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September 2022 Ginsenoside Rg5 allosterically interacts with P2RY12 and ameliorates deep venous thrombosis

October 2022 Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations "Allosteric modulators protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation modulators at the receptor-lipid interface. The allosteric cavities are detectable in various membrane compositions.

October 2022 Membrane Lipids Are an Integral Part of Transmembrane Allosteric Sites in GPCRs: A Case Study of Cannabinoid CB1 Receptor Bound to a Negative Allosteric Modulator, ORG27569, and Analogs "A growing number of G-protein-coupled receptor (GPCR) structures reveal novel transmembrane lipid-exposed allosteric

A MOR-positive allosteric modulator (BMS-986122) selectively enhances opioid signaling  through specific

Here, we report the structure-based development of fluorescent ligands targeting the intracellular allosteric

Thal , et al., for their groundbreaking work on Positive allosteric modulation of a GPCR ternary complex 𝗿𝗲𝘀𝘂𝗹𝘁𝘀 𝗼𝗳 𝗔𝗘𝗙𝟬𝟭𝟭𝟳 𝗣𝗵𝗮𝘀𝗲 𝟮𝗯 𝗶𝗻 𝗖𝗨𝗗 Nxera Pharma’s Partner Centessa Announces Positive Senior Scientist/Staff Scientist, Computational Chemistry Postdoc in GPCR mechanosensing   Postdoctoral Position Postdoctoral research position Adhesion GPCRs Loss of cardiomyocyte-specific Adhesion G Protein Coupled allosteric modulation of a GPCR ternary complex GPCR Binders, Drugs, and more Progress on the development

Discovery and in vitro Characterization of BAY 2686013, an Allosteric Small Molecule Antagonist of the PTK7 is a positive allosteric modulator of GPR133 signaling in glioblastoma. into GPCR Function Structure-Activity Relationship Study of the High-Affinity Neuropeptide Y4 Receptor Positive Allosteric Modulator VU0506013. Scientist II DOE (Native Mass Spectrometry) Senior Vice President of Global Medical Affairs Postdoctoral Position

2026 GPCR Pharmacology AMA: Receptor Theory, Biased Signaling & Assay Interpretation The first GPCR Pharmacology AMA of 2026  at Terry’s Corner will take place on: Thursday, February 26 at 1 PM EST Dr. Kenakin will address receptor theory, assay interpretation, biased signaling, and practical drug discovery challenges — driven by questions from the community. These sessions focus on real scientific uncertainty, not rehearsed presentations. Terry’s Corner Expands to YouTube Terry’s Corner is now on YouTube. Three videos are already live, and the channel will expand regularly. The objective is straightforward: Make mechanistic pharmacology easier to access, revisit, and apply across research teams. Short conceptual breakdowns Focused receptor theory discussions Clear explanations reinforcing disciplined interpretation As the archive grows, it becomes a searchable extension of Terry’s teaching — designed for repeated exposure rather than one-time viewing. Subscribe to stay current as new videos are released: ▶️ https://www.youtube.com/@TerryPharmacologyCorner New White Paper on GPCR Biased Signaling Terry Kenakin, Ph.D., Professor of Pharmacology at the University of North Carolina School of Medicine, has authored a new white paper in collaboration with Eurofins DiscoverX: Assess GPCR Biased Signaling of Agonists Using Functional Cell-Based Assays The paper explores: Detection and quantification of signaling bias Influence of biased signaling on therapeutic profiles Application of quantitative tools such as transduction coefficients (log(τ/KA) or log(max/EC50)) Systematic comparison of biased agonists using modern functional assays For scientists working in GPCR programs, this connects functional assay data directly to translational decision-making — moving beyond descriptive bias claims toward quantitative rigor. Access the white paper here Why Terry’s Pharmacology Corner Mechanistic understanding evolves. What appears settled under one experimental condition may require refinement under another. What seems definitive during early screening can shift as assay systems, receptor expression levels, or kinetics change. Pharmacology does not drift because data are missing. It drifts when interpretation becomes casual. Terry’s Pharmacology Corner provides a structured environment to maintain interpretive discipline: Weekly advanced pharmacology lectures Monthly live AMAs for real-time scientific discussion A continually expanding on-demand archive Sustained exposure to quantitative receptor theory and mechanistic reasoning The value lies not in a single explanation, but in preserving rigor as programs mature. Forty years of pharmacological expertise — organized into a year-round framework for serious GPCR scientists. Stay in the Know If you want updates on future AMAs, new YouTube releases, white papers, and ongoing pharmacology insights, join Terry Kenakin’s Brief . Concise. Focused. Mechanistic. 👉 Sign up here Continue the Work Live sessions are one layer. Sustained exposure is where judgment sharpens. If you want structured, year-round access to Terry’s full library — including advanced lectures, archived AMAs, and quantitative pharmacology deep dives: 👉 Access Terry’s Corner Free for 7 Days Strengthen Your Mechanistic Thinking

