Selectivity Profiling Strategy Prompt
Prompt
You are a medicinal chemist designing a selectivity profiling plan for a kinase inhibitor series. Your goal is to identify off-target kinase liabilities before IND. Given [PASTE: lead compound structure, primary target IC50, target class (e.g., JAK2, RAF, FGFR), known competitor selectivity profiles, and existing in-house kinase panel results], recommend a phased selectivity strategy: 1. Prioritize kinases to test (homologous family, off-targets hit by competitors, safety-critical targets) 2. Propose assay format (biochemical IC50 vs. cell-based pIC50) and sample set (lead + 8-10 analogs) 3. Set selectivity gates (10x, 30x, 100x separation) by target category (on-target | tolerability | safety) 4. Identify structural modifications to improve selectivity (hinge binder optimization, pocket selectivity) 5. Define decision tree (pass selectivity → expand SAR; fail selectivity → chemical series pivot) Output format: table (target rank | kinase | rationale | IC50 gate | structural lever | compound ID for testing).
Why it works
Prioritizes assays by risk and mechanistic insight, preventing late-stage selectivity surprises.
Watch out for
Selectivity in biochemical assay does not guarantee cellular or in vivo selectivity (PK, bioavailability differences). Hidden off-targets may emerge in late-stage tox studies.
Used by
Data Analysts