Welcome aboard, GPCR Crew! Let's set sail towards exciting discoveries and groundbreaking achievements together! This Week’s Highlights: Our fearless leader, Yamina Berchiche , is gearing up to rock the mic today at the 22nd Discovery on Target ! We're sending you all the good vibes and a sprinkle of birthday magic for an epic celebration! 🚀🎉 Kilian Roßmann , Joshua Levitz , Johannes Broichhagen for their excellent work on Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology First day of class! Thrilling beginning to Principles of Pharmacology I We are excited to announce the start of our Principles of Pharmacology I course! If you snoozed on signing up for this one, fret not – there's always a spot waiting for you in Principles of Pharmacology II . Registration is open for our November class . Don’t miss this opportunity to advance your knowledge and skills in pharmacology! Registrants will learn: The powerful applications of new cellular assays to determine GPCR ligand behavior in different functional systems. Understanding real-time kinetics to predict activity and in vivo target coverage. New ligands and new GPCR behaviors that produce unique drug profiles (i.e. intracellular ligands and signaling, location bias, signaling bias). Modules: October 31st : The Eyes to See- The Importance of Pharmacologic Assays. November 7th : Drug Disposition in Physiological Tissues as a Therapeutic Variable. November 14th : The Application of GPCR Ligand Kinetics to Candidate Design. November 21st : Unconventional GPCR Ligands as Drugs. December 5th : Unique Exploitable GPCR-Ligand Behaviors for Therapeutic Benefit. *Lessons are every Thursday at 10 AM EST. 🔥 Why You Should Enroll Now: Budget-Friendly & Distinctive Educational Experience Affordable courses that maintain high-quality standards. Flexible Learning Access recorded sessions at your convenience to enhance your understanding. Our Students Highly Recommend Us! Past students praise the course content and our exceptional professors' ability to simplify the complexity of GPCR pharmacology and apply it to their research in academia and industry. Exclusive Deal for Scientists Residing and Working in Developing Nations If you live and work  in a developing country, please complete this form to enjoy complimentary access to Dr. Kenakin's upcoming course. Our goal is to ensure that education is within reach for everyone! Act Now and Become a Valued Member of our Learning Community! GPCR Event Spotlight 11th Adhesion GPCR Workshop    📍  Mexico City 📅 October 23 - 25, 2024 Get ready to ignite your passion and connect with your amazing peers to dive into the cutting-edge advancements in adhesion GPCR biology! 🌟 Get pumped up - the complete agenda is live; don't miss out HERE ! Ready to elevate your brand to new heights? Get in touch with Hello@DrGPCR.com for exciting sponsorship opportunities ! Let's take your brand to the next level together! Classified GPCR News  Let’s dive into the   Classified GPCR News from September 23rd to 29th, 2024 Industry News Superluminal Medicines Announces Formation of Scientific Advisory Board Generate:Biomedicines Announces Multi-Target Collaboration with Novartis to Discover and Develop Protein Therapeutics with Generative AI Nxera Pharma receives approval of insomnia drug in Japan Lilly and Novo Spend Billions to Expand Obesity Pipelines Beyond GLP-1s Septerna Announces Initiation of Phase 1 Clinical Trial with SEP-786, a Novel Oral Small Molecule PTH1R Agonist for the Treatment of Hypoparathyroidism Confo Therapeutics Announces Publication in Nature Communications Demonstrating First-Ever Structure of a Complex Between an Antibody-based Agonist and a Class A GPCR Regulating Hunger and Satiety OMass Therapeutics Expands Development Team with Key Appointments in US and UK and Announces the Nomination of Clinical Candidate Against MC2 Call for GPCR Papers Deadline: Nov 1, 2024. Emerging Voices in GPCR Biology in Special Issue of Molecular Pharmacology GPCR Events, Meetings, and Webinars September 30 - October 3, 2024 | 22nd Discovery on Target October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   November 25 - 27, 2024 | 1st Virtual GPCR Forum Conference November 26 - 28, 2024 | GPCRs-Targeted Drug Discovery Summit Europe July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs HIGHLIGHT Research Associate - Professor Graeme Milligan HIGHLIGHT Postdoc in Molecular Pharmacology - The Hauser Group Postdoctoral Scholar – iPSC in cardiac and endothelial cell function Protein Biochemist/Structural Biologist Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Adhesion GPCRs The G Protein-Coupled Receptor GPR56 Is an Inhibitory Checkpoint for NK Cell Migration GPCR Activation and Signaling Subcellular activation of β-adrenergic receptors using a spatially restricted antagonist GPCR Binders, Drugs, and more Deuteration as a General Strategy to Enhance Azobenzene-Based Photopharmacology GPCRs in Cardiology, Endocrinology, and Taste Rap1A Modulates Store-Operated Calcium Entry in the Lung Endothelium: A Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability GPCRs in Neuroscience Virtual screening, molecular docking and dynamics simulation studies to identify potential agonists of orphan receptor GPR78 targeting CNS disorders Predicting biological activity and design of 5-HT6 antagonists through assessment of ANN-QSAR models in the context of Alzheimer's disease GPCRs in Oncology and Immunology Aberrant hormone receptors regulate a wide spectrum of endocrine tumors G protein coupled receptor transcripts in human immune cells and platelets Methods & Updates in GPCR Research Simultaneous spectral illumination of microplates for high-throughput optogenetics and photobiology A deep learning framework combining molecular image and protein structural representations identifies candidate drugs for pain Reviews, GPCRs, and more The role of G protein-coupled receptors and their ligands in animal domestication The repertoire of G-protein-coupled receptor variations in the Japanese population 54KJPN Structural and Molecular Insights into GPCR Function Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing Reliability of AlphaFold2 Models in Virtual Drug Screening: A Focus on Selected Class A GPCRs Become a Premium Member! Get your 5-day free trial TODAY!

