GSK3685032

A DNMT1 inhibitor (IC50 = 0.23 µM), selective for DNMT1 over DNMT3A/3L and DNMT3B/3L and a panel of 34 methyltransferases and 369 kinases (IC50s = >10 µM for all), inhibits the proliferation of 51 hematological cancer cell lines (median IC50 = 0.64 µM), decreases overall DNA methylation and gene expression in MV4-11, THP-1, and NOMO-1 cells in a time- and concentration-dependent manner, increases the expression of genes encoding CXCL11, IFI27, and MAGEA4, 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 at 45, 30, or 15 mg/kg twice per day. Formulation: A solid. 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)/t19-/m1/s1. InChIKey: KNKHRZYILDZLRE-LJQANCHMSA-N. SMILES: N#CC1=C(N=C(S[C@H](C2=CC=CC=C2)C(N)=O)C(C#N)=C1CC)N3CCC(N)CC3