LLY-283 is an inhibitor of protein arginine methyltransferase 5 (PRMT5; IC50 = 22 nM).1 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.2 See the Structural Genomics Consortium (SGC) website for more information.
1.Bonday, Z.Q., Cortez, G.S., Grogan, M.J., et al.LLY-283, a potent and selective inhibitor of arginine methyltransferase 5, PRMT5, with antitumor activityACS Med. Chem. Lett.9(7)612-617(2018) 2.Sachamitr, P., Ho, J.C., Ciamponi, F.E., et al.PRMT5 inhibition disrupts splicing and stemness in glioblastomaNat. Commun.12(1)979(2021)