Home>>Signaling Pathways>> Tyrosine Kinase>> PDGFR>>Dovitinib (TKI-258, CHIR-258)

Dovitinib (TKI-258, CHIR-258) Sale

(Synonyms: 多韦替尼; CHIR-258; TKI258) 目录号 : GC13547

A multi-kinase inhibitor

Dovitinib (TKI-258, CHIR-258) Chemical Structure

Cas No.:405169-16-6

规格 价格 库存 购买数量
5mg
¥357.00
现货
25mg
¥1,071.00
现货
100mg
¥2,751.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Kinase experiment [1]:

Inhibitory activities

IC50 values for the inhibition of RTKs by CHIR-258 were determined in a time-resolved fluorescence (TRF) or radioactive format, measuring the inhibition by CHIR-258 of phosphate transfer to a substrate by the respective enzyme. The kinase domains of FGFR3, FGFR1, PDGFR-β and VEGFR1-3 were assayed in 50 mM HEPES (N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid), pH 7.0, 2 mM MgCl2, 10 mM MnCl2, 1 mM NaF, 1 mM dithiothreitol (DTT), 1 mg/mL bovine serum albumin (BSA), 0.25 μM biotinylated peptide substrate (GGGGQDGKDYIVLPI), and 1 to 30 μM adenosine triphosphate (ATP) depending on the Km for the respective enzyme. ATP concentrations were at or just below Km. For c-KIT and FLT3 reactions the pH was raised to 7.5 with 0.2 to 8 μM ATP in the presence of 0.25 to 1 μM biotinylated peptide substrate (GGLFDDPSYVNVQNL). Reactions were incubated at room temperature for 1 to 4 hours and the phosphorylated peptide captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA, 50mM HEPES, pH 7.5).

Cell experiment [1]:

Cell lines

Human multiple myeloma (MM) cell lines and B9 cells

Preparation method

The solubility of this compound in DMSO is >36.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

100 nM CHIR-258; 48-96 h.

Applications

Dovitinib is a receptor tyrosine kinases inhibitor. Dovitinib selectively inhibits the growth of human myeloma cell lines and B9 cells expressing wild-type (WT) or activated mutant FGFR3. Dovitinib also causes cytostatic and cytotoxic effects and inhibits downstream extracellular signal-regulated kinase (ERK) 1/2 phosphorylation.

Animal experiment [1]:

Animal models

6- to 8-week-old female BNX mice bearing 3 ×107 KMS11 cells.

Dosage form

10, 30, or 60 mg/kg for 21 days by gavage.

Preparation method

Dissolved in dimethyl sulfoxide (DMSO) at a stock concentration of 20 mM. For animal experiments: formulated in 5 mM citrate buffer.

Applications

Dovitinib causes antitumor effect and inhibits tumor growths by 48%, 78.5%, and 94% in the 10 mg/kg, 30 mg/kg, and 60 mg/kg treatment arms, respectively. Weight loss, as a marker of significant toxicity, is not observed in any of the treatment groups. Dovitinib completely inhibits FGFR3 at the 60 mg/kg dose. CHIR-258 induces both cytostatic and cytotoxic responses.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Trudel S, Li ZH, Wei E, et al. CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood, 2005, 105(7): 2941-2948.

产品描述

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.

Chemical Properties

Cas No. 405169-16-6 SDF
别名 多韦替尼; CHIR-258; TKI258
化学名 (3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazin-1-yl)-1,3-dihydrobenzimidazol-2-ylidene]quinolin-2-one
Canonical SMILES CN1CCN(CC1)C2=CC3=C(C=C2)NC(=C4C(=C5C(=NC4=O)C=CC=C5F)N)N3
分子式 C21H21FN6O 分子量 392.43
溶解度 ≥ 36.35mg/mL in DMSO 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.5482 mL 12.7411 mL 25.4823 mL
5 mM 0.5096 mL 2.5482 mL 5.0965 mL
10 mM 0.2548 mL 1.2741 mL 2.5482 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置