LLY-283

LLY-283 is a potent and selective small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), developed through a collaboration between Eli Lilly and the Structural Genomics Consortium. It is a SAM-competitive inhibitor that blocks PRMT5's enzymatic activity, with low nanomolar IC50 values in both biochemical and cellular assays, and demonstrates pronounced selectivity over other methyltransferases and epigenetic targets. LLY-283 has shown significant antitumor activity in multiple preclinical cancer models, including brain-penetrant activity and radiosensitization in glioblastoma, as well as protection against noise-induced hearing loss via attenuation of reactive oxygen species and activation of the PI3K/AKT pathway. Its utility as both a chemical probe and a potential therapeutic candidate for oncology and other indications is supported by its robust preclinical profile, though it remains in preclinical or early evaluation stages with no approvals to date.[1][2][3][4][5][7][8][9][11][12][13]