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Tivantinib

Tivantinib

产品编号 T6117   CAS 905854-02-6
别名: ARQ 197

Tivantinib (ARQ 197) 是一种高选择性c-Met 酪氨酸激酶抑制剂,Ki 为 355 nM。

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Tivantinib Chemical Structure
Tivantinib, CAS 905854-02-6
规格 价格/CNY 货期 数量
1 mg ¥ 198 现货
5 mg ¥ 462 现货
10 mg ¥ 693 现货
25 mg ¥ 1,290 现货
50 mg ¥ 2,320 现货
100 mg ¥ 3,160 现货
200 mg ¥ 4,630 现货
1 mL * 10 mM (in DMSO) ¥ 497 现货
产品目录号及名称: Tivantinib (T6117)
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纯度: 99.95%
纯度: 99.41%
纯度: 98%
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生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Tivantinib (ARQ 197) is an orally bioavailable small molecule inhibitor of c-Met with potential antineoplastic activity.
靶点活性 c-Met:0.355 μM(Ki)
体外活性 用ARQ-197处理的所有三种异种移植物模型显示肿瘤生长减少:HT29模型中66%,MKN-45模型中45%,MDA-MB-231模型中79%.口服给药200 mg/kg ARQ-197处理HT29,MKN-45和MDA-MB-231三种移植瘤模型,没有显著的体重变化.药效学方面,ARQ-197强效抑制人类结肠移植瘤HT29中c-Met的磷酸化,单独口服200 mg/kg ARQ-19724小时后,c-Met自磷酸化强烈下降.总之,ARQ-197抑制ARQ-197抑制c-Met依赖性异种移植人类肿瘤的生长.
体内活性 ARQ-197具有抗肿瘤活性,抑制A549,DBTRG和NCI-H441细胞增殖,IC50分别为0.38,0.45,0.29 μM。用ARQ-197处理,导致MAPK信号级联反应的磷酸化减少及预防侵入和迁移。此外,在没有内源性c-Met表达的细胞系NCI-H661中c-Met的异位表达导致其获得侵袭性表型,也被ARQ-197抑制。ARQ-197抑制人类重组c-Met,具有恒定的Ki值,为355 nM。ARQ-197抑制c-Met磷酸化,且阻断下游c-Met信号通路。尽管增加浓度的ARQ-197不会显著影响ATP的Km,但c-Met暴露于0.5 μMARQ-197会使c-Met的Vmax降低约3倍。ARQ-197降低Vmax而不影响ATP的Km值说明ARQ-197抑制c-Met是非ATP竞争抑制,也说明ARQ-197具有高度激酶选择性。ARQ-197抑制组成型和配体介导的c-Met自磷酸化,并且进而抑制c-Met活性,继而导致抑制下游c-Met效应物。在表达c-Met的人类癌细胞(包括HT29,MKN-45和MDA-MB-231细胞)中ARQ-197诱导胱天蛋白酶依赖性细胞凋亡增加。
激酶实验 c-Met SDS-PAGE in vitro kinase assay: Recombinant c-Met protein (100 ng) is preincubated with increasing concentrations of ARQ-197 for 30 minutes at room temperature. Following preincubation, 100 μM of poly-Glu-Tyr substrate and various concentrations of ATP containing 5 μCi of [γ-32P]ATP are added to the reaction mixture. The reaction is incubated for 5 minutes at room temperature and then stopped by the addition of 5 μL of SDS-polyacrylamide gel, reducing sample buffer. The samples are then loaded onto a 7.5% acrylamide gel and SDS-PAGE is performed. The phosphorylated poly-Glu-Tyr substrates are ultimately visualized by autoradiography. c-Met activity is quantified by densitometry.
细胞实验 HT29, MKN-45, and MDA-MB-231 cells are seeded in black 96-well plates at 5 × 103 cells per well overnight in a medium with 10% FBS. The next day, cells are treated with increasing concentrations of ARQ-197 (0.03-10 μM) for 24, 32, and 48 hours at 37 °C. After ARQ-197 treatment, the drug-containing medium is removed and cells are incubated for at least 10 minutes in a labeling solution (10 mM HEPES, 140 mM NaCl, and 6 mM CaCl2) containing 2 μg/mL Hoescht 33342 (blue channel), 500-times diluted Annexin V-FITC (green channel), and 1 μg/mL propidium iodide (red channel). High-content image acquisition and analysis are carried out. The program is set to take four images per well. The exposure time is set at 16.7 ms/10% gain, 500 ms/35% gain, and 300 ms/30% gain for the 4,6-diamidino-2-phenylindole, FITC, and rhodamine channels, respectively. Images are processed and the numbers of positive cells for each channel and each condition are determined. In addition, HT29 cells are treated with increasing concentrations of ARQ-197 for 32 hours in the absence or the presence of 25, 50, and 100 μM ZvAD-FMK (irreversible general caspase inhibitor), and the same procedures are undertaken. All experiments are done in triplicate. To determine whether the apoptotic effect is due to c-Met inhibition, the effect of ARQ-197 when glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and c-Met are knocked down using siRNA is investigated. HT29, MKN-45, and MDA-MB-231 cells are transfected with a nontargeted control siRNA, a gapgh-targeted control siRNA, or a met-targeted siRNA. After 3 days, c-Met, GAPDH, and β-actin expression levels are determined using specific antibodies. To determine if the effect is caspase dependent, HT29, MKN-45, and MDA-MB-231 cells are transfected with a met-targeted siRNA for 2 days and incubated in the absence or the presence of increasing concentrations of ZvAD-FMK for 1 additional day.A nontargeted siRNA and a gapgh-targeted siRNA (siRNA GAPDH) are also transfected in parallel, as controls. Cells are then stained with Annexin V-FITC and propidium iodide, and the percentage of apoptotic cells is determined.(Only for Reference)
别名 ARQ 197
分子量 369.42
分子式 C23H19N3O2
CAS No. 905854-02-6

