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Watch Episode 170 What We’re Missing in Pain Research In GPCR drug discovery, receptors typically steal the spotlight. But as Dr. Alex Serafini  pointed out in his interview, Regulators of G protein Signaling (RGS proteins)  might hold some of the most untapped therapeutic opportunities, particularly in pain neuroscience. Serafini described his connection to GPCRs as tangential but inevitable: "I feel like I never was particularly explicitly interested in GPCR signaling... but the thing about GPCRs... is you always kind of end up landing at a GPCR as a major target." His work in the lab of Dr. Venetia Zachariou  introduced him to the power of RGS proteins — particularly RGS4  — in modulating pain circuits in ways that traditional targets fail to capture. RGS4 and the Unexpected Recovery Phenomenon One of the most compelling findings in Serafini’s experience was the spontaneous recovery observed in RGS4 knockout mice . “There was this very interesting phenotype the lab found where, as a mouse was starting to enter what we consider the chronic pain range, the mice that were constitutively RGS4 knocked out started recovering spontaneously. And this is a recovery that is very rare to see at the preclinical level. " Such recovery is rare in preclinical pain models and hints that RGS proteins could modulate pain chronification itself . These findings suggest a path forward that isn’t about blocking a single receptor but about rewiring the entire system upstream of pain perception. Serafini noted that RGS4 was especially intriguing because it was expressed robustly both in the peripheral nervous system and in central circuits like the prefrontal cortex and thalamus  — areas deeply involved in both pain perception and affective comorbidities. GPCRs in the Background, But Always Present Even though his primary focus wasn’t GPCRs themselves, Serafini repeatedly encountered them as unavoidable players in pain-related pathways. Whether working on opioid withdrawal, addiction vulnerability, or chronic pain, GPCR-related signaling repeatedly emerged as the core mediator  — demonstrating the reach of these signaling pathways beyond classical receptor pharmacology. This realization isn’t isolated. Serafini highlighted that in modern pain drug development, the field has remained too focused on ion channels like NAV1.8 , despite these targets falling short clinically: “The downstream cascade is probably a little bit weaker than if you were hitting a GPCR... and honestly, like with the trials, they were not really that sufficiently better than opioids, right? And in itself, that's kind of a suggestion.” Takeaway Forget what you think you know about GPCR drug targets. The real power may lie in how they’re regulated. Dr. Serafini’s work on RGS proteins suggests a quieter, but no less powerful, frontier in the fight against chronic pain. ___________ Keyword Cloud: RGS4 , GPCR data platform , GPCR training program , pain research , opioid signaling .

Welcome GPCR Fans,   Every discovery-phase decision you make shapes your entire pipeline trajectory—and understanding when equilibrium affinity falls short is no longer optional. That’s exactly what Terry’s Corner  delivers this week: real-world kinetic frameworks to help you move faster and make smarter choices. Breakthroughs this week: Structure-based discovery of positive allosteric modulators of the A1 adenosine receptor; GPR171 is necessary for normal physiological functions and mood-related behaviors in males, but not females; Discovery on Target GPCR Drug Discovery. 🔍 This Week in Premium: Sneak Peek A curated preview of this week’s Premium classified content — designed to keep you ahead without noise or delays: Industry insights:  Structure-Based Drug Design Summit; AI-Powered GPCR Research; Lab-in-the-Loop Hit Discovery advances. Upcoming events:  5th MMCS New Trends in Drug Discovery; GPCR-UK Network Meeting; neuroGPCR Symposium. Career opportunities:  Principal Scientist - In Vitro Pharmacology; Senior Scientist, Molecular Pharmacology; PhD position in proteomics and GPCR signaling. Must-read publications:  GPCRchimeraDB: Database of engineered GPCR designs. All curated for speed, relevance, and immediate application—only for Premium Members. Terry’s Corner: Why Binding Kinetics Matter More Than Affinity In drug discovery today, time wasted is opportunity lost. Yet too many programs rely solely on affinity metrics—Kd—as proxies for in vivo behavior, missing a critical layer of insight: kinetics. Terry Kenakin’s latest lecture in Terry’s Corner  delivers exactly what your discovery teams need now: a pragmatic framework to interpret kinetic binding experiments and recognize when a drug’s rate of onset and offset matter more than affinity itself. Prevent wasted cycles:  Avoid costly delays caused by false positives from static affinity readouts. Gain operational clarity:  Learn how kinetics signal which compounds will truly perform in vivo—under competitive, real-world conditions. Stay ahead of competitors:  Know when your data reflects equilibrium and when to probe deeper, ensuring your team doesn’t misinterpret key signals. Premium Members get 50%+ discount when they join Terry’s Corner. 🔒 Available only in Terry’s Corner - Premium Members get an exclusive discount Sharpen your discovery decision ➤ 🗣️ “Dr. Kenakin is a masterful teacher and communicator—and a leading expert in our field.” — Dr. GPCR University Course Attendee Dr. GPCR Podcast : From Personal Pain to Scientific Purpose: Alex Serafini’s Journey We sit down with Dr. Alex Serafini, whose unconventional path—from patient to scientist—exemplifies why personal mission matters in translational research. Serafini’s early struggles with chronic pain sparked a career focused on innovating where pain management has long stagnated. His work challenges outdated targets, explores overlooked roles of GPCRs and RGS proteins in pain, and seeks to redefine translational models for patient realities. Redefine your playbook:  Why Serafini believes that pain research needs to start from clinical phenotype and work backward. Explore blind spots:  The underestimated role of GPCRs and RGS proteins in chronic pain mechanisms. Rethink translational success:  How post-COVID insights and unconventional decision-making shaped Serafini’s high-impact projects. Watch the conversation ➤ Event: Where the Next Decade of GPCR Therapies Will Be Defined The 20th annual Discovery on Target GPCR-Based Drug Discovery  meeting is where the next wave of therapies—from allosteric modulators to computational targeting—will take shape. If you’re not there, you’re missing an opportunity to benchmark your strategy against the best in the field. Terry Kenakin’s featured talk on “The Kinetics of Allostery” offers a rare live glimpse into advanced kinetic thinking—but for full, actionable frameworks, only Terry’s Corner  members get exclusive on-demand access. Benchmark your roadmap:  See where competitors are heading before they act. Identify emerging targets:  Allosteric modulators, biased ligands, and kinetic frameworks will dominate the next wave. Get exclusive discounts:  Secure your seat now with code DRGPCR25 for $200 off. Secure your spot ➤ Why Dr. GPCR Premium Membership Gives You an Edge Premium delivers curated, noise-free intelligence every week: deep-dive expert lectures, classified industry news, priority event alerts, job opportunities, and insider commentary—all designed to help you move faster and smarter in an increasingly complex GPCR landscape. Stay focused, informed, and ahead of your competitors while saving critical time each week. 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. 🔹 Premium Membership FAQ 🔹 What’s included? The complete Weekly News digest, curated jobs, upcoming events, classified GPCR publications, exclusive on-demand expert frameworks, and member-only discounts. 🔹 Who is it for? GPCR scientists, translational pharmacologists, biotech drug discovery teams, and decision-makers who need fast, curated, career-relevant intelligence to stay ahead. 🔹 Why now? The pace of GPCR innovation is accelerating. Those acting on the right signals today will shape tomorrow’s breakthroughs—and avoid delays others won’t see coming. Don’t Fall Behind—Access the Edge You Need 👉 Ready to sharpen your discovery decisions? Join today and get instant access to exclusive insights, expert frameworks, and classified intelligence that give you a professional edge: Premium Signup Already a Premium Member? Access this week’s full Premium Edition here ➤    Access all the news and upcoming events Hashtags: #GPCR #DrGPCR #BindingAffinity #Pharmacology #DrugDiscovery #LeadOptimization #TerryKenakin #EmergingDrugHunter #EfficientDiscovery #PipelineAcceleration

