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Dovitinib

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Chemical Structure| 405169-16-6 同义名 : 度维替尼 ;CHIR-258;TKI258
CAS号 : 405169-16-6
货号 : A325412
分子式 : C21H21FN6O
纯度 : 99%+
分子量 : 392.43
MDL号 : MFCD10565680
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(63.71 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • VEGFR1

    VEGFR1/FLT1, IC50:10 nM

  • VEGFR3

    VEGFR3/FLT4, IC50:8 nM

  • VEGFR2

    VEGFR2/Flk1, IC50:13 nM

  • PDGFRβ

    PDGFRβ, IC50:27 nM
描述 Receptor tyrosine kinases (RTK) are mediators of cellular proliferation. These transmembrane RTKs contain an extracellular domain for ligand binding and intracellular kinase domains that mediate autophosphorylation, recruitment of downstream signaling molecules, and signal transduction. Type III RTKs, such as PDGFR (platelet-derived growth factor receptor), FGFR (fibroblast growth factor receptor), VEGFR (vascular endothelial growth factor receptor), FLT3 and c-KIT are often overexpressed in tumor and implicated in tumor growth and progression[3]. Tandutinib is an inhibitor of FLT3, PDGFR and c-Kit. The kinase inhibitory IC50s were 0.22, 0.20 and 0.17 μM, respectively. Tandutinib inhibited phosphorylation of WT FLT3 and FLT3-ITD (internal tandem duplication) in Ba/F3 cells with IC50s of 30-100nM. Tandutinib inhibited cell proliferation of the FLT3-ITD-positive cells (Molm-13 and Molm-14 cells） with an IC50 value of 10 nM, whereas the FLT3-ITD-negative cells (THP-1, KG-1, and RS4 cells) were resistant, requiring 1000-fold higher concentrations to inhibit cell growth. Treatment of Molm-14 cells with 1 μM tandutinib resulted in an increase of the percentage of apoptotic cells from a background level of 5% to 51% at 24h and 78% at 96h[6]. Tandutinib preferentially inhibited the growth of blast colonies derived from FLT3 ITD-positive patients with IC50s between 75 and 400 nM[7]. In a nude mice model established by injection of FLT3-ITD-transformed Ba/F3 cells, oral administration of tandutinib at 60 mg/kg bid significantly increased the survival of mice and resulted in a significant reduction in mortality in a mouse bone marrow transplantation model[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
5637 1-10 μM Cell Viability Assay 72 h inhibits cell growth in a dose dependent manner 24325461
8226 Growth Inhibition Assay 72 h IC50> 2500 nM 15598814
97-7 Growth Inhibition Assay 5 d IC50=1000 nM 21119661
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.55mL

0.51mL

0.25mL

12.74mL

2.55mL

1.27mL

25.48mL

5.10mL

2.55mL
参考文献

[1]Huynh H, Chow PK, et al. Dovitinib demonstrates antitumor and antimetastatic activities in xenograft models of hepatocellular carcinoma. J Hepatol. 2012 Mar;56(3):595-601.

[2]Huynh H, Chow PK, et al. Dovitinib demonstrates antitumor and antimetastatic activities in xenograft models of hepatocellular carcinoma. J Hepatol. 2012 Mar;56(3):595-601.

[3]Lee SH, Lopes de Menezes D, Vora J, Harris A, Ye H, Nordahl L, Garrett E, Samara E, Aukerman SL, Gelb AB, Heise C. In vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon cancer models. Clin Cancer Res. 2005 May 15;11(10):3633-41. doi: 10.1158/1078-0432.CCR-04-2129. PMID: 15897558.

[4]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.

[5]Eucker J, Zang C, Zhou Y, Li X, Habbel P, Schulz CO, Scholz C, Liu H. TKI258, a multi-tyrosine kinase inhibitor is efficacious against human infant/childhood lymphoblastic leukemia in vitro. Anticancer Res. 2014 Sep;34(9):4899-907.

[6]Kelly LM, Yu JC, Boulton CL, Apatira M, Li J, Sullivan CM, Williams I, Amaral SM, Curley DP, Duclos N, Neuberg D, Scarborough RM, Pandey A, Hollenbach S, Abe K, Lokker NA, Gilliland DG, Giese NA. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell. 2002 Jun;1(5):421-32. doi: 10.1016/s1535-6108(02)00070-3. PMID: 12124172.

[7]Griswold IJ, Shen LJ, La Rosée P, Demehri S, Heinrich MC, Braziel RM, McGreevey L, Haley AD, Giese N, Druker BJ, Deininger MW. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood. 2004 Nov 1;104(9):2912-8. doi: 10.1182/blood-2003-05-1669. Epub 2004 Jul 8. PMID: 15242881.