IDE892

IDE892 is a potent and selective methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor developed by IDEAYA Biosciences for the treatment of solid tumors, particularly those with MTAP (methylthioadenosine phosphorylase) deletions. The drug was discovered using an iterative physics-based ligand design and optimization platform, resulting in a compound with favorable potency, selectivity, and drug-like properties. Preclinical studies have demonstrated that IDE892 exhibits robust antiproliferative activity specifically in MTAP-deleted tumor cell models and achieves durable complete responses when combined with the MAT2A inhibitor IDE397. The mechanism leverages synthetic lethality between PRMT5 inhibition and MTAP deletion to selectively target cancer cells while sparing normal tissue. IND-enabling studies are ongoing as of early 2025, with plans to initiate clinical trials for non-small cell lung cancer and urogenital cancers in combination therapy settings[1][2][3][4][5][8].