Insights That Move the GPCR Field Forward

Discovery programs rarely fail because a molecule “did nothing.” They fail because a molecule behaved exactly as the underlying system allowed—amplified, buffered, redirected, or reshaped by layers of receptor biology that weren’t accounted for. The October 30th AMA with Dr. Kenakin highlighted a fundamental truth: GPCR systems do not offer stable, proportional input–output relationships. Receptor density, constitutive activity, coupling efficiency, local signaling archit

Every drug you design will meet an enzyme before it meets its receptor. If you want your molecules to survive first contact with biology—and with the FDA—enzyme inhibition must be part of your core playbook. This week’s feature breaks down exactly how to think about inhibitors with rigor and speed, so you can make better decisions earlier in the pipeline. Breakthroughs this week: Potentiation of GPCR signaling by ATP and sugar monophosphates; Pharmacology 2025; Nxera Pharma

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.