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 68 mg/mL (184.1 mM)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

H2O: < 1 mg/mL (insoluble or slightly soluble)

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.7069 mL 13.5347 mL 27.0695 mL 67.6737 mL
5 mM 0.5414 mL 2.7069 mL 5.4139 mL 13.5347 mL
10 mM 0.2707 mL 1.3535 mL 2.7069 mL 6.7674 mL
20 mM 0.1353 mL 0.6767 mL 1.3535 mL 3.3837 mL
50 mM 0.0541 mL 0.2707 mL 0.5414 mL 1.3535 mL
100 mM 0.0271 mL 0.1353 mL 0.2707 mL 0.6767 mL

计算器

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稀释计算器
配液计算器
分子量计算器
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参考文献

1. Munshi N, et al. Mol Cancer Ther. 2010, 9(6), 1544-1553. 2. Comoglio PM, et al. Nat Rev Drug Discov, 2008, 7(6), 504-516.

文献引用

1. Huang Y, Guo Y, Zhou Y, et al.Tivantinib alleviates inflammatory diseases by directly targeting NLRP3.iScience.2023
Antitumor agent-111 Cabozantinib Davutamig Amuvatinib 1D228 MK-8033 c-Kit-IN-1 Caveolin-1 (82-101) amide (human, mouse, rat)

相关化合物库

该产品包含在如下化合物库中:
酪氨酸激酶分子库 抗癌药物库 抗癌活性化合物库 抗癌临床化合物库 高选择性抑制剂库 已知活性化合物库 临床期小分子药物库 药物功能重定位化合物库 激酶抑制剂库 抗肺癌化合物库

剂量换算

对于不同动物的给药剂量换算,您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。

体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
g
给药体积
μL
动物数量
第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
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技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

Tivantinib 905854-02-6 Apoptosis Tyrosine Kinase/Adaptors c-Met/HGFR inhibit ARQ 197 ARQ-197 ARQ197 Inhibitor inhibitor

 

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