Insights That Move the GPCR Field Forward

Most GPCR programs don’t fail because of weak molecules—they fail because biology behaves differently than the assay implied. This week’s feature goes straight to the foundation: how system-level GPCR thinking protects discovery teams from the costly misinterpretations that derail programs. If your work touches GPCR pharmacology, these insights aren’t optional—they’re essential.

Most pharmacologists are trained to chase targets. But what if the real opportunity lies in the chemical matter we throw at them? That’s exactly what Terry’s Corner delivers this week: a deep dive into molecular creativity, rational design, and the overlooked role of chemistry in innovation. Breakthroughs this week: Orphan receptor GPRC5B in neurogenesis; Septerna’s pill-based weight-loss strategy; Atrogi’s new CEO announcement.

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.