Ways Schild plots reveal hidden complexities like allosterism and receptor heterogeneity. Slopes <1  may reveal allosteric modulation , where the antagonist binds at a secondary site. When these same molecules act as antagonists, their curves shift not only in position but also in shape The model’s flexibility accommodates both agonism and antagonism as long as the analysis targets equilibrium Allosteric vs. orthosteric inhibition , distinguishable by the plateauing of effect.

Most GPCR programs don’t fail because of weak molecules—they fail because biology behaves differently than the assay implied. This week’s feature goes straight to the foundation: how system-level GPCR thinking  protects discovery teams from the costly misinterpretations that derail programs. If your work touches GPCR pharmacology, these insights aren’t optional—they’re essential. Breakthroughs this week: Eli Lilly cuts Zepbound prices; GNAI1 missense mutation study; rapid Gαs endosomal translocation. 🔍 This Week in Premium: Sneak Peek Industry insights:  Lilly cuts Zepbound prices; Lilly hits $1T valuation; Novo advances amycretin. Upcoming events:  Adhesion GPCR Workshop; GRC—Transporters, Ion Channels & GPCRs; MPGPCR Joint Satellite Meeting. Career opportunities:  Senior/Principal Scientist—GPCR Pharmacology; Principal Scientist—In Vitro Pharmacology; Research Associate—Biologics Discovery. Must-read publications:  Gαi1 neurodevelopmental mutation; Gαs endosomal signaling; primary cilia as transduction hubs. Terry’s Corner: GPCR Pharmacology Insights That Prevent Real Drug Discovery Failures Discovery collapses when teams assume stable, linear, receptor-to-response relationships. Dr. Kenakin’s AMA made the central point unmistakable: GPCR systems constantly reshape ligand behavior through coupling efficiency, receptor density, local signaling architecture, and physiological feedback loops. This is where system-level GPCR thinking  becomes a competitive advantage—long before a molecule reaches animals or patients. When you see the distortions baked into the system, you interpret your data differently and protect your program from preventable failures. What You’ll Gain Spot false confidence early  → Sensitivity differences can turn full agonists into partials or even antagonists depending on system load. Avoid misleading mechanistic labels  → NAMs, PAMs, and biased agonists behave in system-dependent ways that single assays cannot reveal. Translate potency and efficacy realistically  → Recognize when deviations reflect biology rather than compound failure. Premium Members get 67% discount when they join Terry’s Corner in 2025 Sharpen your interpretation skills ➤ Dr. GPCR Podcast: Chemical Probes for GPCR Imaging with Dr. Johannes Broichhagen Reliable imaging tools change how researchers see receptor behavior. In this episode, Dr. Johannes Broichhagen explains how next-generation fluorescent probes—designed with precise synthetic logic—enable deeper insight into GPCR internalization, trafficking, and surface organization. His work shows why chemical design can outperform antibodies and how rigorous assay validation bridges chemistry and biology effectively. What You’ll Learn Why peptide–fluorophore probes succeed where antibodies fail How parallel synthesis& testing accelerates probe optimization How surface-exposed receptor pools reshape interpretations of trafficking Listen to the episode ➤ High-Content Screening for GPCR Programs: Overcoming Assay Limitations with Fluorescent Ligands High-content screening (HCS) is now indispensable for GPCR workflows—especially when spatial context, trafficking behavior, and live-cell kinetics matter. But HCS only works when assays are built with rigor and powered by the right fluorescent ligands. This feature from Celtarys Research outlines how to structure an HCS workflow that avoids batch effects, imaging artifacts, and variability while delivering reliable, mechanistic data. What You’ll Learn Why traditional radioligand assays miss critical spatial and kinetic signals Five phases of a robust, reproducible HCS pipeline How fluorescent ligands strengthen specificity, relevance, and assay confidence Read the full HCS feature ➤ Why System-Level GPCR Thinking Changes Data Interpretation And How Dr. GPCR Premium Membership Gives You an Edge Premium gives GPCR scientists and biotech teams a single, trusted source of weekly insight that cuts through noise. Members access deep-dive lectures, expert frameworks, curated jobs, upcoming events, and classified more. It’s a system-aware resource built for researchers who need clarity fast—reinforcing system-level GPCR thinking  every week so your interpretations stay sharp and aligned with real biology. FAQ 🔹 What’s included? Weekly research, careers, and industry intelligence; GPCR University; 200+ expert talks; networking; and member-only discounts. 🔹 Who is it for? Researchers, pharmacologists, biotech teams, and decision-makers who rely on accurate, efficient, interpretation-first information. 🔹 Why now? GPCR innovation is accelerating—and misinterpretation compounds quickly. Staying informed today prevents the delays others won’t see coming. Don’t Fall Behind—Access the Edge You Need Already a Premium Member? 👉 Access this week’s full Premium Edition here ➤ What Members Say "I am a convert! I will keep Dr. GPCR and the offered resources in my work sphere." Help us reach more scientists by providing quick rating on Spotify or Apple Podcasts — and a YouTube subscribe. Spotify: https://open.spotify.com/show/1KQHbC2qhkRIrdgBDtiQVF Apple Podcasts: https://podcasts.apple.com/us/podcast/dr-gpcr-podcast/id1514231064 YouTube: https://www.youtube.com/@DrGPCR Want to support Dr. GPCR? 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development of new CB2-related pharmacological and genetic tools, including the first small molecule positive allosteric modulator of CB2 receptors, has greatly advanced our understanding of this receptor. consequence of CB2 receptor activation could correct circuit-based deficits commonly associated with positive

