Effects of dovitinib on cancers

     As we all know, cancers are always accompanied by pathological abnormality, such as growth, proliferation and migration of cancer cells. Many factors, as the biomarkers and targets, have been reported to be involved in the process, such as VEGF, PDGF, FGF, and their receptors as well as their downstream signaling components.

 

     Dovitinib (TKI258) is a highly potent and novel multitargeted inhibitor, which has been found to target for FLT3, c-KIT, FGFR, VEGFR1/2/3, PDGFRß and CSF-1R in vitro and in vivo. In some studies, dovitinib has also shown the potential antitumor activity via directly inhibiting FGFR and PDGFR, as well as antiangiogenic activity via inhibiting FGFR, VEGFR, and PDGFR[1]. At present, Dovitinib has been applied to clinical trials, and can be metabolized mainly by cytochrome  (CYP)1A1/2 and flavin-containing monooxygenase.
     In their recent paper, Kim and the colleagues carried out a prospective, phase I/II, dose–escalation study to evaluate effects of dovitinib on patients with advanced melanoma. The experiment showed that oral dovitinib has an acceptable safety profile and provides pharmacologic inhibition of both the VEGFR and FGFR, and the maximum tolerated dose was 400 mg/d. In addition, The most frequently reported adverse events were fatigue, diarrhea, and nausea[2].
     Taken together, dovitinib indeed has an acceptable safety clinically and inhibited FGFR and VEGFR at the maximum tolerated dose.

References
[1]. Clin Cancer Res 2005;11:3633–41.
[2]. Clin Cancer Res 2011; 17:1–11.

Related Products

Cat.No.	Product Name	Information
S1018	Dovitinib (TKI-258)	Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

Related Targets

VEGFR