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Welcome GPCR Fans,   In GPCR-targeted drug discovery, precision isn’t optional—it’s a requirement. But precision isn’t just about clean data; it’s about interpreting what that data means. Subtle misinterpretation can quietly derail projects, slow timelines, and waste scarce resources. That’s why this week at Dr. GPCR , we’re focusing on the hidden risks that undermine progress and how the right frameworks can keep your pipeline moving forward. This is a preview of what Premium Members access every week: industry insights, event updates, jobs, and classified publications—curated for scientists who need fast, actionable intelligence. 🔍 This Week in Premium: Sneak Peek Dr. GPCR Premium Members this week gain curated, early access to: Industry insights : GPCRs and mRNA in drug discovery; new strategies for inflammatory disease treatment; growth strategies from Tectonic Therapeutics Upcoming events : Lab-in-the-Loop AI-powered hit discovery (July 29); 5th Transatlantic GPCR Symposium (Sept 3–4); neuroGPCR Symposium (Sept 17) Career opportunities : Lead/Senior Researcher at St. Jude; Postdoctoral Fellow at University of Copenhagen; PhD in proteomics and GPCR signaling in cancer at CRCM Must-read publications : AlphaFold3 benchmarking for GPCRs; new structural insights into peptide ligand activation All curated for speed, relevance, and immediate application—only for Premium Members. Terry’s Corner: Rethinking Affinity, A Critical Edge for Drug Hunters One of the most persistent misconceptions in pharmacology workflows? The interpretation of high and low affinity binding sites on GPCRs. At first glance, when a ligand binds at two different affinities in the same system, it seems logical to assume two distinct sites. But Terry Kenakin’s new Emerging Drug Hunter lecture reveals why this assumption can mislead even experienced teams . What’s Really Going On? Under certain experimental conditions, what appears to be a second high-affinity site may simply reflect kinetic factors—such as ligand-receptor-G protein complex formation—creating the illusion of multiple sites that aren’t physiologically relevant. This misunderstanding leads to: Inefficient structure-activity relationship (SAR) cycles Wasted optimization efforts Focus on leads that fail later in development In this exclusive session, Kenakin gives you the frameworks needed to interpret data correctly, eliminate wasted effort, and accelerate confident decisions. 🔒 Available only in Terry’s Corner - Premium Members get an exclusive discount Secure Your Access To Terry's Corner ➤ Why the Myth of Multiple Affinity Sites Slows You Down Traditional models that shaped affinity analysis were designed for simpler systems. If you’re not accounting for their limitations today, your team risks costly misinterpretations that delay optimization cycles and waste resources. Kenakin shows exactly how to separate what matters from what misleads—practical, real-world expertise designed to help teams move faster, smarter, and with greater confidence. Every day spent misunderstanding apparent affinity differences delays key milestones. 🗣️ “Thank you for bringing this (Principles of Pharmacology I) course with Dr. Kenakin. I wish Dr. GPCR the best for the sake of promoting more educational opportunities that are sorely needed in the field” — Dr. GPCR University Learner Celtarys Research Recap: Medicinal Chemistry Highlights You May Have Missed The pace of innovation in medicinal chemistry is accelerating—and if you missed this year’s ACSMEDI-EFMC Medicinal Chemistry Frontiers 2025 , you’re already behind. At this international meeting, leaders shared next-gen strategies shaping modern drug discovery: Prof. Ingo Hartung : State-of-the-art design of small molecule drugs, including PROTACs Dr. Wendy Young : Career insights and lessons from a leader in drug development and a champion for women in science Dr. Katerina Leftheris : New technologies overcoming peptide limitations with insights from both pharma and startup environments Read Maria Majellaro's Full Recap ➤ Lab Leadership Without Ego: A Model for R&D Success Scientific rigor doesn’t thrive in cultures defined by micromanagement or burnout. At Alkermes, Sokhom Pin built an in vitro pharmacology group from scratch—not just a lab, but a culture that encouraged curiosity, empowered people, and supported balance while delivering results. His leadership principles: Hire for attitude and team fit—not just credentials Design workflows that enable curiosity-driven research Support work-life balance without compromising scientific excellence His approach didn’t just create a productive lab—it accelerated outcomes and laid the cultural foundation for the next generation of biotech innovation. Get The Full Story ➤ Why Dr. GPCR Premium Membership Gives You an Edge Dr. GPCR Premium is designed for scientists who need the right intelligence, fast—without noise, distractions, or delays. Every week, members get: A full edition of GPCR Weekly News : jobs, events, papers, industry updates Exclusive discounts on Terry’s Corner  digital pharmacology courses Priority access to insights from major conferences, emerging research, and expert commentary Whether you’re a pharmacologist, biotech scientist, or team leader, Dr. GPCR Premium gives you an edge in a fast-moving field. FAQ: What’s Included, Who It’s For, Why Now What’s included? The complete Weekly News digest, jobs, upcoming events, classified industry intelligence, Courses, & Conference Presentations. Who is it for? Scientists, drug discovery teams, and pharmacologists who need curated, career-relevant updates. Why now? The field is evolving rapidly. Those acting on the right insights now will define the next wave of discovery. Don’t Fall Behind—Access the Edge You Need 👉 Access all the news and upcoming events ➤ Already a Premium Member? Access this week’s full Premium Edition here ➤ Hashtags: #GPCR #DrGPCR #BindingAffinity #Pharmacology #DrugDiscovery #LeadOptimization #TerryKenakin #EmergingDrugHunter #EfficientDiscovery #PipelineAcceleration