Watch Episode 170 Why We’re Here What if your own body pushed you into science? For Dr. Alex Serafini, that’s exactly what happened. After years of living with unresolved pain following surgery for a pilonidal cyst, Alex was left without options — and without relief. Denied stronger medication in the midst of the opioid crisis, he turned to the one place that still offered answers: the lab. This is a story about how chronic pain doesn't just shape lives — it reshapes careers. From Patient to Researcher Alex wasn’t always planning to be a scientist. Born in California and raised in Silicon Valley, his early interests were in finance and business. But everything changed when his recurring pain — and the rigid protocols around opioid prescription — forced him to search deeper. “I wasn’t able to get stronger pain meds,” he said. “So I had to understand the biology myself.” His new obsession led him to Johns Hopkins, where he worked in the lab of Dr. Mike Caterina on pain mechanisms in the peripheral nervous system. There, he learned how to frame pain not just as a symptom, but as a signal — and a scientific challenge. The Value of Lived Experience in Science What makes Serafini’s trajectory so compelling isn’t just his technical training — it’s the urgency he brings to the field. His interest in model development, in capturing the lived human experience through preclinical systems, was born out of necessity. Building a Career from the Inside Out Now back in med school, Serafini aims to follow the physician-scientist path: part-time clinical work, mostly lab-based research. He’s focused on RGS proteins , pain comorbidities  like addiction and depression, and pushing for more accurate model systems. "When you talk to patients that have an unmet need, you learn things that no one is thinking about in terms of how to solve those problems." Takeaway Science isn’t always about curiosity. Sometimes, it’s about necessity. Dr. Alex Serafini’s journey proves how personal pain can lead to professional purpose — and why the next generation of pain researchers needs to start from lived experience, not just literature. _________________ Keyword Cloud: GPCR research community , chronic pain , GPCR drug discovery , GPCR scientist network , pain neuroscience

Think a drug just "locks into" a receptor and does its job? Think again. Join Terry Kenakin as he pulls back the curtain on the deceptively simple process of orthosteric binding—the first step in drug action. This isn’t just about molecules finding a pocket. It’s about a dynamic dance of chemical forces, equilibrium shifts, and molecular decisions that determine whether a compound works… or doesn’t. The Importance of Binding in Drug Action In pharmacology, binding must happen before any drug effect can take place. Understanding this process is crucial for anyone interested in drug development and action. When a drug binds to its target, it initiates a series of events that can lead to a physiological response. This foundational knowledge guides researchers in the development of new therapeutics. Key Concepts in Binding Terry unpacks several key concepts related to orthosteric binding: Langmuir Adsorption Isotherm : This concept teaches us about affinity. It explains how the concentration of a drug influences its binding to the receptor. A high affinity means the drug will bind more easily and effectively. Binding Curves : These curves reveal presence, not potency. They show how much of a drug is binding to its target but do not necessarily indicate how strong its effect will be. Understanding EC50 : The term EC50 refers to the concentration of a drug required to achieve 50% of its maximum effect. However, this doesn’t always mean what you think it means. Often, a low EC50 indicates high potency, but this isn't always the case due to various biological factors. 📚 Whether you're new to pharmacology or brushing up on basics, this lesson will change how you think about the very first interaction between drug and target. Unlocking the Secrets of Orthosteric Binding Understanding why some drugs bind better than others is crucial for drug efficacy. It can inform decisions in drug design, improving therapeutic outcomes and reducing unwanted side effects. 🔥 Want to understand why some drugs bind better—and why that matters? The Dynamic Nature of Binding Binding is not a static event. Instead, it involves a dynamic interaction between the drug and the receptor. The receptor may change shape upon binding, affecting how the drug interacts and how effective it will be. Additionally, competitive inhibitors can interfere with this binding process, leading to reduced efficacy. Implications for Drug Development As drug developers, understanding these nuances can significantly impact the success of new medications. By considering factors like the Langmuir adsorption isotherm and binding curves, researchers can better predict how a drug will perform in the body. This knowledge can guide modifications to improve binding affinity and bioavailability. Conclusion In conclusion, the process of orthosteric binding is complex and multifaceted. It goes beyond simple interactions. The dynamic interplay of chemical forces shapes drug effectiveness. Unlock "Orthosteric Binding" now and dive deeper into this fascinating topic. You'll gain valuable insights into the critical role binding plays in pharmacology. This understanding can enhance your appreciation for drug development and therapeutic action. By embracing these concepts, we can pave the way for more effective treatments in the future. Understanding the intricate details of drug-receptor interactions transforms how we approach pharmacology.

Why I Started GPCR Consulting You've got great data. You've got brilliant scientists. But your GPCR program still isn't moving at the pace it should. I've seen this pattern unfold across biotech, academia, and nonprofits. The assays are running, data is flowing in from your CROs or your internal labs , yet progress stalls. Decisions are slow, crucial data is siloed, and despite everyone working hard, programs drift. For over two decades, my work has centered on GPCR pharmacology . In every role and sector, I found myself drawn to the same critical challenges: missed opportunities, misaligned systems, and promising programs stalling despite strong science. I was always the one identifying what could be improved: The essential structure that was missing. The clarity that was desperately lacking. The unnecessary friction that slowed everything down. Traditional roles rarely gave me the freedom to implement these changes at the scale needed. So, I created a new path—one that allows me to embed, optimize, and accelerate GPCR programs from the inside out. The GPCR Data Dilemma: The Lego Bucket Problem I've seen promising GPCR programs generate massive volumes of high-quality data. But without structure, it's just a messy pile of colored blocks. I call this the Lego Bucket Problem . You have the data, but not the definitive direction. This disconnect frequently leads to: Underperforming assays. Internal data and CRO outputs  misaligned with strategic goals. Delays in critical go/no-go decisions. Frustrated teams and slipping timelines. It's not just a scientific issue—it's an operational one. You can't move fast without clarity, and you can't make confident decisions without robust structure. My Approach: Biology, Execution, Systems My consulting approach uniquely blends deep pharmacology expertise with the operational discipline required to make that expertise actionable. Here's how I bring a fresh perspective: Biology-First, Data-Driven Strategy:  I help you focus on the science that truly matters. We cut through the noise, elevate what's working, and strategically solve what's not, ensuring your GPCR program stays on target. Embedded Execution:  I work alongside your team—not above it. I'll help write CRO scopes, meticulously review assay data, flag risks early, and keep your programs relentlessly on track. Systems That Drive Progress:  From assay tracking to data workflows, I design simple, scalable tools that surface insights early and dramatically reduce delays, transforming your data into actionable intelligence. A Broader Lens: Dr. GPCR As the co-founder of Dr. GPCR, we've built a global hub connecting over 1,300 GPCR scientists dedicated to this field. These ongoing conversations keep me on the front lines, sharpening my understanding of the common bottlenecks and evolving needs across the entire GPCR community. My Consulting Philosophy This practice is built on three core values: Scientific Integrity:  Every recommendation is grounded in real-world evidence and extensive experience. Operational Discipline:  Robust systems and clear structure aren't "nice to have"—they are absolutely essential for efficient progress. Collaborative Partnership:  I embed, contribute, and build solutions hand-in-hand with your team. Ready to Move Your GPCR Program Forward? If you're navigating a stuck GPCR program, planning your next crucial milestone, or struggling to gain clarity from complex data, I'd love to help. 📌 Learn more about my services: Yamina.org 📅 Book a 30-minute strategy call: https://calendly.com/drgpcr/yamina-corner

