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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

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

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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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

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

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

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

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

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.

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

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

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.

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

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

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

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.

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

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

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

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

Terry Kenakin’s newest foundational lesson in Terry's Corner  cuts straight to it:   Why models are vital for translating lab data into clinical forecasts The 4 types of pharmacologic models (and when to use each) The truth about linear models: useful or misleading? How the Mass Action Law underpins nearly every model Future of Receptor Theory: Linkage vs. Unlock "Pharmacologic Models" now

Watch Episode 167 Today’s GPCR scientists don’t want to study one interaction, they want to model the visiting scientists are already expanding this work, bringing in computational layers  like AlphaFold to model

Predictions from modeling inform chemistry. Chemistry fuels assays. Assay data flows back into models. The cycle only works because every part is connected .   His group is trained to explain exactly what a model can predict and where its limits are. Biased signaling, allosteric binding sites, and subtype selectivity mean there is rarely a straight line He treats modeling as part of a continuum rather than a separate discipline.

October 2022 "G protein-coupled receptors (GPCRs) are important drug targets characterized by a canonical seven transmembrane (TM) helix architecture. Recent advances in X-ray crystallography and cryo-EM have resulted in a wealth of GPCR structures that have been used in drug design and formed the basis for mechanistic activation hypotheses. Here, ensemble refinement (ER) of crystallographic structures is applied to explore the impact of binding of agonists and antagonist/inverse agonists to selected structures of cannabinoid receptor 1 (CB1R), β2 adrenergic receptor (β2 AR) and A2A adenosine receptor (A2A AR). " Read more at the source #DrGPCR #GPCR #IndustryNews

receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator the activation of PTH1R and its downstream signaling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique preactivated state that permits faster activation in Moreover, RAMP2 modulates PTH1R downstream signaling in an agonist-dependent manner, most notably increasing of RAMPs in the activation and signaling of a GPCR that may provide a new venue for highly specific modulation

improved our molecular understanding of CB1 ligand interactions, selectivity, receptor activation and allosteric modulation. In this review, we describe the structural determinants for modulation of CB1 receptors by different

October 2022 Mechanism of enhanced sensitivity of mutated β-adrenergic-like octopamine receptor to amitraz in honeybee Apis mellifera: An insight from MD simulations "Background: Amitraz is one of the critical acaricides/insecticides for effective control of pest infestation of Varroa destructor mite, a devastating parasite of Apis mellifera, because of its low toxicity to honeybees. Previous assays verified that a typical G protein-coupled receptor, β-adrenergic-like octopamine receptor (Octβ2R), is the unique target of amitraz, but the honeybee Octβ2R resists to amitraz. However, the underlying molecular mechanism of the enhanced sensitivity or toxicity of amitraz to mutated honeybee Octβ2RE208V/I335T/I350V is not fully understood. Here, molecular dynamics simulations are employed to explore the implied mechanism of the enhanced sensitivity to amitraz in mutant honeybee Octβ2R." Read more at the source #DrGPCR #GPCR #IndustryNews

December 2021 Neurocrine Biosciences Announces Positive Phase 3 Data for KINECT-HD Study Evaluating Valbenazine 2022 SAN DIEGO, Dec. 7, 2021 /PRNewswire/ -- Neurocrine Biosciences (Nasdaq: NBIX) today announced positive