PEP08

PEP08 is a novel, highly selective small molecule inhibitor targeting protein arginine methyltransferase 5 (PRMT5) in an MTA-cooperative fashion. It is specifically designed to exploit the vulnerability of MTAP-deleted cancers by forming a stable ternary complex with PRMT5 and accumulated MTA, selectively killing MTAP-null tumor cells while sparing normal cells. PEP08 exhibits central nervous system (CNS) penetration and has demonstrated efficacy in multiple MTAP-deleted tumor xenograft models, including those of glioblastoma (GBM). It is currently in first-in-human clinical trials for advanced or metastatic solid tumors with MTAP deletions. The compound is being developed by PharmaEngine[1][2][3][4][7][10].