Is Your GPCR Program Slowing Down—Even With Good Data? You’re not alone. Most teams don’t stall because the science is weak. They stall because the data becomes a mess. I call it the Lego Bucket Problem : You’ve got CRO output, internal assay data, maybe even some promising signals. But there’s no blueprint. No structure. No clear path to your next milestone. Meetings drag. Decisions stall. And momentum quietly dies. The Hidden Cost of Good Science Without Systems I’ve seen this pattern again and again—across academia, biotech, and through close work with dozens of teams inside the Dr. GPCR Ecosystem. Strong science. Promising data. But no systems to turn it into momentum. Data arrives too fast and too fragmented CROs deliver output without clear integration Teams chase the wrong assays, too late to pivot Milestones slip—and nobody realizes until it’s too late Failing fast? Not possible when nothing’s built to surface the right  insights early. That’s Why I Built Yamina’s Consulting Corner This is not “advising.” This is embedded consulting for biotech and VC teams who need to move fast —without compromising scientific integrity. Unlike traditional advisors, I'm not just observing; I'm part of your team . This allows me to experience your challenges firsthand, identify roadblocks faster , and i mplement solutions from within , ensuring genuine buy-in and lasting momentum. Here’s what I bring: Biology-First Strategy I’ve designed GPCR assays, led collaborations across research environments, and translated complex data into action. I know how to ask the right scientific questions—and when to shift from analysis to execution. Systems That Drive Execution No more disconnected slides and 6-week meeting cycles. I install simple tools that surface insights, align your team, and keep momentum moving. True Embedded Partnership I review CRO scopes, flag risks early, and sit in on your strategic calls. I’m not watching from the sidelines—I’m driving with you. Real-Time Global Insight As founder of Dr. GPCR, I’m connected to 1,300+ scientists and decision-makers worldwide. That network gives me a constant pulse on what’s working—and what’s next. Who I Work With ✅ Biotech Teams  – Especially those lacking in-house GPCR leads or overwhelmed by CRO data chaos. ✅ Venture Capital Firms  – Looking to accelerate, troubleshoot, or validate GPCR assets in their portfolio. ✅ Contract Research Organizations (CROs)  – Wanting to better align with biotech clients and deliver real  insight, not just data. My Consulting Philosophy Every successful GPCR program is a blend of scientific excellence  and operational precision . One without the other will quietly kill your momentum. My work is rooted in: ✔️ Scientific Integrity ✔️ Operational Discipline ✔️ Collaborative Partnership Let’s Get Your GPCR Program Moving Again Whether you’re building from scratch or recovering from a stall, I’ll help you move faster—with fewer blind spots, tighter execution, and a clear line of sight to your next key decision. 🚀 Book your free 30-minute strategy call Let’s unlock the momentum your GPCR program needs. 👉 https://calendly.com/drgpcr/yamina-corner Or explore how we can work together: 👉 Yamina.org 🔑 Key Takeaways ✅ Even strong science stalls without operational structure ✅ Scattered data = missed insights = wasted time ✅ You can’t fail fas t if you can’t see the problems early ✅ Most teams don’t need more data— they need clarity ✅ Yamina’s Corner helps teams move from data chaos to decisive action ✅ This is hands-on support —not passive advising p.s: Still unsure if this is the right fit? Let’s talk through your program—no pitch, just clarity.

Watch here Trends come and go. Scientific fads rise and fall. But Sokhom Pin stayed loyal to GPCRs , even when big pharma turned its gaze to other targets like kinases and checkpoint inhibitors. Riding the GPCR Rollercoaster Early in his career at DuPont and BMS, GPCRs were red hot. High-throughput screening for receptor ligands was booming, and Sokhom was at the center of it. But then came the industry shift. “Companies started shutting down neuroscience and GPCR programs. But I stayed,” Sokhom said. While others pivoted, Sokhom went deeper: refining assays, exploring signaling bias, and building a robust knowledge base in one of the most pharmacologically diverse receptor families. The Payoff of Staying Focused Today, GPCRs are making a comeback in popularity. Advances in biased signaling, allosterism, and endosomal signaling have opened new therapeutic frontiers. And Sokhom? He’s one of the few who never left. “Because the field became unpopular for a while, they stopped training new experts. Now, there’s less competition and more opportunity.” A Career Built on Consistency From CGRP receptor antagonists at BMS to opioid receptor research at Alkermes and early-stage work at Cerevel and Superluminal, Sokhom’s consistency has paid off in ways short-term thinkers often miss. _______________ Keyword Cloud: GPCR drug discovery , G protein-coupled receptors , GPCR webinar series , GPCR scientist network , GPCR research community

Watch Episode 169 Leadership in science isn't just about results, it's about people. At Alkermes , Sokhom Pin wasn’t just leading GPCR programs; he was building culture from the ground up. And that culture worked. The Challenge: Build a Team. Build a Lab. Build the R in R&D. When Sokhom joined Alkermes, the company had a strong development arm, but a relatively underdeveloped research function. He was tasked with building an in vitro pharmacology group from scratch , including infrastructure, hiring, assay development, and team dynamics. “I couldn’t sleep. I was up every night thinking about how to hire, how to lead, how to avoid the mistakes my bad bosses made,” Sokhom said. What Made It Work He focused on empowerment , not micromanagement He hired based on attitude and team fit , not just credentials He designed lab workflows that encouraged curiosity without burnout He supported work-life balance while maintaining scientific excellence The result? His team was known internally as the “happiest group at Alkermes.” Why Culture Matters in Drug Discovery You can’t innovate under pressure. In a field like GPCR research (where data complexity and failure rates are high), scientific rigor thrives when trust and collaboration lead the way. Sokhom knew this instinctively and built a system to support it. From Lab Bench to Boardroom His work at Alkermes didn’t just improve drug screening outcomes, it redefined what great leadership in biotech looks like . It was the foundation for his next opportunity: helping launch Cerevel from the ground up. ________________ Keyword Cloud: Dr. GPCR ecosystem , GPCR research community , GPCR podcast , GPCR data platform , GPCR training program

