GSK3235025

GSK3235025, also known as EPZ015666, is a potent, selective, and orally bioavailable small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), with an IC50 of 22 nM and a Ki of 5 nM. Developed through a collaboration between Epizyme and GSK, it serves as a critical chemical probe for studying the role of PRMT5 in epigenetic regulation and oncogenesis. The compound works by binding to the PRMT5:MEP50 complex in a substrate-competitive manner, effectively blocking the symmetric dimethylation of arginine residues on both histone and non-histone proteins. In preclinical studies, GSK3235025 has demonstrated significant dose-dependent antitumor activity in xenograft models of mantle cell lymphoma (MCL). Its high selectivity (>20,000-fold over other methyltransferases) makes it a valuable tool for validating PRMT5 as a therapeutic target in various malignancies, including hematological and solid tumors.

Other names

(S)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide