The Off-Rate Nobody Measured

July 22
2h 13m

Episode Description

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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