Dovitinib, Lactate Salt **
產品名稱：Dovitinib, Lactate Salt
產品貨號：LC D-3699
產品規(guī)格：100 MG
Dovitinib is a small-molecule multitargeted receptor tyrosine kinase inhibitor.
Dovitinib inhibited proliferation of ZNF198-FGFR1 and BCR-FGFR1 transformed Ba/F3 cells with IC50 values of 150 nM and 90 nM, respectively. The phosphorylation of each fusion gene, ERK, and STAT5 was inhibited as well at the same time. Dovitinib also inhibited proliferation of the FGFR1OP2-FGFR1-positive KG1 and KG1A cell lines and induced apoptosis. Furthermore, dovitinib significantly inhibited the growth of primary cells from 8p11 myeloproliferative syndrome (EMS) patients dose-dependently. Chase, A., et al. "Activity of TKI258 against primary cells and cell lines with FGFR1-fusion genes associated with the 8p11 myeloproliferative syndrome." Blood 110: 3729-3734 (2007).
Dovitinib potently inhibits receptor tyrosine kinases including FLT3, c-KIT, CSF-1R/c-fms, FGFR1, FGFR3, VEGFR1/Flt1,VEGFR2/Flk1, VEGFR3/Flt4, PDGFRβ, and PDGFRα with IC50 values of 1, 2, 36, 8, 9, 10, 13, 8, 27, and 210 nM, respectively. Dovitinib selectively blocked the growth of wild-type (WT) or activated mutant FGFR3-transformed B9 cells and human myeloma cell lines. Dovitinib was an effective treatment in a xenograft mouse model of FGFR3 multiple myeloma (MM). Trudel, S., et al. "CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma." Blood 105: 2941-2948 (2005).
Dovitinib treatment showed antitumor and antiangiogenic activities in xenograft models of human colon cancer. Dovitinib inhibited vascular endothelial growth factor receptor 1/2, fibroblast growth factor receptor 1/3, platelet-derived growth factor receptor β (PDGFR-β), the phosphorylation of PDGFR-β and extracellular signal-regulated kinase (ERK) in tumors. Lee, S.H., et al. "In vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon cancer models." Clin. Cancer Res. 11: 3633-3641 (2005).
Dovitinib was examined on two human leukemic cell lines with differing FLT3 mutational status in vitro and in vivo, including MV4;11 cells expressing FLT3 internal tandem duplications (ITD) and RS4;11 cells with wild-type (WT) FLT3. Antiproliferative activity of dovitinib against MV4;11 was about 24-fold greater than against RS4;11. Lopes de Menezes, D.E., et al. "CHIR-258: a potent inhibitor of FLT3 kinase in experimental tumor xenograft models of human acute myelogenous leukemia." Clin. Cancer Res. 11: 5281-5291 (2005).
Dovitinib significantly inhibited KMS-11-luc tumor growth and improved animal survival at doses that inhibited FGFR3 signaling in KMS-11-luc tumors in vivo. Xin, X., et al. "CHIR-258 is efficacious in a newly developed fibroblast growth factor receptor 3-expressing orthotopic multiple myeloma model in mice." Clin. Cancer Res. 12: 4908-4915 (2006).
This dovitinib product is the lactate salt, whose CAS number is given above. We also offer the free base -- please see Cat. No. D-3608, Dovitinib, Free Base. The CAS number of dovitinib free base is 405169-16-6.
Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL; very poorly soluble in ethanol; soluble in water at 200 mg/mL; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A
