Drug discovery often assumes receptor inhibition follows simple rules—agonist binds, antagonist blocks, and data fit neatly into predictable curves. Yet, any pharmacologist who’s pushed beyond textbook theory knows: biology rarely plays fair. Schild analysis remains one of the few conceptual anchors that can tell us when “simple” truly is simple—and when deeper receptor dynamics are at play.

Drug discovery pipelines often stall not because the target is wrong—but because the chemical matter interacting with that target lacks the right properties to produce meaningful pharmacology. We obsess over target validation, signaling pathways, expression patterns, and disease relevance. Yet, far less time is spent scrutinizing the structural logic and origin of the molecules we screen in the first place.

Nine out of ten GPCR programs stall not because the target was wrong, but because teams waited too long to test the right thing. Terry Kenakin has seen this story play out for 40 years — and he’s rewriting the ending.

This session unpacks how persistent binding can either accelerate your program—or quietly kill it. That’s the power (and the peril) of irreversible drugs. These aren’t just “stronger binders.” They’re kinetic game-changers—compounds that rewrite the relationship between ligand, receptor, and physiologic outcome. Understanding how persistent binding affects receptor turnover, tissue penetration, and PK/PD relationships can give your team a strategic edge.

Before your GPCR ligand ever meets its receptor, it meets the enzymes that determine whether it survives long enough to act. Recognizing, predicting, and leveraging these interactions is the essence of enzyme inhibition pharmacology—the framework that connects molecular survival to clinical success.

Every delay in the discovery pipeline compounds into wasted years, lost opportunities, and soaring costs. For drug hunters working at the GPCR interface, the difference between a successful lead and a dead-end candidate often comes down to one overlooked factor: system sensitivity and how we control it.

The difference between orthosteric vs. allosteric mechanisms isn’t just academic — an orthosteric antagonist can hijack receptor physiology, while an allosteric modulator works with the system. That choice determines whether you risk over- or under-dosing, miss safety windows, or miss therapeutic breakthroughs.

GPCRs don’t play fair. Learn how opposing processes, receptor trafficking, and constitutive activity shape drug response—and how to design for them.

Learn how ligand binding kinetics reveal hidden drug effects, improve GPCR assay design, and prevent costly errors in drug discovery pipelines.

Turn assay snapshots into predictions. Models separate orthosteric vs allosteric mechanisms and guide experiments for faster decisions in Terry’s Corner.

Stop guessing at curve shifts. Learn how t-tests, ANOVA & F-tests bring confidence, not noise, to drug discovery decisions.

Think you understand ligand displacement? Think again. This week’s Terry’s Corner blog reveals how allosteric modulators reshape receptor identity—and why conventional binding logic fails in these systems.

Most drug discovery teams chase potency, but miss the variable that often determines real-world success: target residence time. In this expert lecture, Dr. Terry Kenakin explores how restricted diffusion, rebinding, and kinetic dissociation transform in vivo pharmacology, especially when PK and PD diverge. If your leads fail in translation, this may be the insight your pipeline needs.

Don’t let curve shapes deceive you. In this blog, Dr. Terry Kenakin unpacks why dose-response shifts aren’t definitive proof of antagonist mechanism. Learn how binding kinetics—not just appearance—distinguish competitive from non-competitive antagonism, and why assumptions can mislead drug discovery decisions. If your team relies on DR curves to evaluate receptor blockade, this read will sharpen your approach and help you avoid common pitfalls in mechanism interpretation.

From cryptic binding sites to ligand‑specific signaling, uncover how GPCR dynamics redefine drug discovery strategies and decision‑making.

Explore how GPCRs function as dynamic allosteric machines in this expert-level breakdown from Dr. Terry Kenakin. Learn how probe dependence, cryptic binding sites, and conformational changes impact drug discovery and therapeutic design.

Kenakin’s kinetic insights help you translate assay readouts into actionable knowledge that keeps your programs focused and moving efficiently toward clinical relevance.

In Terry Kenakin’s latest lecture from the Emerging Drug Hunter series, he invites you into a thought-provoking reevaluation of one of pharmacology’s most misleading concepts: the myth of high and low-affinity binding sites.

In Terry Kenakin’s latest foundational lesson from Terry’s Corner, he unpacks the art and science of pharmacologic modeling. This isn’t just theory—it's the essential framework used to interpret experimental data, anticipate system-wide drug effects, and design smarter trials.

In this lesson, Terry Kenakin dismantles 100 years of receptor theory and introduces you to a dynamic new framework: Molecular Dynamics. Discover how receptors actually behave, how ligands uniquely sculpt their function, and how cryptic allosteric sites are quietly reshaping the frontier of drug discovery.

In this eye-opening module, Terry Kenakin explores a concept that could change how you interpret pharmacological data: the interplay between intrinsic efficacy and system sensitivity. It’s not just about what your molecule does—it’s also about how capable your system is at showing it.

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.

In this foundational lesson, Terry Kenakin dives deep into a widely used, often misunderstood tool in early drug discovery: the calcium assay. Revered for its convenience, the FLIPR assay provides rapid insights into receptor activity. But its speed comes with a cost.

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.