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Dovitinib(TKI-258,CHIR-258)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Dovitinib(TKI-258,CHIR-258)图片
CAS NO:405169-16-6
规格:98%
分子量:392.43
包装与价格:
包装价格(元)
5mg电议
25mg电议
100mg电议

产品介绍
Multitargeted RTK inhibitor
CAS:405169-16-6
分子式:C21H21FN6O
分子量:392.43
纯度:98%
存储:Store at -20°C

Background:

Dovitinib (TKI258, CHIR-258) is a multitargeted receptor tyrosine kinase inhibitor against FLT3, KIT, FGFR, VEGFR, PDGFRα and PDGFRβ with IC50 of 1 nM, 2 nM, 8-9 nM, 8-13 nM , 210 nM and 27nM, respectively [1].


The viability of ZNF198-FGFR1 or BCR-FGFR1 cells was specifically inhibited by TKI258 with IC50 values of 150 nM or 90 nM. The phosphorylation of ERK and STAT5 genes was inhibited by TKI258 in dose dependent manner. TKI258 also specifically inhibited proliferation and survival of the FGFR1OP2-FGFR1-positive KG1 and KG1A cell lines, increasing levels of apoptosis [2]. In hepatocellular carcinoma (HCC) cells, the combination of TKI258 and tigatuzumab restored the sensitivity of HCC cells to TRAIL- and tigatuzumab-induced apoptosis. TKI258 inhibited phosphorylation of STAT3 and subsequently reduced the protein levels of Mcl-1, Survivin and Cylcin D1. Co-treatment of TRAIL and TKI258 increased the activity of SHP-1 [3]. Inhibition of FGFR3 with TKI258 decreased waldenstr m macroglobulinemia (WM) cell survival, increased apoptosis, and induced cell cycle arrest. TKI258 reduced the interaction of WM to bone marrow element, and reversed its proliferation. TKI258 had an additive effect with other drugs [4].


In vivo, the combination of tigatuzumab and TKI258 inhibited Huh-7 xenograft tumor growth [3]. TKI258 reduced WM tumor progression [4].


Reference:
[1].? Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, Reece D, Heise C, Stewart AK. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood. 2005 Apr 1;105(7):2941-8.
[2].? Chase A, Grand FH, Cross NC. Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome. Blood. 2007 Nov 15;110(10):3729-34.
[3].? Chen KF, Chen HL, Liu CY, Tai WT, Ichikawa K, Chen PJ, Cheng AL. Dovitinib sensitizes hepatocellular carcinoma cells to TRAIL and tigatuzumab, a novel anti-DR5 antibody, through SHP-1-dependent inhibition of STAT3. Biochem Pharmacol. 2012 Mar 15;83(6):769-77.
[4].? Azab AK, Azab F, Quang P, Maiso P, Sacco A, Ngo HT, Liu Y, Zhang Y, Morgan BL, Roccaro AM, Ghobrial IM. FGFR3 is overexpressed waldenstrom macroglobulinemia and its inhibition by Dovitinib induces apoptosis and overcomes stroma-induced proliferation. Clin Cancer Res. 2011 Jul 1;17(13):4389-99.