Dovitinib (CHIR-258) is an orally active and potent receptor tyrosine kinase (RTK) inhibitor against class III (FLT3/KIT/PDGFR1/CSFR/PDGFR2 IC50 = 1/2/27/36/200 nM), class IV (FGFR1/3 IC50 = 8/9 nM), and class V (VEGFR1/2/3 IC50 = 10/13/8 nM) RTKs, but not INSR, EGFR1, ErbB2 or Raf (IC50 = 2.1, 2.2, >20, >25 μM, respectively). Dovitinib inhibits target RTKs phosphorylation in cultured cells (pVEGFR1 and pPDGFRβ IC90 <50 nM; KM12L4a) and exhibits in vivo anti-tumor efficacy in mice bearing KM12L4a or HCT116 human cancer xenografts (10-120 mg/kg/day p.o.).
Orally active, potent inhibitor against class III-V receptor tyrosine kinases (FLT3, KIT, PDGFR1/2, CSFR, FGFR1/3, VEGFR1/2/3) with efficacy in vitro and in vivo.
Anti-cancer agents in medicinal chemistry, 20(6), 751-755 (2020-02-14)
Identification of the antitumor role of tyrosine kinase inhibitors, such as TKI-258, may lead to novel therapeutics for Oral Squamous Cell Carcinoma (OSCC), which has high mortality rates. TKI-258 blocks Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs)
To compare the inhibitory effects of dovitinib and bevacizumab for treatment of corneal neovascularization (CNV). Thirty-nine adult female Sprague Dawley rats weighing 180 to 250 g were used. CNV was induced by silver nitrate in the right eye of each
The 8p11 myeloproliferative syndrome (EMS) is an aggressive, atypical stem cell myeloproliferative disorder associated with chromosome translocations that disrupt and constitutively activate FGFR1 by fusion to diverse partner genes. To explore the possibility of targeted therapy for EMS, we have
Dovitinib (TKI258/CHIR258) is a multi-kinase inhibitor in phase III development for the treatment of several cancers. Dovitinib is a benzimidazole-quinolinone compound that structurally resembles the bisbenzimidazole minor groove binding dye Hoechst 33258. Dovitinib bound to DNA as shown by its
Clinical cancer research : an official journal of the American Association for Cancer Research, 11(14), 5281-5291 (2005-07-22)
Fms-like tyrosine kinase 3 (FLT3) encodes a receptor tyrosine kinase (RTK) for which activating mutations have been identified in a proportion of acute myelogenous leukemia (AML) patients and associated with poor clinical prognosis. Given the relevance of FLT3 mutations in
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