GSK3685032

GSK3685032 is an inhibitor of DNA methyltransferase 1 (DMNT1, IC50 = 0.23 µM). It is selective for DMNT1 over DMNT3A/3L and DMNT3B/3L and a panel of 34 methyltransferases and 369 kinases (IC50s = >10 µM for all). GSK3685032 inhibits the proliferation of 51 hematological cancer cell lines (median IC50 = 0.64 µM). It decreases overall DNA methylation and gene expression in MV4-11, THP-1, and NOMO-1 acute myeloid leukemia (AML) cells in a time- and concentration-dependent manner. GSK3685032 increases the expression of the genes encoding chemokine (C-X-C) motif ligand 11 (CXCL11), IFN-alpha-inducible protein 27 (IFI27), and melanoma-associated antigen 4 (MAGEA4). In vivo, GSK3685032 (45, 30, or 15 mg/kg twice per day) reduces tumor volume and increases survival but does decrease blood numbers of neutrophils and red blood cells in SKM-1 and MV4-11 leukemia mouse xenograft models. InChI: InChI=1S/C22H24N6OS/c1-2-16-17(12-23)21(28-10-8-15(25)9-11-28)27-22(18(16)13-24)30-19(20(26)29)14-6-4-3-5-7-14/h3-7,15,19H,2,8-11,25H2,1H3,(H2,26,29) InChIKey: KNKHRZYILDZLRE-UHFFFAOYSA-N SMILES: N#CC1=C(N2CCC(CC2)N)N=C(C(C#N)=C1CC)SC(C(N)=O)C3=CC=CC=C3