Addex Therapeutics (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today announced that Janssen Pharmaceuticals, Inc., ADX71149 is a selective metabotropic glutamate type 2 (mGlu2) receptor positive allosteric modulator

Nanobody binding stabilizes G-protein-coupled receptors (GPCR) in a fully active state and modulates However, the atomic-level basis for this allosteric regulation remains elusive. In particular, we identify unique allosteric signal transmission mechanisms between the Nb80-binding site and the extracellular domains in conformations modulated by a full agonist, BI167107, and a G-protein-biased

Breakthroughs this week: Structure-based discovery of positive allosteric modulators of the A1 adenosine opportunities:  Principal Scientist - In Vitro Pharmacology; Senior Scientist, Molecular Pharmacology; PhD position Prevent wasted cycles:  Avoid costly delays caused by false positives from static affinity readouts. modulators to computational targeting—will take shape. Identify emerging targets:  Allosteric modulators, biased ligands, and kinetic frameworks will dominate

Allosteric Modulation and the Microcircuit Model of GPCR Pharmacology Understanding GPCRs as allosteric Orthosteric ligands engage the primary binding site; allosteric modulators bind elsewhere on the receptor Allosteric modulation  can enhance or suppress receptor signaling (positive or negative allosteric modulators Viruses including HIV and SARS-CoV-2 exploit or modulate GPCR signaling to facilitate cell entry, immune Allosteric modulators, which do not compete directly at the orthosteric site, can be missed entirely

modulators of the glucagon subfamily of GPCRs  Let’s dive into the   Classified GPCR News  from August 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 Postdoctoral research position Senior or Lead Researcher   Senior Scientist, Cryo-Electron Microscopy

