, S. G., Choi, H. J., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., Devree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. H., Pautsch, A., Steyaert, J., Weis, W. I., & Kobilka, B. K. (2011). Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. Nature, 469(7329), 175–180. https://doi.org/10.1038/nature09648 Kruse, A. C., Ring, A. M., Manglik, A., Hu, J., Hu, K., Eitel, K., Hübner, H., Pardon, E., Valant, C., Sexton, P. M., Christopoulos, A., Felder, C. C., Gmeiner, P., Steyaert, J., Weis, W. I., Garcia, K. C., Wess, J., & Kobilka, B. K. (2013). Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature, 504(7478), 101–106. https://doi.org/10.1038/nature12735 Burg, J. S., Ingram, J. R., Venkatakrishnan, A. J., Jude, K. M., Dukkipati, A., Feinberg, E. N., Angelini, A., Waghray, D., Dror, R. O., Ploegh, H. L., & Garcia, K. C. (2015). Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor. Science (New York, N.Y.), 347(6226), 1113–1117. https://doi.org/10.1126/science.aaa5026 Wu, A., Salom, D., Hong, J. D., Tworak, A., Watanabe, K., Pardon, E., Steyaert, J., Kandori, H., Katayama, K., Kiser, P. D., & Palczewski, K. (2023). Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain. Nature communications, 14(1), 5209. https://doi.org/10.1038/s41467-023-40911-9

Hello GPCR people! Check out our GPCR roundup now, and be the first to read! This week's highlights: Celebrating Dr. Robert Lefkowitz on his 50 years at Duke. Congratulations. Dr. Graeme Milligan and their colleagues research on Pro-phagocytic function and structural basis of GPR84 signaling. Congrats to Dr. Kevin Wright on his new position as Director of Targeted and Immuno-oncology at GPCR Therapeutics, our partner. Mark your calendars for the following events: September 22- TOMORROW: Attend this Friday's Dr. GPCR Symposium on 'GPCRs as Therapeutic Modalities' with Richa Tyagi, Dr. Terry Kenakin, Dr. Oliver Hartley, Dr. Pierre Eftekhari, Dr. Lauren Slosky, Dr. Christel Menet, Dr. Ben Myers and Dr. Niña Caculitan. Since you are reading this newsletter, you only have to click on the event page to join us. November 2 - 4: We are sponsoring the GPCR Retreat and look forward to seeing you there! Registrations are closed but you can send an email to gpcrretreat@uottawa.ca to be added to the waitlist. If you have registered, please submit poster abstracts through this form and the short talk selections will be made. Abstract submissions close on October 2nd. Subscribe to the Dr. GPCR Newsletter and receive valuable insights! Please take a look at the weekly Classified GPCR News from September 11th to 17th, 2023. GPCR Activation and Signaling Characterization of the real-time internalization of nine GPCRs reveals distinct dependence on arrestins and G proteins GPCR Binders, Drugs, and more Studying allosteric regulation of chemokines and antagonists using a nanoscale hCCR3 receptor sensor GPCRs in Oncology and Immunology Phase 1/2 study of sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML miR-19a may function as a biomarker of oral squamous cell carcinoma (OSCC) by regulating the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population Identification of S1PR4 as an immune modulator for favorable prognosis in HNSCC through machine learning Prediction of survival and immunotherapy response by the combined classifier of G protein-coupled receptors and tumor microenvironment in melanoma Methods & Updates in GPCR Research Genetic atlas of hygro-and thermosensory cells in the vinegar fly Drosophila melanogaster Structural and Molecular Insights into GPCR Function Pro-phagocytic function and structural basis of GPR84 signaling Structural diversity of leukotriene G-protein coupled receptors Industry News Duke University Celebrates Nobel Prize Winner Robert Lefkowitz’s 50 Years of Scientific Discovery Novo Nordisk Foundation Grants Fuel Exciting GPCR and Signaling Protein Research Tools First-In-Class Drug Shows Potential for Treatment of Cannabis Use Disorder Reproducibility of Tanso Biosciences' GPCR Assay Septerna: making another run on GPCRs Addex Mglu2 Nam Cognition Program Receives €4 Million Grant Dr. Kevin Wright Joins GPCR Therapeutics as Director of Targeted and Immuno-oncology Sosei Heptares Adds World-leading Expertise to its Scientific Advisory Board Call for GPCR Papers opnMe GPCR Route 66+ project. Deadline September 27, 2023 GPCR Events, Meetings, and Webinars September 25 - 28, 2023 | Discovery On Target September 27 - 28, 2023 | Training Seminar "The Renaissance in GPCRs as Drug Targets: Allosteric Function and Biased Signaling" at the DOT NEW October 2 - 3, 2023 | Celebrating Robert J. Lefkowitz's Career at Duke October 3, 2023, | FREE Seminar: Changing paradigm on Therapeutics targeting Membrane Proteins: from antigen production to candidate validation October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW Research Technician II - Surgery NEW Post-Doc Research Associate NEW Research Technician Senior Research Associate, In Vitro Pharmacology - Crinetics Pharmaceuticals Postdoc In Cell Biology Of Protein Trafficking Postdoctoral Fellow Researcher / Senior Researcher in Structural Biology Research Specialist Explore Dr. GPCR Ecosystem

