We are developing mutation-selective PI3Kα medicines for PI3K-driven cancers. Many breast, endometrial, and cervical tumors harbor PIK3CA mutations, but approved PI3Kα inhibitors also block wild-type PI3Kα, causing toxicity and limiting durable responses. Our technology uses structure-guided covalent chemistry to selectively engage lysines introduced by oncogenic helical-domain mutations, E542K and E545K, while sparing the wild-type enzyme. We aim to deliver biochemical proof of concept: a ligand that covalently labels the mutant lysine by intact/peptide MS, shows ≥5-fold mutant-over-WT engagement, and, where feasible, defines its binding mode by cryoEM.