H3B-8800

An inhibitor of the SF3B complex, binds to SF3B complexes containing wild-type SF3B (IC50 = 1.4 nM) or various SF3B mutations (IC50s = 0.3-1.8 nM), inhibits SF3B1-induced splicing of canonical and aberrant pre-mRNA junctions in HEK293T nuclear extracts overexpressing SF3B1K700E, selectively inhibits the growth of, and induces apoptosis in, Panc 05.04 pancreatic cancer cells expressing mutant SF3B over Panc 10.05, HAPF-II, and CFPAC-1 pancreatic cancer cells expressing wild-type SF3B in a concentration-dependent manner, reduces tumor growth in a K562 mouse xenograft model using K562 cells expressing wild-type SF3B1 at 8 mg/kg and K562 cells expressing SF3B1K700E at 2, 4, or 8 mg/kg. Formulation: A solid. InChI: InChI=1S/C31H45N3O6/c1-22(26-11-6-7-16-32-26)9-8-10-23(2)29-24(3)12-13-27(39-30(37)34-19-17-33(5)18-20-34)31(4,38)15-14-25(35)21-28(36)40-29/h6-13,16,22,24-25,27,29,35,38H,14-15,17-21H2,1-5H3/b9-8+,13-12+,23-10+/t22-,24+,25-,27+,29-,31-/m1/s1. InChIKey: YOIQWBAHJZGRFW-WVRLKXNASA-N. SMILES: O=C(N1CCN(CC1)C)O[C@H]2/C=C/[C@@H]([C@H](OC(C[C@@H](CC[C@]2(O)C)O)=O)/C(C)=C/C=C/[C@H](C3=CC=CC=N3)C)C