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In This Session, You’ll Gain: ✅ Modeling tools to understand how restricted diffusion  in tissues like Kenakin walks through cases where two equipotent ligands produce radically different clinical outcomes And when receptors are dense (like GPCRs on membranes), this rebinding hits the collisional limit , where Why Half-Life Can Lie to You Most teams use systemic half-life as a proxy for action. Terry Kenakin Monthly Ask‑Me‑Anything sessions with live Q&A An expanding on‑demand library for novices

—Alessandro Nicoli This two-way growth has turned mentoring into one of his favorite parts of PhD life

Watch Episode 171 What happens when your protein has no known ligands, no structure, and very little The Problem: Hundreds of Receptors, Almost No Ligands Alessandro’s work focuses on olfactory GPCRs—nearly Most have only one known ligand, if any. That meant simulations, ligand screening, and experimental design could move forward with confidence. More accurate hypotheses, faster ligand discovery, and new strategies to tackle one of biology’s most

At first glance, when a ligand appears to bind at two different affinities in the same system, it seems It’s common to observe two apparent affinities for a ligand under certain experimental conditions. In many systems, a ligand may appear to bind with very high affinity when it facilitates formation of ligand-receptor-G protein complexes —an observation that creates the illusion of multiple sites.   Without appreciating their limitations, it’s easy to misinterpret affinity values, potentially leading

Same Affinity, Different Outcomes: Why Residence Time Matters More Two ligands. balance between lipid and aqueous environments.   And while orthosteric ligands may never reach them, properly designed intracellular drugs can. Persistent binding isn’t just about longer half-lives—it’s about smarter pharmacology. Terry Kenakin Monthly Ask‑Me‑Anything sessions with live Q&A An expanding on‑demand library of past lessons

more nuanced, and mastering drug binding kinetics is essential for pipeline efficiency: How fast a ligand Competitive conditions —such as the presence of endogenous ligands— change kinetic behavior , and ignoring Kinetic measurements reveal hidden liabilities or advantages that static affinity numbers cannot. How do competing ligands slow or alter binding rates, and what does this tell you about real-world pharmacology Without appreciating their limitations, it’s easy to misinterpret key kinetic signals that matter for

Listen Now – Real Lessons from a GPCR Expert ➤ The future of GPCR isn’t waiting.

CRCM Must-read publications : AlphaFold3 benchmarking for GPCRs; new structural insights into peptide ligand At first glance, when a ligand binds at two different affinities in the same system, it seems logical If you’re not accounting for their limitations today, your team risks costly misinterpretations that Katerina Leftheris : New technologies overcoming peptide limitations with insights from both pharma and and team fit—not just credentials Design workflows that enable curiosity-driven research Support work-life

Allostery isn’t just an advanced concept—it’s essential to understanding efficacy, ligand bias, and receptor As the GPCR field surges forward—from ligand bias to signaling diversity—the guest editors Dr. Why you need to be there: Learn how kinetic nuance shapes ligand design.   Access peer insights on allosteric modulators and biased ligands. GPCR Podcast Listener Why Dr.

Breakthroughs this week: Glucagon-like Peptide-1 Receptor (GLP-1R) Signaling; Proximity-Dependent Proteomics But what if the most significant opportunities lie just inside the cell membrane? This week Dr. Learn how his research aims to develop models that can distinguish between active and inactive ligands , paving the way for computational ligand discovery even where experimental data is scarce. " targets, like olfactory receptors, accessible for computational analysis.

The Early Days: Molecules and Mentors Alessandro began his academic life studying pharmaceutical chemistry every day the results, I was getting in love with the topic and decided—yeah, I want to do this in my life With hundreds of subtypes and limited ligand data, olfactory GPCRs represent a high-risk, high-reward

and then conjugated with a fluorescent ligand. Fluorescent ligands provide real-time data on receptor activation, ligand binding and downstream signaling using live-imaging modalities. The dashed line represents the frontier between both cell types. Fluorescent ligands: Bringing light to emerging GPCR paradigms.