Watch Episode 169 What if you could earn a PhD while supporting a family and working full time in drug discovery? That’s exactly what Sokhom Pin did. In a field where traditional academic paths often dominate the narrative, his story offers a powerful alternative. Breaking the Mold Most scientists follow the usual script—graduate school, lab rotations, dissertation defense. But Sokhom’s journey started differently. As a lab technician at Johns Hopkins, he was fascinated by science but also grounded in real-life responsibilities. With a growing family and a full-time position, traditional PhD training just wasn’t an option. Instead of choosing between academia and career, he engineered a third path : a partnership between BMS and UConn that allowed him to do industry-based research while pursuing his doctorate. “I couldn’t afford to quit my job. So I designed my own PhD program,” Sokhom shared. How It Worked BMS funded the research, salary, and even tuition UConn accepted the research done in the BMS lab as part of the dissertation Sokhom met weekly with advisors and monthly for presentations All research was publication-quality, high-impact, and strategically focused This approach allowed him to avoid the experimental churn common in academia. He only pursued experiments that were scientifically sound and directly publishable, a skill honed from years of hands-on work in high-throughput screening. A Model for Future Scientists? Sokhom’s experience speaks to a larger truth: there’s no single way to become a scientist . His hybrid path is a model of possibility for professionals in the biotech industry who still dream of earning advanced degrees without leaving the bench, or their paycheck, behind. Takeaway If you’re navigating work, life, and scientific ambition, Sokhom Pin proves it’s possible to have it all, if you design it yourself. _________________ Keyword Cloud: GPCR training program , GPCR scientist network , GPCR drug discovery , G protein-coupled receptors , GPCR online course

Welcome Back, Discovery Drivers   Terry’s Corner is live, on-demand pharmacology built for drug discovery. Yamina’s Corner opens for strategic consulting, and our partner Celtarys unveils a robust TR-FRET assay for CBRs. Plus: must-read chemokine and PTH1R papers, and new momentum across biotech—from Superluminal to Neurocrine to novel GLP-1 contenders. Dr.GPCR Updates Terry’s Corner is Live - Pharmacology at your fingertips Terry’s Corner is now open! Explore 10 on-demand lessons by Dr. Terry Kenakin with short videos, clear summaries, and curated references. New and unique lessons are released weekly on Tuesday. Elevate your drug discovery program with 45+ lessons yearly. Premium Members:  Get your exclusive discount code in this week’s full edition of the this newsletter accessible at the bottom of this email.   Join Terry’s Corner Today Yamina’s Corner Is Live – Are you drowning in disorganized data? Yamina’s Corner delivers GPCR consulting that cuts through the noise, designing assay cascades, setting go/no-go points, and de-risking programs from hit validation through development candidate selection and beyond. With a biology-first strategy, embedded execution, and scalable systems, it turns scattered data into decisions, accelerating your path to a successful preclinical program. Because even the best data means nothing without structure. That’s the Lego Bucket Problem.    Visit Yamina’s Corner Now CELT-335 - Celtarys Validates New Assay for CB1/CB2 Screening Dr. GPCR partner Celtarys Research has validated a TR-FRET assay for cannabinoid receptor ligands using their probe CELT-335. With nanomolar affinity, high specificity, and a strong signal-to-noise profile, this non-radioactive, cell-compatible platform is ready for your next SAR-driven screening campaign.   Read The Full Article GPCR Publication Highlights   Chemokine–GPCR Selectivity Unveiled Sequence- and structure-based analysis reveals how conserved and variable regions across chemokines and their receptors drive selectivity and promiscuity, paving the way for rational ligand design.   Decoding PTH1R Gq Signaling Cryo-EM structures of Gq-bound PTH1R uncover glycan and loop-based mechanisms shaping G-protein preference, offering a path toward signaling-biased osteoporosis therapies.   Distinct Ligand Activation in NMBR Simulations show how two ligands differently activate class A GPCR NMBR, with allosteric communication hubs modulating signaling, advancing antipruritic drug strategies. Want the full breakdown and your discount code for Terry's Corner? Better pharmacology leads to better decisions—unlock it now with Terry’s Corner. Stay curious,   The Dr. GPCR Team Join Our Newsletter! To start receiving our newsletter in your inbox every Thursday, follow these simple steps: Select the Log In / Sign Up option located at the top right corner of the header. Select ' New to this site? Sign Up' Complete the registration form. Stay updated with the latest news and insights by signing up today!

Picture this: two compounds bind to the same receptor. One sparks a firestorm of cellular activity. The other? Silence. Why? The answer lies in a misunderstood property called efficacy—the power of a drug to trigger a response after  binding. In Terry Kenakin’s latest lesson, you’ll uncover why efficacy is the unsung hero of drug discovery and how its effects depend entirely on the biological system it’s tested in. This isn’t just a theory class. Terry walks you through real-world experiments, decades of receptor pharmacology wisdom, and the cutting-edge operational model used to quantify efficacy. You'll learn why some agonists succeed in sensitive tissues but fail elsewhere—and how this knowledge can dramatically shift your screening strategy. If you’re stuck trying to figure out why your lead compound looks promising in vitro but flops in vivo, you need this lesson. Ready to think beyond binding? 🔓 Find the lesson in Terry’s Pharmacology Vault: “Efficacy and System Sensitivity Unlock "Agonism & Efficacy" now

What do roasted ox liver and AI-powered virtual screening have in common? They both mark critical moments in humanity’s centuries-long quest to control physiology—and they bookend a story few new learners truly understand. In this exclusive foundational-level lecture, Dr. Terry Kenakin takes you on a captivating tour through the history of pharmacology : a journey that spans ancient Egypt, revolutionary scientific ideas, Nobel Prize-winning discoveries, and today's digital frontier. But this isn't just about what was —it's about why the past matters now. Ever heard of the Ebers Papyrus? It’s one of the earliest medical texts, prescribing liver to treat night blindness. (Spoiler: It worked—thanks to Vitamin A.) Fast-forward a few thousand years, and we’re talking beta receptors, receptor theory, and AI-generated ligands. All of it connected. All of it is essential. Dr. Kenakin also celebrates the giants on whose shoulders we stand—A.J. Clark, Paul Ehrlich, Sir James Black, and more—sharing the stories and setbacks that shaped today’s scientific frameworks. And yes, you'll even meet the man who turned failed experiments into a Nobel Prize-winning discovery about nitric oxide. Whether you're stepping into pharmacology for the first time or rekindling your interest, this lesson delivers 'aha' moments  grounded in decades of experience. It's equal parts inspiration, insight, and orientation. Curious yet? 👉 Join Terry’s Corner, your essential launchpad into the world of therapeutic science Unlock "The History of Pharmacology" now

What if one simple graph could reveal the true power of a drug? In the newest foundational lesson from Terry Kenakin’s Pharmacology Vault , we unlock the visual language of pharmacology: dose-response curves . From assessing drug potency to predicting effects, these curves aren't just for data—they’re your entry point to understanding drug behavior at a deeper level. In classic Terry style, the lecture walks you through: What dose-response curves are and why they’re indispensable How curve-fitting models can  deceive—and how to avoid being misled The statistical tricks that elevate a rough curve into a real insight You'll leave with practical tools and a new appreciation for the humble curve that powers drug discovery. Want to finally understand EC50 without squinting at formulas? Ready to grasp how a curve can mislead—or enlighten? 👉 Discover why dose-response curves are the backbone of all pharmacology. Unlock "Dose-Response Curves" now