Course Details: When:  Thursdays at 10 AM EST Format:  Engaging Online Lectures with access to pre-read

Dear GPCR Community, Before diving into this week's news, prepare for an incredible learning journey! We’ve made some updates to the Principles of Pharmacology I & II courses, and we can’t wait for you to join us on these new dates. Here’s the refreshed schedule: Principles of Pharmacology I October 3, 10, 17, 24 Principles of Pharmacology II October 31 November 7, 14, 21 December 5 As a premium member , you’re also unlocking over 500 minutes of exclusive, expert-led content from thought leaders like Drs. Kenakin and Hoare. Don’t miss out on insightful resources like '   Applying Pharmacology to Drug Discovery ' and ' Advanced Data Analysis for GPCR Pharmacology .' We’re thrilled to have you with us on this learning journey! Courses Highlights The clock is ticking!  Don’t miss your chance to dive into the Principles of Pharmacology I & II BUNDLE . Grab your spot today and score a 25% early bird discount—exclusively for premium members. Register now and level up your expertise! Become a premium member today and enjoy a 5-day free trial. Enrollment:  Open to the Public Now! Dates:  October 3 to 24, 2024 (four sessions) Topics:  Measuring pharmacologic activity, mechanisms of action, and GPCR discovery strategies. Discount:  25% off for Premium Members—Act Fast! Dates:  October 31, November 7 - 14 -21, and December 5, 2024 (five sessions) Topics:  New cellular assays, real-time kinetics, and discovering unique GPCR behaviors. Sign up today to secure your spot! GPCR Event Spotlight    11th Adhesion GPCR Workshop    Location:  Mexico City Dates:  October 23-25, 2024 Join us  to connect with peers and explore cutting-edge adhesion GPCR biology. Don't miss the chance to boost your brand's presence at this exclusive event. Contact us at Hello@DrGPCR.com  to discover exciting sponsorship opportunities . This week's highlight includes congrats to: Madison Walker , Benjamin Myers , et al., for their research on GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade Elita Yuliantie , Arthur Christopoulos , Patrick M. Sexton , Denise Wootten , et al., for their work on Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs  Let’s dive into the   Classified GPCR News  from August 12th to 18th, 2024 Adhesion GPCRs Heterogeneity of tethered agonist signaling in adhesion G protein-coupled receptors GPCR Activation and Signaling A-Kinase-Anchoring-Protein Subtypes Differentially Regulate GPCR Signaling and Function in Human Airway Smooth Muscle GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade Allatotropin (AT) related peptides L-ATRP and D2-ATRP diastereomers activate an endogenous receptor and suppress heart rate in the Pacific abalone Haliotis discus hannai GPCR Binders, Drugs, and more Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor Isoquinoline small molecule ligands are agonists and probe-dependent allosteric modulators of the glucagon subfamily of GPCRs GPCRs in Cardiology, Endocrinology, and Taste Regulator of G-protein signaling expression in human intestinal enteroendocrine cells and potential role in satiety hormone secretion in health and obesity GPCRs in Neuroscience Light and dopamine impact two circadian neurons to promote morning wakefulness LPA3 agonist-producing Bacillus velezensis ADS024 is efficacious in multiple neuroinflammatory disease models Discovery of a potent melatonin-based inhibitor of quinone reductase-2 with neuroprotective and neurogenic properties GPCRs in Oncology and Immunology Chemoattractant receptor signaling in humoral immunity Methods & Updates in GPCR Research Probing PAC1 receptor activation across species with an engineered sensor A Multi-Angle Approach to Predict Peptide-GPCR Complexes: The N/OFQ-NOP System as a Successful AlphaFold Application Case Study Constitutive and Conditional Epitope Tagging of Endogenous G-Protein-Coupled Receptors in Drosophila Measuring G protein activation by spectrally resolved imaging fluorescence fluctuation spectroscopy Structural and Molecular Insights into GPCR Function Monitoring GPCR conformation with GFP-inspired dyes Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy Industry News Crinetics Pharmaceuticals Announces August 2024 Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Unlocking New Possibilities in GLP-1R Drug Discovery GPCR Events, Meetings, and Webinars September 5 - 6, 2024 | 4th Transatlantic ECI GPCR Symposium September 18, 2024 | FREE Webinar - The value of GPCR cell-based assays in drug discovery October 2024 | Biologics US 2024   October 2 - 4, 2024 | 9th GPCRs in Medicinal Chemistry October 17, 2024 | Unprecedented fragment-based screening using Spectral Shift for GPCRs October 23 - 25, 2024 | 11th Adhesion GPCR Workshop November 5 - 7, 2024 | 16th Annual PEGS Europe   July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Senior or Lead Researcher   Senior Scientist, Cryo-Electron Microscopy   Postdoctoral Research Associate Become a Premium Member! Get your 5-day free trial TODAY!

