CHMFL-BMX-078

CHMFL-BMX-078 is an irreversible inhibitor of bone marrow tyrosine kinase on chromosome X (BMX, IC50 = 11 nM). It selectively inhibits the growth of Ba/F3 cells expressing BMX over Ba/F3 cells expressing Abl, c-Kit, PDGFRalpha, or PDGFRbeta (GI50s = 0.016, 2.56, 2.01, 0.67, and 0.91 µM, respectively), as well as Ba/F3 cells expressing FLT3, EGFR, JAK3, or Blk (GI50s = >10 µM for all). CHMFL-BMX-078 inhibits the growth of 22Rv1, DU145, and PC3 prostate, Hb-c, J82, and T24 bladder, and ACHN renal cancer cells (GI50s = 3.45-7.89, 5.78-8.98, and 4.93 µM, respectively). It restores cytotoxicity induced by vemurafenib (PLX4032, Cay-10618) in vemurafenib-resistant A375 melanoma cells. CHMFL-BMX-078 (15 mg/kg) reduces tumor weight and enhances vemurafenib-induced reduction of tumor weight in a vemurafenib-resistant A375 mouse xenograft model.Formal Name: 4-(methylamino)-2-[[4-methyl-3-[(1-oxo-2-propen-1-yl)amino]phenyl]amino]-N-[2-methyl-5-[(3,4,5-trimethoxybenzoyl)amino]phenyl]-5-pyrimidinecarboxamide. CAS Number: 1808288-51-8. Molecular Formula: C33H35N7O6. Formula Weight: 625.7. Purity: >90%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Slightly soluble. SMILES: O=C(NC1=CC(NC2=NC=C(C(NC)=N2)C(NC3=CC(NC(C4=CC(OC)=C(C(OC)=C4)OC)=O)=CC=C3C)=O)=CC=C1C)C=C. InChi Code: InChI=1S/C33H35N7O6/c1-8-28(41)38-24-16-22(12-10-18(24)2)37-33-35-17-23(30(34-4)40-33)32(43)39-25-15-21(11-9-19(25)3)36-31(42)20-13-26(44-5)29(46-7)27(14-20)45-6/h8-17H,1H2,2-7H3,(H,36,42)(H,38,41)(H,39,43)(H2,34,35,37,40). InChi Key: XURALSVDCFXBAX-UHFFFAOYSA-N.