What if the way we've been studying GPCRs—arguably the most important drug targets in pharmacology—has been wrong… or at least, incomplete? In the foundational lesson of Terry’s Corner , Dr. Terry Kenakin invites us to challenge outdated assumptions and step into a new era of drug discovery. With insights from molecular dynamics, biased signaling, and allosteric modulation, this session lays bare the science that’s reshaping how we develop medicines. Here’s the surprising truth: up to 80% of GPCR-targeted drugs fail—not because of poor chemistry, but because we’ve misunderstood how these shape-shifting proteins truly behave. Now, Terry is opening the vault. This isn’t theory. It’s 40 years of hard-won insight distilled into accessible, high-impact content designed for learners just starting out. This is your chance to get ahead of the curve. Join Terry’s Corner and stay updated on the latest in GPCR research—delivered in a format that’s as approachable as it is transformative. 👉 Ready to understand what your molecules are really doing? Unlock "Why Terry's Corner" now

Hello GPCR Innovators ,   We’re preparing to launch Terry’s Corner, a new knowledge hub shaped by Dr. Terry Kenakin’s decades of GPCR insight. It will bridge foundational receptor theory with today’s most pressing pharmacological questions, from biased signaling to allosteric design.   Meanwhile, incretin and amylin-based therapies are reshaping the obesity drug landscape. Novo Nordisk’s amycretin showed up to 24% weight loss, CagriSema delivered 22.7% in Phase 3, and semaglutide’s Canadian patent expiry is opening competitive pathways. Eli Lilly’s next moves with Orforglipron and its amylin analog are highly anticipated.   Plus, Celtarys explores ligand selection for better assays, and co-founder Dr. Maria Majellaro shares her story of innovation and listening-driven science.   This week’s publication highlights: CXCR4 takes on a nuclear role in red blood cell maturation CXCL13/CXCR5 emerges as a high-potential pain target ST171, a biased 5‑HT1A agonist, delivers selective pain relief in preclinical models Dr.GPCR Updates Terry’s Corner  – Build Better GPCR Screens with Dr. Kenakin   Four decades of receptor theory now fit in one expert-guided hub. Terry’s Corner gives you timeless and timely tools to improve selectivity, model efficacy, and design smarter GPCR pharmacology screens, anchored in real-world lessons and cutting-edge science.   Sign Up for The Kenakin Brief Fluorescent Ligands vs. Radioligands – Assay Smarter Celtarys explores how fluorescent ligands enable safer, high-throughput screening with rich kinetic data. Learn how these tools help retain assay integrity while eliminating radioactivity—perfect for next-gen GPCR workflows.    Upgrade Your Screening Strategy Leadership in Ligand Design  – The Celtarys Origin Story   In  this founder interview , Dr. Maria Majellaro reveals how Celtarys evolved from a vision into a company solving real-world assay problems. It’s a story of leadership, scientific rigor, and tools built for the needs of modern discovery teams.   Read Maria’s Story GPCR Publication Highlights   CXCR4 signaling promotes terminal erythropoiesis  through nuclear translocation and perinuclear calcium bursts.  Blocking this chemokine axis reduces pain  hypersensitivity by dampening neuroinflammation and glial activation.  This novel agonist activates Gi/o selectively , avoiding β-arrestin and showing strong pain relief in preclinical models. Want the full breakdown? Explore this week’s research, tools, and biotech insights in one place. Stay curious, stay connected, because the future of GPCR science is being written pathway by pathway.   Best,   The Dr. GPCR Team

Ever wondered why a drug behaves like a miracle in one tissue and a dud in another? Welcome to Terry’s Corner , where foundational pharmacology is demystified by someone who’s spent over 40 years navigating the complexity of drug discovery. In his newest lesson, “The Uniqueness of Pharmacology in Drug Discovery,” Terry Kenakin explains why pharmacology isn’t a clean-cut science—it’s a dynamic dialogue between molecule and system. You’ll uncover: Why pharmacology is the glue between chemistry and biology How to interpret drug behavior across tissues The truth behind those “confusing” lab results that seem contradictory This lesson isn’t just academic—it’s practical knowledge every early-stage scientist needs. Whether you're heading into your first assay or trying to make sense of inconsistent data, Terry gives you the tools and mindset to understand what's really  happening. Don’t just look at the data—learn how to read the story it’s telling. 👉 Start your journey with Terry’s foundational series Unlock "Unique Role of Pharmacology" now

What happens between identifying a target and delivering a life-saving treatment? How do molecules make the leap from laboratory concept to therapeutic reality? Step into the world of drug discovery with Dr. Terry Kenakin , a veteran pharmacologist with over 40 years of industry experience. In this foundational-level  lesson, Terry unpacks the real-life process behind discovering new drugs, breaking down the science into accessible, engaging insights for early learners and curious minds. You’ll explore: What makes a “discovery team” tick (and why teamwork is non-negotiable) The difference between Me Too  and First in Class  projects—and why both are essential Why target-based  discovery is powerful, but can miss the forest for the trees The critical importance of translation —turning lab data into meaningful therapeutic outcomes Terry’s unique ability to combine storytelling, real-world experience, and scientific clarity makes this more than just a lecture—it’s a launchpad. If you're just beginning your pharmacology journey… This is the lesson that will connect the dots. You’ll leave with the language, logic, and big-picture view that underpins all future learning in pharmacology and drug development. Don’t miss your chance to learn from one of the best: Unlock “Introduction to Drug Discovery" now

Watch Episode 168 In drug discovery, tools matter, but so do people. In Episode 168 of the Dr. GPCR Podcast, Dr. Maria Majellaro makes it clear that Celtarys isn’t just a ligand provider. It’s a scientific partner. And that mindset is precisely what makes their new partnership with Dr. GPCR so powerful. “We don’t just deliver compounds, we solve assay problems.” — Dr. Maria Majellaro Celtarys specializes in the custom development of fluorescent ligands  using a modular chemistry platform. Their method allows researchers to explore different linker positions, tailor activity (agonist or antagonist), and retain biological function, all while skipping the time-consuming synthetic routes common in the field. But what sets them apart isn’t just chemistry. It’s empathy. Maria emphasizes the importance of genuinely listening to researchers: understanding the biological question first, then building a tool to match it. Whether supporting CROs, academic labs, or pharma teams, Celtarys engages deeply with collaborators to deliver not just reagents but solutions. “We want to illuminate biology. That’s the mission. ” — Dr. Maria Majellaro Now, as official partners of the Dr. GPCR ecosystem , Celtarys is opening up that model to the broader research community. The goal? Democratize access to high-performance chemical probes and make assay development faster, cheaper, and more customizable. 👉 See how Celtarys can support your drug discovery workflow on the company page . _______________ Keyword Cloud:   GPCR data platform , fluorescent ligands , assay development , GPCR research community , Dr. GPCR ecosystem , GPCR webinar series

