AN9025

AN9025 is an orally bioavailable small molecule pan-RAS(ON) inhibitor developed by Adlai Nortye. It is designed to target a broad spectrum of RAS mutations across multiple tumor types, including pancreatic adenocarcinoma, lung adenocarcinoma, and colorectal adenocarcinoma. Preclinical studies have demonstrated that AN9025 efficiently inhibits RAS-mutant cancers with potent and durable efficacy, showing comparable or superior results relative to benchmark agents in the same class. Mechanistically, it forms a tri-complex with cyclophilin A (CypA) and RAS proteins to block downstream signaling pathways critical for tumor growth. Notably, it has shown activity in cell models resistant to KRAS(OFF) G12C inhibitors such as sotorasib and adagrasib but does not affect BRAF-mutant or RAS-independent cell lines. The drug is currently in preclinical development with plans for IND submission in the second half of 2025[1][2][3][4][5][6][7].