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

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

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.