Hello GPCR Minds,   This week, you'll learn all about Terry’s Pharmacology Corner, your new learning space focused on GPCR pharmacology. Whether you’re early in your career or pushing the edge of MoA design, weekly lesson help you apply key concepts like binding, signaling, and kinetics in practical, decision-shaping ways. The Corner comes will live monthly AMA sessions with Dr. Kenakin. Get curated content at your own pace.   Subscribe to The Kenakin Brief below to stay in the know. Celtarys Research expands its assay tools with CELT-419 for D3 receptor studies, and Dr. Maria Majellaro shares her journey to founding Celtarys in "From Lab to Leadership". Explore her path from postdoc to platform builder.   Also this week:  – Phosphorylation’s selective role in β-arrestin recruitment across class B1 GPCRs  – GPCR mutations in cancer—drivers, passengers, or both?  – CXCR4 oligomer disruption boosts therapeutic response in lymphoid neoplasms Dr. GPCR Updates Learn Pharmacology That Drives Discovery  – From Dr. Terry Kenakin   Terry’s Corner is your space focused on GPCR pharmacology designed just for you.  Dr. Terry Kenakin brings translational clarity to complex receptor concepts.   This is more than review, it’s readiness. Learn binding, bias, kinetics, and core models—fundamentals that fuel confidence and fluency Move beyond theory to apply selectivity, ADME, and early safety in real development contexts Advance with nuanced lessons on allostery, residence time, and translational PK/PD   Subscribe to The Kenakin Brief Fluorescent Probe CELT-419 Powers D3R Binding Assays Across Platforms   Celtarys Research presents CELT-419, a nanomolar-affinity fluorescent ligand optimized for D3 receptor assays in both baculovirus and live-cell systems. With strong signal stability, HTS compatibility, and broad assay versatility, CELT-419 is designed for deeper kinetic, competitive, and equilibrium binding insights.    Explore Dr. GPCR Partner Tools The Story Behind Celtarys – From Chemistry to Company   How does a medicinal chemist become a biotech founder? This blog post breaks down Dr. Maria Majellaro’s path from lab research to co-founding Celtarys, as told in her recent Dr. GPCR Podcast appearance. Read how scientific need and timing drove the leap from academia to application.   Read the Story GPCR Publication Highlights     Phosphorylation selectively regulates β-arrestin recruitment  across glucagon family receptors, revealing that GLP-1R and GIPR rely on phosphorylation while GCGR does not.  GPCR mutations in cancer   show both driver-like patterns and high redundancy, prompting a call for multiomics to distinguish signal from noise.  CXCR4 oligomerization  sustains oncogenic signaling in lymphoid neoplasms, and its disruption boosts sensitivity to the apoptosis-inducing drug venetoclax. Want the full breakdown? Explore this week’s research, tools, and biotech insights in one place. Keep pushing the boundaries, because your work moves molecules and medicine forward.    Stay curious,   The Dr. GPCR Team

Watch Episode 168 Success in science is rarely linear. It’s a mosaic of risks, setbacks, and tiny wins that lead to clarity. Dr. Maria Majellaro’s story, shared in Episode 168 of the Dr. GPCR Podcast, is filled with such moments, from bombing her first high school chemistry test to co-founding a startup delivering tools for GPCR drug discovery. “The first time I wore my lucky cactus shirt to a major meeting... and it led to a game-changing collaboration.” — Dr. Maria Majellaro Maria didn’t always know she’d end up in a startup. In fact, her early decisions were based on curiosity, instinct, and a surprising love of cooking (yes, she even compares molecule design to perfecting focaccia). She studied pharmacy with a specialization in pharmaceutical chemistry, a degree that allowed her to see the full picture from synthesis to biology to formulation . Her turning points? Getting accepted into a PhD program during a personally difficult time. Saying yes to a postdoc opportunity abroad. Choosing not to overthink major career decisions, because as she puts it:  “A lot of friends of mine told me also, you already know what you want to do.” — Dr. Maria Majellaro Now, she leads a team of talented chemists at Celtarys, developing fluorescent ligands that help drug discovery teams better understand GPCR function. With the new  Dr. GPCR x Celtarys partnership , she’s extending those insights to researchers worldwide. 👉 Explore Celtarys’ tools and partnership with Dr. GPCR on the company page . _______________ Keyword Cloud:   GPCR scientist network , career development , fluorescent ligands , GPCR training program , Dr. GPCR ecosystem , GPCR podcast

Watch Episode 168 What does it take for a scientist to become a startup leader in biotech? For Dr. Maria Majellaro, the transition from lab work to leadership wasn’t meticulously planned, it was a bold leap fueled by gut instinct and a deep love for chemistry. In this episode of the Dr. GPCR Podcast, she shares how her background in medicinal chemistry paved the way to co-founding Celtarys , a company now shaping the future of GPCR assay tools. “I was good in the lab… but would I be good outside of it? That was the question I had to answer.” — Dr. Maria Majellaro Maria’s career didn’t start with a desire to launch a company. It began in Bari, Italy, with a love for science nurtured by her father and fueled by childhood cartoons about the human body. Over time, she developed a fascination with how molecules influence biology and how that chemistry could be applied in the drug discovery world. A postdoc in Santiago de Compostela introduced her to GPCRs, and from there, things escalated quickly. Celtarys was born out of necessity.  The academic group Maria worked with had developed a technology that allowed for flexible, fast synthesis of fluorescent ligands. However, as she and her co-founders soon realized, commercializing it was the only way to deliver that value to the broader GPCR research community. Celtarys Research, now partnering with Dr. GPCR, is helping researchers worldwide gain access to customized, reliable assay tools without the delays and frustrations that often plague probe development. 👉 Learn more about Celtarys’ science-driven solutions on their company page . _______________ Keyword Cloud:   GPCR drug discovery , GPCR research community , medicinal chemistry , Dr. GPCR ecosystem , GPCR online course , GPCR scientist network

Watch Episode 167 Today’s GPCR scientists don’t want to study one interaction, they want to model the network. In Episode 167, Dr. Sakmar reflects on a generational shift in training. The newest scientists want scalable, automated systems and the tools to move from data collection to insight . Building for the Future The Sakmar lab built a system to meet that need: Dual-epitope tagged constructs (N-term FLAG, C-term 1D4) Compatible with multiple readouts: proximity, immuno assays, pulldowns Validated antibodies + digital search platform Entire library hosted on Addgene This wasn’t a flash-in-the-pan project. It was structured, collaborative infrastructure . “The students of today want biosensors, miniaturization, and multiplexing. This delivers all three.” — Tom Sakmar A Use Case for Every Angle Beyond RAMPs, this platform can study: Scaffold protein interactions  (e.g., 14-3-3) Heterodimerization Endogenous vs. overexpressed systems Orphan GPCR deorphanization Ligand screening and functional validation Training the Next Wave Graduate students and visiting scientists are already expanding this work, bringing in computational layers  like AlphaFold to model GPCR-RAMP complexes in silico. Kotliar sums it up best: “We went from one receptor to many… and now, from many, we can go back to one, with purpose.” Listen to the complete episode to learn more. _________________ Keyword Cloud : GPCR scientist network , GPCR online course , GPCR data platform , multiplex assays , GPCR drug discovery

