GNE-781

GNE-781 is an inhibitor of CREB-binding protein (CBP) and histone acetyltransferase p300 (IC50s = 0.94 and 1.2 nM, respectively). It is selective for CBP and p300 over bromodomain-containing protein 4 (BRD4) bromodomain 1, BRD4 bromodomain 2, and bromodomain and PHD finger-containing 1 (BRPF1, IC50s = 5.1, 12, and 4.6 µM, respectively), as well as nine other bromodomain-containing proteins (IC50s = >18 µM for all). GNE-781 inhibits the expression of Myc in MV4-11 leukemia cells (EC50 = 6.6 nM). It reduces the differentiation of isolated human naïve CD4+ T cells into FOXP3+ inducible regulatory T cells (Tregs) in a concentration-dependent manner without affecting cell viability. Oral administration of GNE-781 (3-30 mg/kg) decreases tumor volume in a MOLM-16 acute myeloid leukemia (AML) mouse xenograft model.Formal Name: 3-[7-(difluoromethyl)-3,4-dihydro-6-(1-methyl-1H-pyrazol-4-yl)-1(2H)-quinolinyl]-1,4,6,7-tetrahydro-N-methyl-1-(tetrahydro-2H-pyran-4-yl)-5H-pyrazolo[4,3-c ]pyridine-5-carboxamide. CAS Number: 1936422-33-1. Molecular Formula: C27H33F2N7O2. Formula Weight: 525.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Soluble, DMSO: Soluble. SMILES: O=C(N1CC2=C(CC1)N(C3CCOCC3)N=C2N4C5=C(CCC4)C=C(C6=CN(C)N=C6)C(C(F)F)=C5)NC. InChi Code: InChI=1S/C27H33F2N7O2/c1-30-27(37)34-9-5-23-22(16-34)26(32-36(23)19-6-10-38-11-7-19)35-8-3-4-17-12-20(18-14-31-33(2)15-18)21(25(28)29)13-24(17)35/h12-15,19,25H,3-11,16H2,1-2H3,(H,30,37). InChi Key: CQCWHSDMJBAGDC-UHFFFAOYSA-N.