This approach reflects his focus on developing models that behave  like patients before molecular exploration hypothesis, Serafini’s team noticed that hamsters infected with SARS-CoV-2 exhibited persistent pain-like This patient-centric and behavior-first approach uncovered robust gene expression signatures  linked He also integrates concepts like sex differences , epigenetic inheritance , and neuroimmune crosstalk

. 👉 Dive into Terry’s Vault and see agonism like never before Unlock "Agonism & Sensitivity" now

Through real-world examples (like 5-HT2A and CCR5 agonists), Terry shows how slow-onset agonists can Because when true pharmacological profiling is essential—like detecting partial or inverse agonism—calcium

into clinical forecasts The 4 types of pharmacologic models (and when to use each) The truth about linear How the Mass Action Law underpins nearly every model Future of Receptor Theory: Linkage vs.

Serafini described his connection to GPCRs as tangential but inevitable: "I feel like I never was particularly 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 The real power may lie in how they’re regulated. Dr.

Terry Kenakin’s featured talk on “The Kinetics of Allostery” offers a rare live glimpse into advanced Identify emerging targets:  Allosteric modulators, biased ligands, and kinetic frameworks will dominate

After years of living with unresolved pain following surgery for a pilonidal cyst, Alex was left without This is a story about how chronic pain doesn't just shape lives — it reshapes careers. The Value of Lived Experience in Science What makes Serafini’s trajectory so compelling isn’t just his His interest in model development, in capturing the lived human experience through preclinical systems He’s focused on RGS proteins , pain comorbidities  like addiction and depression, and pushing for more

By considering factors like the Langmuir adsorption isotherm and binding curves, researchers can better

These ongoing conversations keep me on the front lines, sharpening my understanding of the common bottlenecks

recovering from a stall, I’ll help you move faster—with fewer blind spots, tighter execution, and a clear line

But Sokhom Pin stayed loyal to GPCRs , even when big pharma turned its gaze to other targets like kinases High-throughput screening for receptor ligands was booming, and Sokhom was at the center of it.

just credentials He designed lab workflows that encouraged curiosity without burnout He supported work-life In a field like GPCR research (where data complexity and failure rates are high), scientific rigor thrives Alkermes didn’t just improve drug screening outcomes, it redefined what great leadership in biotech looks like

As a lab technician at Johns Hopkins, he was fascinated by science but also grounded in real-life responsibilities Takeaway If you’re navigating work, life, and scientific ambition, Sokhom Pin proves it’s possible to

Welcome Back, Discovery Drivers   Terry’s Corner is live, on-demand pharmacology built for drug discovery Dr.GPCR Updates Terry’s Corner is Live - Pharmacology at your fingertips Terry’s Corner is now open! Join Terry’s Corner Today Yamina’s Corner Is Live – Are you drowning in disorganized data? GPCR partner Celtarys Research has validated a TR-FRET assay for cannabinoid receptor ligands using their Distinct Ligand Activation in NMBR Simulations show how two ligands differently activate class A GPCR

During that project we tested its validity as a fluorescent probe for Tag-lite® assays, where we used a set of 7 cannabinoid ligands (both natural and synthetic) to validate and optimize the assay. Because Tag-lite® is based on FRET, we have collaborated with BMG Labtech to develop an application note In this case, Terbium is used as donor and CELT-335 fluorescent ligand is used as acceptor. FSX is the ideal microplate reader for characterizing the GPCR-ligand interactions.

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.   Sign Up for The Kenakin Brief Fluorescent Ligands vs. Radioligands – Assay Smarter Celtarys explores how fluorescent ligands enable safer, high-throughput

Ever wondered why a drug behaves like a miracle in one tissue and a dud in another?

What happens between identifying a target and delivering a life-saving treatment? In this foundational-level  lesson, Terry unpacks the real-life process behind discovering new drugs,