{"candidate_id":"rly2608-pik3ca","display_id":null,"title":"RLY-2608 (mutant-selective allosteric PI3Ka) × PIK3CA","question":"RLY-2608 (mutant-selective allosteric PI3Ka) × PIK3CA","targets":["PIK3CA"],"biomarkers":["PIK3CA H1047R","PIK3CA E545K"],"public_status":"evidence_supported","validation_ready":true,"priority_score":0.5,"kind":"target_strategy","evidence_refs":["pubchem:166822065","Varkaris AACR 2023 — RLY-2608 mutant-selective PI3Ka","Cancer Discov 2024 RLY-2608"],"content_hash":"517e8ac311b96f9db32cd2445ce792f94bd973ff","updated_at":"2026-07-07","mechanism":"Mutant-selective allosteric inhibition of PI3Ka (H1047R/E545K), sparing wild-type.","rationale_md":"Concrete instantiation of the director's allele-specific PI3Ka frontier bet. RLY-2608 is a real mutant-selective allosteric PI3Ka inhibitor. Docking falsifies reversible engagement of the redock-verified PIK3CA/4JPS pocket only (non-covalent; does not score bond formation)."}