VTP-50469

VTP-50469 is an inhibitor of the protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) fusion proteins (Ki = 0.104 nM). It selectively inhibits the growth of ten leukemia cell lines expressing MLL1 fusion proteins (IC50s = 13-37 nM) over HL-60 , K562, and Reh leukemia cells expressing wild-type MLL1 (IC50s = >1,000 nM). VTP-50469 reduces MLL-AF9-induced increases in the expression of MLL fusion protein target genes, including MEIS1, MEF2C, JMJD1C, and PBX3, in MOLM-13 acute myeloid leukemia (AML) cells. In vivo, VTP-50469 (120 mg/kg twice per day) dramatically increases the survival of mice in a patient-derived xenograft (PDX) mouse model of B cell acute lymphoblastic leukemia (B-ALL).Formal Name: 5-fluoro-N,N-bis(1-methylethyl)-2-[[4-[7-[[trans-4-[(methylsulfonyl)amino]cyclohexyl]methyl]-2,7-diazaspiro[3.5]non-2-yl]-5-pyrimidinyl]oxy]-benzamide. CAS Number: 2169916-18-9. Molecular Formula: C32H47FN6O4S. Formula Weight: 630.8. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble: >10 mg/ml, Ethanol: Sparingly soluble: 1-10 mg/ml. SMILES: CC(C)N(C(C)C)C(C(C=C(C=C1)F)=C1OC2=CN=CN=C2N(C3)CC43CCN(C[C@@H]5CC[C@H](CC5)NS(=O)(C)=O)CC4)=O. InChi Code: InChI=1S/C32H47FN6O4S/c1-22(2)39(23(3)4)31(40)27-16-25(33)8-11-28(27)43-29-17-34-21-35-30(29)38-19-32(20-38)12-14-37(15-13-32)18-24-6-9-26(10-7-24)36-44(5,41)42/h8,11,16-17,21-24,26,36H,6-7,9-10,12-15,18-20H2,1-5H3/t24-,26-. InChi Key: ADHHOUXZPBYYSU-YOCNBXQISA-N.