Good day readers! Welcome to our latest GPCR updates. This week's highlights: Dr. Yamina Berchiche, Founder and Director of Dr. GPCR, was featured as Superluminal Medicines Launches to Drug Protein Conformations in a Flash. Our partner, Domain Therapeutics, will attend the SACHS 23rd annual biotech event in Europe. Dr. Gregory Tall and team's study on GPR114/ADGRG5, activated by tethered-peptide-agonist, a cleaved adhesion GPCR. Dr. Christopher Langmead and colleagues' work on the 5-HT2C receptor as a therapeutic target for substance use disorders. Save these dates: September 22: Join us for the Dr. GPCR Symposium on ''GPCRs as Therapeutic Modalities' Share your project with a 1-minute abstract video with this form. November 2 - 4: The GPCR Retreat is approaching and we are thrilled to be sponsors! Submit poster abstracts here; short talks will be selected from Abstracts. Abstract submissions close on October 2, and final registration ends on September 21. Subscribe to the Dr. GPCR Newsletter for more insights! Now, explore the Classified GPCR News from September 4th to 10th, 2023. Adhesion GPCRs GPR114/ADGRG5 is activated by its tethered-peptide-agonist because it is a cleaved adhesion GPCR Latrophilin, an adhesion GPCR with galactose-binding lectin domain involved in the innate immune response of Tribolium castaneum GPCR Activation and Signaling Biased allosteric activation of ketone body receptor HCAR2 suppresses inflammation GPCR Binders, Drugs, and more Saturated Cannabinoids: Update on Synthesis Strategies and Biological Studies of These Emerging Cannabinoid Analogs GPCRs in Neuroscience Serotonin signaling regulates actomyosin contractility during morphogenesis in evolutionarily divergent lineages GPCRs in Oncology and Immunology [1,2,4]Triazolo[1,5-c]pyrimidines as Tools to Investigate A3 Adenosine Receptors in Cancer Cell Lines Severity of neurological long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors Methods & Updates in GPCR Research Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats Reviews, GPCRs, and more Understanding class B GPCR agonist binding Structural and Molecular Insights into GPCR Function Structure and Molecular Mechanism of Signaling for the Glucagon-like Peptide-1 Receptor Bound to Gs Protein and Exendin-P5 Biased Agonist Molecular and structural insights into the 5-HT2C receptor as a therapeutic target for substance use disorders Industry News Crinetics’ Once-Daily Oral Paltusotine Achieved The Primary And All Secondary Endpoints In The Phase 3 Pathfndr-1 Study Evaluating Treatment Of Patients With Acromegaly Crinetics Announces September 2023 Inducement Grants Click Therapeutics teams up with addiction treatment maker Indivior to make digital therapeutics for substance use disorders Superluminal Medicines Launches to Drug Protein Conformations in a Flash Andrew Hopkins, Exscientia's CEO, Recognized in TIME Magazine's for Pioneering AI-Driven Drug Discovery Domain Therapeutics CEO Pascal Neuville to Discuss Game-Changing GPCR-Targeting Immunotherapies at Sachs Associates' Biotech Forum Celtarys Research and G-CLIPS join forces to revolutionize transmembrane proteins characterization in drug discovery Confo Therapeutics Appoints Stephen Dowd As Chief Business Officer Septerna Announces Novel GPCR-targeted Program Acquired by Vertex Call for GPCR Papers opnMe GPCR Route 66+ project. Deadline September 27, 2023 GPCR Events, Meetings, and Webinars NEW September 21, 2023 | Breaking Through the Barriers: Unlocking the Future of Ion Channel Drug Discovery with Cryo-EM September 25 - 28, 2023 | Discovery On Target September 27 - 28, 2023 | Training Seminar "The Renaissance in GPCRs as Drug Targets: Allosteric Function and Biased Signaling" at the DOT October 3, 2023 | FREE Seminar: Changing paradigm on Therapeutics targeting Membrane Proteins: from antigen production to candidate validation October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW Senior Research Associate, In Vitro Pharmacology - Crinetics Pharmaceuticals NEW Postdoc In Cell Biology Of Protein Trafficking NEW Postdoctoral Fellow Researcher / Senior Researcher in Structural Biology Research Specialist Science Research Writer Postdoctoral Fellow Research Laboratory Specialist Associate Explore Dr. GPCR Ecosystem

