Same binding affinity. Same target. One compound worked in vivo. The other did nothing. The answer was how long each molecule stayed on the CRF receptor — seven hours versus fifteen minutes — and no one had thought to measure it.
Sam Hoare spent 15 years at Neurocrin Biosciences before founding PharmaChanics, a pharmacology data analysis consultancy built on one conviction: most GPCR teams are collecting data they don't know how to analyze. In this conversation, Hoare walks through the off-rate discovery that redirected an entire drug program, the signaling kinetics framework he developed to fill a gap no one had formally acknowledged, and what it actually takes to move from industry scientist to independent consultant. Along the way: why GPCRs are the most tractable system in pharmacology — and why that still isn't enough if the analysis is wrong.
How receptor residence time — not affinity — determined which CRF compound reached Phase 2
Why time-course signaling data is routinely collected but almost never analyzed with the rigor applied to dose-response curves
What 15 years of GPCR drug discovery taught Hoare about the gap between understanding a receptor and making a drug for it
How early-career researchers can leverage deep target expertise to build a consulting practice
The three aha moments that have kept a pharmacological data analyst motivated across a 30-year career
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