Dovitinib-d8 is intended for use as an internal standard for the quantification of dovitinib by GC- or LC-MS. Dovitinib is a multi-kinase inhibitor. It inhibits the receptor tyrosine kinases FLT3, CSF1R, and c-Kit (IC50s = 1, 36, and 2 nM, respectively), as well as FGFR1, FGFR3, VEGFR1-3, PDFGRα, and PDGFRβ (IC50s = 8, 9, 10, 13, 8, 27, and 210 nM, respectively). Dovitinib inhibits proliferation of human multiple myeloma cell lines expressing mutant, but not wild-type, FGFR3 (IC50s = 90-550 and >2,500 nM, respectively). It decreases FGF-induced ERK1/2 phosphorylation and induces apoptosis in patient-derived multiple myeloma cells when used at a concentration of 500 nM. Dovitinib (3-300 mg/kg for eight days) inhibits bFGF-induced angiogenesis in a Matrigel™ plug assay in mice. It reduces tumor growth in KM12L4A colon, DU145 prostate, and MV4-11 acute myelogenous leukemia mouse xenograft models with ED50 values of 17, 23, and 3 mg/kg per day, respectively.
[1] SUZANNE TRUDEL. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma.[J]. Blood, 2005: 2941-2948. DOI:
10.1182/blood-2004-10-3913[2] PAUL A. RENHOWE*. Design, StructureActivity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors[J]. Journal of Medicinal Chemistry, 2008, 52 2: 278-292. DOI:
10.1021/jm800790t
