2040291-27-6

LLY-283 is an inhibitor of protein arginine methyltransferase 5 (PRMT5; IC₅₀ = 22 nM). It is selective for PRMT5 over a panel of methyltransferases, including PRMT4, -6, and -7 at 1 μM. It reduces symmetric demethylation of SmBB'' in MCF-7 cells (IC₅₀ = 25 nM) and inhibits proliferation of various breast, gastric, hematological, lung, skin, and ovarian cancer cell lines (IC₅₀s = 3-30 nM). LLY-283 (20 mg/kg) inhibits tumor growth in an A375 mouse xenograft model. It also disrupts alternative splicing events in, and inhibits proliferation and self-renewal of, patient-derived glioblastoma stem cells and increases survival in an orthotopic patient-derived xenograft (PDX) mouse model. See the Structural Genomics Consortium (SGC) website for more information.

LLY-283 is a potent, selective and oral protein arginine methyltransferase 5 (PRMT5) inhibitor, with an IC50 of 22 nM and a Kd of 6 nM for PRMT5:MEP50 complex, and shows antitumor activity.

PRMT5

[1] Zahid Q. Bonday, et al. LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity. ACS Med. Chem. Lett., 2018, 9 (7), pp 612-617.