Powder: -20°C for 3 years | In solvent: -80°C for 1 year
PHA-665752 是一种选择性的 ATP 竞争活性位点 c-Met 激酶抑制剂,Ki 为 4 nM,IC50为 9 nM。它对 c-Met 的选择性比一组不同的酪氨酸和丝氨酸苏氨酸激酶高 50 倍。它诱导细胞凋亡和细胞周期阻滞,具有细胞还原性抗肿瘤活性。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 208 | 现货 | ||
5 mg | ¥ 478 | 现货 | ||
10 mg | ¥ 762 | 现货 | ||
25 mg | ¥ 1,580 | 现货 | ||
50 mg | ¥ 2,980 | 现货 | ||
100 mg | ¥ 4,590 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 785 | 现货 |
产品描述 | PHA-665752 is an effective, specific and ATP-competitive c-Met inhibitor (IC50: 9 nM), >50-fold selectivity for c-Met than STKs or RTKs. |
靶点活性 | c-Met:9 nM |
体外活性 | PHA-665752 significantly inhibits c-Met kinase activity with Ki of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. PHA-665752 potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. PHA-665752 also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 potently inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines. [1] PHA-665752 inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of <60 nM, and inhibits constitutive cell motility and migration by 92.5% at 0.2 μM. Inhibition of c-Met by PHA665752 (0.2 μM) also induces cell apoptosis of 33.1% and G1 cell cycle arrest with cells in G1 phase increasing from 42.4% to 77.0%. PHA665752 can cooperate with rapamycin to inhibit cell growth of TPR-MET-transformed BaF3 cells and non-small cell lung cancer H441 cells. [2] |
体内活性 | Administration of PHA-665752 induces a dose-dependent tumor growth inhibition of S114 xenografts by 20 %, 39% and 68%, at dose of 7.5, 15, and 30 mg/kg/day, respectively. [1] PHA665752 treatment significantly reduces the tumor growth of NCI-H69, NCI-H441 and A549 in mouse xenografts by 99%, 75%, and 59%, respectively. PHA665752 also significantly inhibits angiogenesis by >85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1. [3] |
激酶实验 | In vitro enzyme assay: The c-Met kinase domain GST-fusion protein is used for the c-Met assay. The IC50 value of PHA-665752 for the inhibition of c-Met is based on phosphorylation of kinase peptide substrates or poly-glu-tyr in the presence of ATP and divalent cation (MgCl2 or MnCl2 10-20 mM). The linear range (i.e., the time period over which the rate remains equivalent to the initial rate) is determined for c-Met, and the kinetic measurement and IC50 determination are performed within this range. |
细胞实验 | For proliferation assays, cells are grown in medium with 0.1% FBS for 48 hours after which they are treated with various concentrations of PHA-665752 in HGF (50 ng/mL) in a medium containing 2% FBS. After 18 hours, cells are incubated with BrdUrd for 1 hour, fixed, and stained with anti-BrdUrd peroxidase-conjugated antibody, and plates are read at 630 nm. For apoptosis assays, cells are grown in medium with 2% FBS in presence and absence of HGF (50 ng/mL) and various concentrations of PHA-665752 for 72 hours. After 72 hours, a mixture containing ethidium bromide and acridine orange is added, and apoptotic cells (bright orange cells or cell fragments) are counted by fluorescence microscopy.(Only for Reference) |
别名 | PHA 665752, PHA665752 |
分子量 | 641.61 |
分子式 | C32H34Cl2N4O4S |
CAS No. | 477575-56-7 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 64.2 mg/mL (100 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.5586 mL | 7.7929 mL | 15.5858 mL | 38.9645 mL |
5 mM | 0.3117 mL | 1.5586 mL | 3.1172 mL | 7.7929 mL | |
10 mM | 0.1559 mL | 0.7793 mL | 1.5586 mL | 3.8964 mL | |
20 mM | 0.0779 mL | 0.3896 mL | 0.7793 mL | 1.9482 mL | |
50 mM | 0.0312 mL | 0.1559 mL | 0.3117 mL | 0.7793 mL | |
100 mM | 0.0156 mL | 0.0779 mL | 0.1559 mL | 0.3896 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
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。
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。
PHA-665752 477575-56-7 Angiogenesis Apoptosis Autophagy Cytoskeletal Signaling Tyrosine Kinase/Adaptors VEGFR FGFR c-Met/HGFR Bcr-Abl Inhibitor inhibit PHA 665752 PHA665752 inhibitor