Cayman Dovitinib

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.

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