Watch Episode 167 Some GPCR-targeting antibodies don’t inhibit receptors. They activate them. This insight from Dr. Tom Sakmar points to a largely overlooked mechanism  in disease: autoantibodies that don’t block receptors but instead activate them , potentially driving pathology. From autoimmune disorders  to long COVID , we may be seeing just the tip of the iceberg. A New Role for GPCRs in Disease Sakmar highlights how endothelial cells, which express a wide array of GPCRs, are likely targets for antibody-based immune responses. And not all antibodies are created equal. “Some of these antibodies actually activate the receptor and cause pathological signaling.” — Tom Sakmar This makes them more than biomarkers — they’re potential drivers of disease . The Tools to Detect Them Using the multiplexed GPCR library and Luminex assay , researchers can now: Screen patient samples for GPCR autoantibodies Identify which receptor is being bound Determine if the antibody is activating or inhibitory Guide diagnostics or treatment research based on GPCR targets Beyond Classic ELISAs Traditional autoantibody testing relies on single-target ELISAs . Sakmar and Kotliar’s system is multiplexed and scalable , able to test hundreds of interactions from one tube of sample. What’s Next? Ilana Kotliar sees a future where this system is not just used for detection, but for functional screening : add ligands, track modulation, and even identify biased autoantibodies . This is the future of GPCR immunology . ________________ Keyword Cloud : GPCR autoantibodies , GPCR immunology , GPCR diagnostics , Dr. GPCR ecosystem , multiplex assays

Boston, MA and Santiago de Compostela, Spain — [June 3rd, 2025]  — Dr. GPCR, the global knowledge hub for G protein-coupled receptor (GPCR) research and education, is proud to welcome Celtarys Research to its partner ecosystem. This collaboration aims to amplify the visibility and adoption of Celtarys’ cutting-edge fluorescent ligand technology and accelerate the development of GPCR-targeted therapeutics. Celtarys Research develops high-quality, fluorescently labeled ligands and innovative chemical biology tools to support real-time, non-radioactive GPCR assays. These tools enable high-resolution binding studies, kinetic analysis, and live-cell imaging, empowering both academic and industrial scientists to uncover GPCR biology with greater precision and speed. As a Dr. GPCR partner, Celtarys will be featured across multiple touchpoints in the ecosystem, including the Dr. GPCR Newsletter , University Courses , and Podcast , as well as the searchable Dr. GPCR Ecosystem Directory —a centralized hub for tools, training, and technology. “We’re thrilled to partner with Celtarys and introduce their high-performance fluorescent ligands to our global GPCR community,”  said Dr. Yamina Berchiche , Founder and CEO of Dr. GPCR. “These tools can dramatically improve how scientists measure ligand-receptor interactions, visualize binding in live cells, and design better experiments, core to advancing GPCR-targeted discovery.” “Dr. GPCR provides a unique platform to reach scientists at every stage of GPCR research,”  said Wilson Gomes , CEO of Celtarys Research. “This partnership will help accelerate the adoption of our chemical tools and foster collaborations that turn receptor biology into therapeutic breakthroughs.” “We’re excited to support the GPCR community with tools that deliver clarity, sensitivity, and speed,”  added Dr. Maria Majellaro , CSO of Celtarys. “Working with Dr. GPCR allows us to engage with researchers worldwide who are shaping the future of receptor-targeted therapies.” To explore Celtarys Research’s catalog and learn more about their GPCR tools, visit  www.celtarys.com . For access to Dr. GPCR’s global network, educational content, and discovery tools, visit  ecosystem.drgpcr.com . ___________ About Dr. GPCR Dr. GPCR is a nonprofit organization connecting the global GPCR community through training, curated news, expert-led courses, and networking. With over 160 podcast episodes, live and on-demand educational programs, and a dynamic partner ecosystem, Dr. GPCR empowers scientists and companies advancing receptor biology and drug discovery. About Celtarys Research Celtarys Research is a biotech company based in Spain that specializes in the development of optimal chemical tools for drug discovery. Their proprietary chemistry platform enables rapid generation of conjugates, such as labeled ligands, with excellent affinity and pharmacological profiles, designed to advance GPCR-targeted assay development, screening, and live-cell imaging.

Watch Episode 167 What started with a single receptor became a toolset for an entire superfamily. Dr. Tom Sakmar didn’t set out to map GPCR-RAMP interactions across hundreds of receptors. In fact, it all began with a phone call (from Bruce Merrifield, no less) encouraging Sakmar to work on the glucagon receptor. That early curiosity around Family B GPCRs  set a 30-year trajectory in motion, culminating in a scalable, multiplexed platform to investigate GPCR-RAMP biology  like never before. A Long-Term Obsession, Reframed Sakmar’s lab had been focused on the secretin receptor family  for decades. But a question kept returning: How do RAMPs expand signaling diversity?  The key realization was that these small, single-transmembrane proteins weren’t just chaperones; they actively shaped receptor pharmacology . It was graduate student Emily Lorenzen  who helped frame the next step: stop studying one receptor at a time. With the help of Luminex technology and collaborators at SciLifeLab in Sweden , the lab built a multiplex assay  to study dozens of interactions simultaneously. “The beauty of multiplexing is that you can do many things with one pot of samples.” — Tom Sakmar Enter the Toolkit As the pilot data came together, rotation student Ilana Kotliar  joined and pushed the project to scale across all GPCR classes. What emerged was a dual-tagged GPCR library  (DUET constructs), now publicly available via Addgene , and an online platform to query GPCR-RAMP interaction data and antibody validations. These tools are already in use by labs around the world, with over 500 clone requests processed. Why It Matters This isn’t just a dataset, it’s a shift in how GPCR biology is approached : Study known & orphan GPCRs Identify new accessory protein interactions Build disease-relevant signaling models Validate antibodies for hard-to-study receptors And most importantly, it’s free to academics , built for the community. ________________ Keyword Cloud : GPCR-RAMP interactions , Family B GPCRs , GPCR scientist network , GPCR data platform , Dr. GPCR ecosystem

Hi GPCR Enthusiasts (and Arrestin Aficionados!)   This week at Dr. GPCR, we’re decoding arrestin-driven signaling and spotlighting the tools to match.   Check out our new on-demand course on non-canonical GPCR behaviors and a podcast episode tracing 30 years of GPCR-RAMP discovery. Additionally, new studies reveal how phosphorylation barcodes shape arrestin engagement, a biased NTSR1 modulator targets pain without the need for opioids, and a real-time lipid probe tracks early signaling events.   Significant insights—inside and out. Dr. GPCR Updates   Advanced Methods for the Optimization of Candidate Selection  – Master GPCR behavior beyond second messengers   Build sharper strategies for GPCR-targeted therapeutics with this advanced course—now available on demand for Premium members. Led by Dr. Terry Kenakin, these five modules reveal how location bias, intracellular signaling, and ligand kinetics can be leveraged to expand drug discovery horizons and fine-tune candidate selection.   Access the Course Hacking GPCRs: A Toolkit for Systems Biology – New Podcast Episode In Episode 167, Dr. Tom Sakmar and Dr. Ilana Kotliar share how three decades of curiosity evolved into a tech-powered platform for mapping GPCR-RAMP interactions. From dual-epitope tagging to scalable multiplex assays, this conversation dives deep into the tools now transforming receptor biology—and how they’re being used to de-orphanize GPCRs, explore autoantibodies, and uncover new therapeutic directions. GPCR Publication Highlights     GRK-Specific Phosphorylation Barcodes Shape Arrestin Engagement with ACKR3   A β-Arrestin-2-Biased NTSR1 Modulator for Non-Addictive Pain Relief   A Cell-Permeable Fluorescent Probe Illuminates Early PI(4,5)P₂ Dynamics at GPCRs Want the full breakdown? Explore this week’s research, tools, and biotech insights in one place.