October 2022 "The activity of dopamine neurons is dependent on both intrinsic properties and afferent interaction between G βγ subunits and GIRK channels determines both the amplitude and kinetics of GPCR-dependent

October 2022 High hedgehog signaling is transduced by a multikinase-dependent switch controlling the

September 2022 Exploiting Dependence of Castration-Resistant Prostate Cancer on the Arginine Vasopressin

October 2022 Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent to use endocytosis to promote cellular cAMP signaling that drives downstream transcription of cAMP-dependent We show that epitope-tagged GCGRs undergo clathrin- and dynamin-dependent endocytosis in HEK293 and Huh We verify endocytosis-dependent induction of PCK1 expression by endogenous GCGRs in primary hepatocytes

October 2022 Cholesterol-Dependent Dynamics of the Serotonin1A Receptor Utilizing Single Particle Tracking

ago, GPCR activity was shown to be regulated by membrane potential in vitro, but whether the voltage dependence Here we show that muscarinic GPCR mediated neuronal potentiation in vivo is voltage dependent. Together, this study identifies a physiological role for the voltage dependency of GPCRs by demonstrating crucial involvement of GPCR voltage dependence in neuronal plasticity and behavior. Thus, this study suggests that GPCR voltage dependency plays a role in many diverse neuronal functions

October 2022 β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling

September 2022 "G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes that regulate a wide range of physiological processes and are popular drug targets. Serotonin1A receptors are important members of the GPCR family and are implicated in neuropsychiatric disorders. Cholesterol is a key constituent of higher eukaryotic membranes and is believed to contribute to the segregated distribution of membrane constituents into domains. To explore the role of cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking (SPT) to monitor diffusion of serotonin1A receptors under acute and chronic cholesterol-depleted conditions. Our results show that the short-term diffusion coefficient of the receptor decreases upon cholesterol depletion, irrespective of the method of cholesterol depletion. Analysis of SPT trajectories revealed that relative populations of receptors undergoing various modes of diffusion change upon cholesterol depletion. Notably, in cholesterol-depleted cells, we observed an increase in the confined population of the receptor accompanied by a reduction in diffusion coefficient for chronic cholesterol depletion. These results are supported by our recent work and present observations that show polymerization of G-actin in response to chronic cholesterol depletion. Taken together, our results bring out the interdependence of cholesterol and actin cytoskeleton in regulating diffusion of GPCRs in membranes." Read more at the source #DrGPCR #GPCR #IndustryNews

pharmaceutical company pioneering allosteric modulation-based drug discovery and development, today reported its half-year

