(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5[(R)-hydroxy(phenyl)methyl]tetrahydrofuran-3,4-diol

Description

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.