Target Protein A: Hit Triage

You are the lead medicinal chemist on a first-in-class drug discovery project against Protein A. There is no published small-molecule chemical matter against this target.

Your team screened a commercial library of 200,000 compounds in a biochemical assay with a hit cutoff of IC50 < 50 µM. Four compounds confirmed in repeat biochem at low-micromolar potency.

You just received orthogonal SPR (surface plasmon resonance) data on those four hits to test whether they bind Protein A directly. Inspect each hit, calculate the properties and structural alerts, and decide which to advance or kill before the team meeting tomorrow.