October 2022 β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling advanced NanoLuc/FlAsH-based biosensors reveals distinct conformational signatures of β-arrestin1 and 2 when

and subsequent activation of the G-protein heterotrimeric complex (α, β, and γ); it is at this point when Liu-Chen, and J.R. J Biol Chem, 2009. 284(27): p. 18357-67. https://pubmed.ncbi.nlm.nih.gov/19416973/ 5.

Through developing a high-resolution method, Hao Chen et al. directly visualized the fusion of vesicles Chen, X. Zhang, and L. Ma. 2008.

this has the potential to enhance GPCR subtype-selectivity, it also presents a significant challenge when modulators (NAMs), that fully or partially dampen the receptor's functional response to the ligand (Wold, Chen selectivity, which can arise from greater sequence variation in allosteric sites among receptor subtypes when This is particularly important when dealing with receptor subtypes that exhibit significant similarity substantial doses of allosteric modulators with a diminished risk of target-related toxicity (Wold, Chen

activation initiates conformational changes, exposing an intracellular cavity (Kang, Y. et al. 2015, Chen F et al. 2021, Chen, H. et al. 2022).

J Biol Chem, 2018. 293(19): p. 7466-7473. 8.      Nat Chem Biol, 2020. 16(8): p. 841-849. 10.    J Biol Chem, 2007. 282(14): p. 10576-84. 13.   

Norton Cheng and Dr.

was the most common method for predicting G protein-coupled receptor (GPCR) structures, especially when antipsychotic-like effects in rodent models, reinforcing the value of AlphaFold in drug discovery, especially when Nat Chem Biol   7 , 769-778 (2011).   https://doi.org/10.1038/nchembio.662 Diaz-Holguin, A.  

When I started studying aGPCRs, the structural conformation of the GAIN domain of ADGRL1/Lphn1 and ADGRB3 of human ADGRL3-G13, this paper reports that the stalk peptide of ADGRL3 adopts a hook conformation when Furthermore, when an alignment analysis of the Stalk peptide of the aGPCR family was performed highlighted ., Zhu, X., Wang, N., Xu, Z., Xia, R., Liang, J., Duan, Y., Yin, H., Xiong, Y., Zhang, A., Guo, C., Chen

Dysfunction of the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity Norton Cheng

When it comes to signal transduction, cellular context matters. Pharmaceuticals (Basel, Switzerland), 14(5), 439. https://doi.org/10.3390/ph14050439 Chen, K.

Want to know what’s buzzing in the world of GPCRs? 

Chem Rev, 2017. 117 (1): p. 111-138.

When comparing the CKRs structures complexes, the disulfide bridges formed between the N-loop and the agonist (maraviroc) (Tan, Zhu et al. 2013, Zheng, Han et al. 2017, Isaikina, Tsai et al. 2021, Zhang, Chen CCL15L (residues 26-92) and CCL15M (residues 27-92), while the third structure lacks a ligand (Shao, Shen conformational change of Y2917.43 tilted toward TM2, a model supported by mutagenesis experiments (Shao, Shen

Stay tuned for the latest buzz on GPCRs. This week's GPCR papers feature publications from Drs.

Experienced Pharmaceutical Executive Toshihiro Maeda as Chief Operating Officer Rhythm Pharmaceuticals and LG Chem