SGC0946 (trifluoroacetate salt)

SGC0946 is an inhibitor of the non-SET domain-containing methyltransferase DOT1L (IC50 = 0.3 nM). It is selective for DOT1L over a panel of 12 additional protein methyltransferases, DNA methyltransferase 1 (DNMT1), and a panel of 29 receptors and ion channels. SGC0946 reduces the levels of dimethylated lysine 79 on histone 3 (H3K79me2) in MCF-10A breast cancer cells (IC50 = 8.8 nM). It selectively reduces the viability of isolated human cord blood cells transformed with an MLL-AF9 fusion oncogene over those transformed with a TLS-ERG fusion oncogene when used at concentrations of 1 and 5 µM. Adoptive transfer of isolated human CD3+ T cells pre-incubated with SGC0946 (0.5 µM) prevents weight loss, increases survival, and reduces hepatic and colonic lymphocyte infiltration in a xenogeneic mouse model of graft versus host disease (GVHD).Formal Name: 5-bromo-7-[5-deoxy-5-[[3-[[[[4-(1,1-dimethylethyl)phenyl]amino]carbonyl]amino]propyl](1-methylethyl)amino]-beta-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine, trifluoroacetate salt. Molecular Formula: C28H40BrN7O4 . XCF3COOH. Formula Weight: 618.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Slightly soluble: 0.1-1 mg/ml, Ethanol: Sparingly soluble: 1-10 mg/ml. SMILES: CC(C)(C)C1=CC=C(NC(NCCCN(C(C)C)C[C@@H]2[C@@H](O)[C@@H](O)[C@H](N3C(N=CN=C4N)=C4C(Br)=C3)O2)=O)C=C1.O=C(O)C(F)(F)F. InChi Code: InChI=1S/C28H40BrN7O4.C2HF3O2/c1-16(2)35(12-6-11-31-27(39)34-18-9-7-17(8-10-18)28(3,4)5)14-20-22(37)23(38)26(40-20)36-13-19(29)21-24(30)32-15-33-25(21)36,3-2(4,5)1(6)7/h7-10,13,15-16,20,22-23,26,37-38H,6,11-12,14H2,1-5H3,(H2,30,32,33)(H2,31,34,39),(H,6,7)/t20-,22-,23-,26-,/m1./s1. InChi Key: APFJHYFYYBZVJX-DGUBOJIQSA-N.