Get Yearly Access On-Demand Now — Free 7 Day Trial ➤ DrGPCR Podcast: Jens Carlsson on Predictive Modeling Jens Carlsson shares how structure-based design, molecular dynamics, and smart collaboration turn models Ideal for scientists who want modeling to guide experiments, not just narrate them. Bridge the aisle —modelers × experimentalists for faster iteration. Listen to the episode ➤ Why Dr.

receptors approved for treating dementia, we provide insights into some novel strategies, including allosterism

Terry Kenakin reframes GPCRs as dynamic, allosteric sensors—far from static binding sites. Position your research for maximum visibility.   It’s the 20th anniversary—and the spotlight is squarely on kinetic modeling, allosteric frameworks, and Terry Kenakin on “The Kinetics of Allostery: The Added Benefits of Allosteric Function.” Access peer insights on allosteric modulators and biased ligands.

receptors approved for treating dementia, we provide insights into some novel strategies, including allosterism

Microenvironment Industry News Addex and Indivior Extend Research Term Of Substance Use Disorder Gabab Positive Allosteric Modulator Discovery Collaboration Domain Therapeutics strengthens Scientific Advisory Board

community in Boston on April 29, and the GPCRs Drug Discovery Summit April 28-30. iPSC-Derived GPCR Models Patient derived iPSC's, organoid systems, and biosensor-based assays introduce models that better preserve An allosteric molecule works in concert with natural signaling, producing a fundamentally different pharmacological In this month's AMA, Terry Kenakin walks through the methods used to differentiate orthosteric from allosteric

GPCR Symposium on 'GPCRs as Therapeutic Modalities' is set for September 22nd. Neuroscience Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model Drosophila Smaug to the GPCR Smoothened and to the germline inducer Oskar Industry News Addex GABAb Positive Allosteric Modulator Program To Receive Additional Chf 2.7 Million From Indivior In Extended Substance Target - DOT (September 25 - 28, 2023) Training Seminar "The Renaissance in GPCRs as Drug Targets: Allosteric

Activate G Protein-Coupled Receptors GPCRs in Neuroscience A M1 muscarinic acetylcholine receptor-specific positive allosteric modulator VU0486846 reduces neurogliosis in female Alzheimer's mice The association of GNB5 spectroscopy Up-regulation of GPR139 in the medial septum ameliorates cognitive impairment in two mouse models

most significant groups of G-protein coupled receptor (GPCR) drug targets and also act as prototypical models ligands (i. e. aiming on two distinct OR subtypes), univalent heteromer-selective ligands and bitopic and allosteric

Alexander S Hauser GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor The cell adhesion molecule CD44 acts as a modulator of 5-HT7 receptor functions Signal profiles and spatial regulation of β-arrestin recruitment pharmacogenomics research GPCRdb in 2025: adding odorant receptors, data mapper, structure similarity search and models

Biased agonists differentially modulate the receptor conformation ensembles in Angiotensin II type 1 Therapeutic potential of allosteric modulators for the treatment of gastrointestinal motility disorders Characterization of a novel positive allosteric modulator of the α1A-Adrenergic receptor. Lipid Modulation of a Class B GPCR: Elucidating the Modulatory Role of PI(4,5)P2 Lipids. Surveying nonvisual arrestins reveals allosteric interactions between functional sites.

IM (3,3′‐methylenebis‐1H‐indole) has been identified as a positive allosteric modulator of GPR84, a metabolite

Modules: October 31st : The Eyes to See- The Importance of Pharmacologic Assays. Positive Feedback from Our Esteemed Students Past students highly recommend our programs, lauding the Postdoctoral research position GPCR Activation and Signaling Preassembly of specific Gβγ subunits at somatostatin receptors SSTR1 and SSTR3 SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor GPCR Binders, Drugs, and more Molecular glues

August 2022 "Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology. " Read more at the source #DrGPCR #GPCR #IndustryNews