Watch Episode 166 Early-career scientists often wrestle with impostor syndrome. Ben Clements has been there. But over time, he’s learned a skill that transformed his career: pacing. “Academia is about knowing when to walk and when to run.” This simple advice, passed on to Ben in grad school, has helped him stay sane, focused, and impactful. Running Too Hard, Too Fast In research, there’s always more to do. Grants. Experiments. Data analysis. Teaching. The pressure to stay productive never stops. But as Ben points out, burnout is real, and it doesn’t make you better. Some weeks, the best use of your time is reading, thinking, and slowing down. Other times, you’ll need to sprint. Knowing the difference is survival. Imposter Syndrome and Finding Your Place Ben shares the moment he realized he mattered, when he was the only one in the lab who knew how to do a particular injection in rats. Moments like these helped him own his identity as a scientist. A Final Aha Moment: Try the Crazy Idea When a collaborator offered a neuroma model (one where opioids usually fail), Ben took a chance. The result? A tenfold increase in methadone efficacy using PAMs. Sometimes, science rewards the bold. _________________ Keyword Cloud: GPCR online course, early-career scientists, imposter syndrome, GPCR podcast, neuroma model

Watch Episode 166 When’s the last time you argued in the lab about injecting GTPγS? Ben Clements has. And that moment, silly as it was, says a lot about how he sees science. Lab Culture Isn’t Just About Productivity Ben and his colleagues work hard in the lab. Four hundred plates of assays, concentration-response curves, and mutagenesis screens are standard. But every day also includes squirrel-themed trivia and impromptu debates about obscure molecules. Why? Because joy matters. “Science is fun. And we need that to do our best work.” – Ben Clements Mentorship Is the Engine of Science Ben chose his current postdoc lab for its people, not just the science. He was drawn to a team that balances rigor with levity, values mentoring, and encourages young scientists to speak up. When undergraduate students enter the lab, Ben doesn’t just teach them how to pipette, he teaches why they’re pipetting. And in doing so, he reminds himself to question assumptions, explain concepts clearly, and revisit the fundamentals. “Explaining pharmacology to a new student makes you relearn the basics. It sharpens everything.” What Makes a Great Scientific Home? • Leadership that supports academic career paths • A team that communicates under pressure • Space for curiosity, humor, and human connection For anyone searching for the "right" postdoc or PhD lab, this episode is a playbook for what to look for and what to build. _________________ Keyword Cloud: GPCR scientist network, GPCR training program, mentorship in science, GTPγS assay, lab culture

Watch Episode 166 Pain management is broken. And Benjamin Clements is on a mission to fix it. In this powerful episode of the Dr. GPCR Podcast, Ben, a postdoctoral fellow at the University of Michigan, walks us through how positive allosteric modulators (PAMs) targeting the mu-opioid receptor could preserve pain relief while reducing the devastating side effects of traditional opioids. Redefining Opioid Pharmacology Ben and his colleagues discovered that PAMs can dramatically increase the efficacy of existing opioids. In fact, one of their recent neuroma pain studies showed a tenfold increase in methadone potency. That’s not an incremental advance; that’s a potential paradigm shift. “We’ve seen these modulators rescue opioid function where it completely fails in neuroma models. That’s huge.” – Ben Clements By combining chronic pain models with receptor-level pharmacology, Ben is bridging molecule to model, and model to patient. His work highlights how foundational GPCR science can drive therapeutic innovation. Beyond Acute Pain: Into the Chronic Unknown Opioids work well for acute pain. Chronic pain? Not so much. Neuropathic conditions like neuromas often resist standard opioid treatments. Ben’s approach injects new life into an area most clinicians have given up on. Using PAMs, his team aims to re-sensitize these conditions to opioids without increasing toxicity. The GPCR Angle Ben sees GPCRs as untapped goldmines for drug discovery. Allosteric modulation is already proven in ion channels (think benzodiazepines and barbiturates) but still novel for GPCRs. And that’s where the excitement lies: "There’s so much space left to explore in GPCR-targeted modulation," he says. With collaborations across medicinal chemistry and neuropathic pain research, Ben is bridging molecule to model and molecule to patient. Ready to dive deeper into GPCR drug discovery? Want to push the boundaries of GPCR drug discovery? Start learning with our GPCR University today. _______________ Keyword Cloud: GPCR research community, GPCR drug discovery, mu-opioid receptor, positive allosteric modulators, GPCR training program, GPCR online course, GTPγS assay, chronic pain

Hello Sweet GPCR Enthusiasts, This week at Dr. GPCR: a new podcast episode with Dr. Ben Clements, a tour of our official Dr. GPCR Store, and a spotlight on the cryo-EM structure of the sweet taste receptor.   We’re also tracking biased signaling in Class B GPCRs, the membrane-driven modulation of mGluR2, and a big headline, Novo Nordisk’s $2.2B deal with Septerna to develop GPCR-targeted obesity therapeutics.  Scroll down for the science, the strategy, and the sweet stuff 🍬 Dr. GPCR Updates   New Podcast Episode  - When to Walk, When to Run with Dr. Ben Clements   In Episode 166, Ben Clements dives into opioid pharmacology, GPCR-targeted PAMs, and how old-school assays power breakthroughs. Tune in for sharp insights, tenfold gains in efficacy, and the wisdom of knowing when to walk and when to run. Wear Your Science – Dr. GPCR merch is here! Show off your receptor pride and support the mission. The official Dr. GPCR Store is live! Rock your favorite design, spark conversations in the lab, and help power everything we build—one mug or hoodie at a time. Visit the Store GPCR Publication Highlights   — The structure of human sweetness . A stunning cryo-EM structure of the sweet taste receptor (TAS1R2–TAS1R3) shows how aspartame and sucralose fit into a single, flexible binding pocket.   — Where are we now? Biased signalling of Class B G protein-coupled receptor-targeted therapeutics .  A comprehensive review walks us through the evolving clinical landscape of class B GPCRs—reminding us that precision pharmacology is here to stay.   — A tale of detergent tails: GPCR activation beyond ligands .  A new commentary highlights how detergents and cholesterol shape mGluR2 activation—no ligand required. A structural cautionary tale for all of us.  Want the full breakdown? Explore this week’s research, tools, and biotech insights in one place. From sugar-sensing structures to strategic partnerships—GPCRs remain at the center of it all. Best wishes, The Dr. GPCR Team