MRTX9768

**MRTX9768** is a preclinical, orally bioavailable, first-in-class **small-molecule inhibitor of the PRMT5-MTA complex** developed by **Mirati Therapeutics** for cancers harboring **MTAP deletion**, including tumors with concomitant **MTAP/CDKN2A loss**. The compound was discovered using a fragment-based approach and is designed to selectively bind and stabilize the catalytically inactive **protein arginine methyltransferase 5-methylthioadenosine complex**, thereby exploiting a synthetic lethal vulnerability in MTAP-deleted tumor cells while largely sparing MTAP-wildtype cells. Preclinical data presented in 2021 showed selective antitumor activity in MTAP-deleted models, supporting its positioning as a targeted antineoplastic epigenetic therapy.