Dovitinib (lactate)

692737-80-7

C24H27FN6O4

DMSO : >= 30 mg/mL (62.17 mM)

Protein Tyrosine Kinase/RTK

Dovitinib(CHIR-258; TKI258) lactate is a potent inhibitor of fibroblast growth factor receptor 3 (FGFR3) with an IC₅₀ of 5 nM. IC50 & Target: IC50: 5 nM (FGFR3)^[1] In Vitro: Dovitinib potently inhibits FGFR3 with an IC₅₀ of 5 nM in in vitro kinase assays and selectively inhibits the growth of B9 cells and human myeloma cell lines expressing wild-type or activated mutant FGFR3. Addition of interleukin 6 (IL-6) or insulin growth factor 1 or coculture on stroma does not confer resistance to dovitinib. In primary myeloma cells dovitinib inhibits downstream extracellular signal-regulated kinase (ERK) 1/2 phosphorylation with an associated cytotoxic response^[1]. Treatment of SK-HEP1 cells with dovitinib results in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibits basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-alpha and ERK1/2^[2]. In Vivo: Dovitinib demonstrates significant antitumor and antimetastatic activities in HCC xenograft models. Dovitinib potently inhibits tumor growth of six HCC lines. Inhibition of angiogenesis correlates with inactivation of FGFR/PDGFR-beta/VEGFR-2 signaling pathways. Dovitinib also causes dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which results in a reduction in cellular proliferation and the induction of tumor cell apoptosis^[2].