By combining fiber photometry with FRET-based biosensors, we were able to track GPCR-dependent signaling

September 2022 Roles of Focal Adhesion Kinase PTK2 and Integrin αIIbβ3 Signaling in Collagen- and GPVI-Dependent Formation under Shear "Glycoprotein (GP)VI and integrin αIIbβ3 are key signaling receptors in collagen-dependent Here, we focused on disclosing the integrin-dependent roles of focal adhesion kinase (protein tyrosine kinase 2, PTK2), the shear-dependent collagen receptor GPR56 (ADGRG1 gene), and calcium and integrin-binding - and GPVI-dependent thrombus formation, which is modulated by GPR56 and exclusively at high shear.

Latrophilin-1 drives neuron morphogenesis and shapes chemo- and mechanosensation-dependent behavior in

A role for BET proteins in regulating basal, dopamine-induced and cAMP/PKA-dependent transcription in One candidate effector of PKA-dependent transcriptional regulation is the BET protein Brd4. findings identify the BET protein family, and Brd4 in particular, as novel regulators of basal and D1R-dependent

behave completely differently , and how the secret lies in receptor conformational dynamics , probe dependence ligand alters receptor conformation—and why this can’t be ignored  ✅ Practical examples of how probe dependence What If the Same Site Behaves Differently Depending on the Ligand? (It Often Does) A central concept explored here is probe dependence : the idea that the effect of an allosteric modulator depends entirely on the probe it interacts with.

September 2022 Endothelin-1 Stimulates PAI-1 Protein Expression via Dual Transactivation Pathway Dependent

in dense receptor environments  amplifies target occupancy, even post-clearance ✅ Insight into why half-life Why Half-Life Can Lie to You Most teams use systemic half-life as a proxy for action.

The problem is their long half-life, which results in lower detection efficiency. Another common radioactive atom, 125I, with a higher specific activity, but a shorter half-life (60 days The choice between these two depends on the results needed – but in case they are similar, fluorescent

Core message: The receptor is only half the story. The molecule is the other half.

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

disease therapy Primary cilia in skeletal development and disease Industry News Addex Reports 2023 Half Trial with Cancer Immunotherapy Drug HTL0039732 Exscientia Business Update for Second Quarter and First Half

Topline results from 40 subjects are expected in the second half of the calendar year."

started from inactive conformation using molecular dynamic simulations Kinetic insights into agonist-dependent From Indivior In Extended Substance Use Disorder Research Collaboration Addex Therapeutics To Release Half-Year hand Sosei Heptares Operational Highlights and Consolidated Results for the Second Quarter and First Half

Particular emphasis is given to findings from the past decade and a half that highlight the emerging

Historically, drug discovery efforts targeting GPCRs focused on G-protein-dependent signaling pathways players in activating extracellular signal-regulated kinases (ERK) pathways alongside the G-protein dependent small GTPases like RAS leads to the activation of the MAP kinase kinase kinases (MAPKKKs), such as RAF RAF then phosphorylates and activates the MAP kinase kinases (MAPKKs), MEK1 and MEK2, which in turn phosphorylate ERK-dependent apoptosis as a potential therapeutic strategy for cancer. Cells, 10(10), 2509.

Let’s build the systems now, before the next delay burns another half a million. 🚀 Book your free 30

MI was introduced to rats by permanent left anterior descending coronary artery (LAD) ligation. Under normal conditions, β-catenin is degraded in the cytoplasm by the active GSK3β-dependent degradation

Persistent binding isn’t just about longer half-lives—it’s about smarter pharmacology.

they engineered a two-dimensional pH response: probes that get brighter and glow longer as receptors descend

the field will have to face in the next 10 years is deciphering the physiological relevance of splice-dependent a lot of firsts in this perspective: the first time in a LATAM country, the first organized by Afro-descendants PMID 38421639 Systematic assessment of the tethered agonist-dependent activities of all 33 aGPCRs in