Hello, hello! Stay informed with our GPCR roundup. Mark your calendars for these important events: September 22: Save the date for the Dr. GPCR Symposium on 'GPCRs as Therapeutic Modalities' Showcase your project with a 1-minute abstract video using this form. Our poster session is now an engaging Kumospace discussion. November 2 - 4: Get ready for the upcoming GPCR Retreat! We are excited to share that we are sponsors of this event. You can submit your poster abstracts using this form and short talks will be selected from abstracts. Please remember that the early-bird registration deadline ends tomorrow, the abstract submissions deadline is October 2nd, and the final registration cutoff is September 21st. Subscribe to Dr. GPCR Newsletter to gain access to further insights! Don’t forget to check out the weekly Classified GPCR News from August 28th to September 3rd, 2023. GPCR Activation and Signaling Cell death signaling in Anopheles gambiae initiated by Bacillus thuringiensis Cry4B toxin involves Na+/K+ ATPase GPCR Promiscuity Reshapes Islet Physiology TGR5 supresses cGAS/STING pathway by inhibiting GRP75-mediated endoplasmic reticulum-mitochondrial coupling in diabetic retinopathy GPCR Binders, Drugs, and more The Leu/Val6.51 Side Chain of Cannabinoid Receptors Regulates the Binding Mode of the Alkyl Chain of Δ9-Tetrahydrocannabinol GPCRs in Cardiology, Endocrinology, and Taste Cholecystokinin-A Signaling Regulates Automaticity of Pacemaker Cardiomyocytes Dopamine Receptor D1 Is Exempt from Transforming Growth Factor β-Mediated Antifibrotic G Protein-Coupled Receptor Landscape Tampering in Lung Fibroblasts GPCRs in Neuroscience System-wide mapping of peptide-GPCR interactions in C. elegans GPCR interactions involving metabotropic glutamate receptors and their relevance to the pathophysiology and treatment of CNS disorders GPCRs in Oncology and Immunology From outside to inside and back again: the lysophosphatidic acid-CCN axis in signal transduction NPFF stimulates human ovarian cancer cell invasion by upregulating MMP-9 via ERK1/2 signaling CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration Methods & Updates in GPCR Research 3DDPDs: describing protein dynamics for proteochemometric bioactivity prediction. A case for (mutant) G protein-coupled receptors Reviews, GPCRs, and more RGS2 and female common diseases: a guard of women's health β-Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives COVID-19, G protein-coupled receptor, and renin-angiotensin system autoantibodies: Systematic review and meta-analysis Structural and Molecular Insights into GPCR Function Analysis of the Dynamics of the Human Growth Hormone Secretagogue Receptor Reveals Insights into the Energy Landscape of the Molecule Focused classifications and refinements in high-resolution single particle cryo-EM analysis Structure-based drug discovery of a corticotropin-releasing hormone receptor 1 antagonist using an X-ray free-electron laser Structural insight into the selective agonist ST1936 binding of serotonin receptor 5-HT6 Industry News Septerna Bolsters Leadership Team as the Company Advances its Multi-Product Pipeline Toward Clinical Studies Confo Therapeutics Appoints Dieter Weinand, Former CEO Of Bayer Pharmaceuticals, As Independent Chairman Addex Adx71149 Phase 2 Epilepsy Study Expected To Readout Data In Q2 2024 Addex Announces Participation In The H.C. Wainwright 25th Annual Global Investment Conference X4 Pharmaceuticals to Participate in the Morgan Stanley 21st Annual Global Healthcare Conference CEO Raymond Stevens to Speak at STAT Future Summit on Obesity Therapeutics Call for GPCR Papers NEW opnMe GPCR Route 66+ project. Deadline September 27, 2023 GPCR Events, Meetings, and Webinars September 25 - 28, 2023 | Discovery On Target September 27 - 28, 2023 | Training Seminar "The Renaissance in GPCRs as Drug Targets: Allosteric Function and Biased Signaling" at the DOT NEW October 3, 2023 | FREE Seminar: Changing paradigm on Therapeutics targeting Membrane Proteins: from antigen production to candidate validation October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference 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 - 4, 2024 | Chemotactic Cytokines GPCR Jobs Researcher / Senior Researcher in Structural Biology Research Specialist Science Research Writer Postdoctoral Fellow Research Laboratory Specialist Associate Postdoc Research Associate Director, Regulatory Affairs Research Scientist/Senior Scientist I - Molecular Pharmacology Explore Dr. GPCR Ecosystem