Breaking the Myth of High and Low Affinity Sites

Terry's Desk
Jul 15
2 min read

Updated: Aug 11

The Affinity Illusion: Rethink Efficiency

Kenakin’s Emerging Drug Hunter lecture delivers exclusive, cutting-edge insights that help you move beyond outdated assumptions and equip your team to interpret data with clarity and confidence.

In this session, you’ll gain:

✅ A framework for understanding when apparent multiple affinities really matter—and when they don’t

✅ Guidance on extracting meaningful information from binding experiments that advance your work efficiently

✅ Clarity that helps you move from assay to decision faster, with fewer false starts

This isn’t textbook material—it’s real-world expertise designed to help you optimize faster and more effectively.

Move Faster, Smarter, and with Confidence

When you understand what your assays are truly showing you, you eliminate wasted effort and focus only on compounds with genuine potential.

Every day spent misunderstanding the meaning of apparent affinity differences can slow your project’s path to key milestones.

This is about accelerating your path from discovery to clinic, without wasted cycles or missteps.

Why the Myth of High and Low Affinity Binding Sites Could Be Slowing Your Pipeline

If you’re working in drug discovery, you know the pressure: timelines are tight, resources finite, and decisions must be fast and informed. Yet some assumptions still shaping pharmacology workflows haven’t evolved as fast as today’s science.

One of the most persistent misconceptions? The interpretation of high and low affinity binding sites on GPCRs.

At first glance, when a ligand appears to bind at two different affinities in the same system, it seems logical to assume two distinct sites. But as Terry Kenakin reveals, this interpretation can be misleading, and sticking with it could slow your path to an optimized candidate.

High and Low Affinity: What’s Really Going On?

It’s common to observe two apparent affinities for a ligand under certain experimental conditions. But are these differences really pointing to two physical sites?

Kenakin challenges this assumption and shows that what you’re seeing may reflect something entirely different.

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.

But this doesn’t necessarily reflect what’s happening in a physiological context, and misunderstanding this can introduce inefficiency into your decision-making process.

Are You Using Models That Slow You Down?

The analytical tools that shaped traditional affinity analysis were designed for simpler systems. Without appreciating their limitations, it’s easy to misinterpret affinity values, potentially leading to inefficient workflows.

Misunderstandings at this level can delay optimization cycles, result in wasted SAR iterations, or cause programs to focus on leads that won’t deliver—ultimately slowing your program’s forward momentum.

Don’t let outdated interpretations slow your next program. Join Now — Access Immediate, Actionable Insight

You’ll gain the insight needed to:

Interpret complex binding data correctly
Separate what matters from what misleads
Make confident, efficient decisions that keep your pipeline moving forward, toward your next milestone.