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Crizotinib

产品编号 T1661 CAS 877399-52-5

别名: PF-02341066, 克唑替尼

Crizotinib (PF-02341066) 是 c-MET 和 ALK 受体的 ATP 竞争性小分子酪氨酸激酶抑制剂，IC50为 8和20 nM。在细胞的实验中，它抑制 NPM-ALK 的酪氨酸磷酸化和 c-Met 的酪氨酸磷酸化。它也是 ROS1抑制剂。它有肿瘤生长抑制作用。

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Crizotinib, CAS 877399-52-5

规格	价格/CNY	货期
5 mg	￥ 255	现货
10 mg	￥ 387	现货
50 mg	￥ 555	现货
100 mg	￥ 798	现货
200 mg	￥ 917	现货
500 mg	￥ 1,559	现货
1 mL * 10 mM (in DMSO)	￥ 391	现货

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其他形式的 Crizotinib:

选择批次

纯度: 99.87%

纯度: 99.35%

纯度: 99%

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生物活性

化学信息

存储 & 溶解度

参考文献

相关产品

产品描述	Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinases inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptor.
靶点活性	ALK:24 nM (cell free), c-Met:11 nM (A498 cells)
体外活性	Crizotinib (PF-2341066) potently inhibited c-Met phosphorylation and c-Met-dependent proliferation, migration, or invasion of human tumor cells in vitro (IC50: 5-20 nmol/L). In addition, PF-2341066 potently inhibited HGF-stimulated endothelial cell survival or invasion and serum-stimulated tubulogenesis in vitro [1]. Both of two cell lines with MET amplification, EBC-1, and H1993, were sensitive to crizotinib (IC50: 10 nM). In contrast, crizotinib did not substantially inhibit the proliferation of lung cancer cells with a MET mutation (H2122, H1437, and H596) [2]. PF-2341066 potently inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells (IC50: 24 nmol/L). PF-2341066 potently inhibited cell proliferation, which was associated with G(1)-S-phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells (IC50: 30 nmol/L) but not ALK-negative lymphoma cells. The induction of apoptosis was confirmed using terminal deoxyribonucleotide transferase-mediated nick-end labeling and Annexin V staining (IC50: 25-50 nmol/L) [3].
体内活性	PF-2341066 showed efficacy at well-tolerated doses, including marked cytoreductive antitumor activity, in several tumor models that expressed activated c-Met. The antitumor efficacy of PF-2341066 was dose-dependent and showed a strong correlation to the inhibition of c-Met phosphorylation in vivo. Near-maximal inhibition of c-Met activity for the full dosing interval was necessary to maximize the efficacy of PF-2341066. Additional mechanism-of-action studies showed a dose-dependent inhibition of c-Met-dependent signal transduction, tumor cell proliferation (Ki67), induction of apoptosis (caspase-3), and reduction of microvessel density (CD31) [1]. Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg crizotinib caused tumor regression that was associated with a slow reduction in (18)F-FDG uptake and reduced expression of the GLUT-1. Although baseline (18)F-FDG uptake into U87MG tumors was substantially higher than in GTL-16 tumors, (18)F-FDG uptake into U87MG tumors remained unchanged on treatment at 50 mg/kg crizotinib, despite tumor growth inhibition of 93% on day 8 of treatment [4].
激酶实验	c-Met catalytic activity was quantitated using a continuous-coupled spectrophotometric assay in which the time-dependent production of ADP by c-Met was determined by analysis of the rate of consumption of NADH. NADH consumption was measured by a decrease in absorbance at 340 nm by spectrophotometry at designated time points. To determine Ki values, PF-2341066 was introduced into test wells at various concentrations in the presence of assay reagents and incubated for 10 min at 37°C. The assay was initiated by the addition of the c-Met enzyme [1].
细胞实验	Cells were seeded in 96-well plates in media supplemented with 10% fetal bovine serum (FBS) and transferred to serum-free media (with 0.04% BSA) after 24 h. In experiments investigating ligand-dependent RTK phosphorylation, corresponding growth factors were added for up to 20 min. After incubation of cells with PF-2341066 for 1 h and/or appropriate ligands for the designated times, cells were washed once with HBSS supplemented with 1 mmol/L Na3VO4, and protein lysates were generated from cells. Subsequently, phosphorylation of selected protein kinases was assessed by a sandwich ELISA method using specific capture antibodies used to coat 96-well plates and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates were (a) incubated in the presence of protein lysates at 4°C overnight; (b) washed seven times in 1% Tween 20 in PBS; (c) incubated in a horseradish peroxidase-conjugated anti–total-phosphotyrosine (PY-20) antibody (1:500) for 30 min; (d) washed seven times again; (e) incubated in 3,3′,5,5′-tetramethylbenzidine peroxidase substrate to initiate a colorimetric reaction that was stopped by adding 0.09 N H2SO4; and (f) measured for absorbance in 450 nm using a spectrophotometer [1].
动物实验	Daily treatment with PF-2341066 given in water by oral gavage was initiated when tumors were 100 to 600 mm^3 in volume. Tumor volume was determined by measurement with electronic Vernier calipers, and tumor volume was calculated as the product of its length × width2 × 0.4. Tumor volume was expressed on indicated days as the median tumor volume ± SE indicated for groups of mice. Percent (%) inhibition values were measured on the final day of study for drug-treated compared with vehicle-treated mice and are calculated as 100 × {1?[(TreatedFinal day ? TreatedDay 1)/(ControlFinal day ? ControlDay 1)]}. Tumor regression values were determined by calculating the ratio of median tumor volumes at the time when treatment was initiated to the median tumor volume on the final day of study for a given treatment group. Significant differences between the treated versus the control groups (P ≤ 0.001) were determined using one-way ANOVA [1].

别名	PF-02341066, 克唑替尼
分子量	450.34
分子式	C21H22Cl2FN5O
CAS No.	877399-52-5

存储

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

溶解度

DMSO: 10 mg/mL (22.21 mM)

2eq.HCl: 45 mg/mL (100 mM)

溶液配制表

可选溶剂	浓度体积质量	1 mg	5 mg	10 mg	25 mg
DMSO / 2eq.HCl	1 mM	2.2205 mL	11.1027 mL	22.2054 mL	55.5136 mL
	5 mM	0.4441 mL	2.2205 mL	4.4411 mL	11.1027 mL
	10 mM	0.2221 mL	1.1103 mL	2.2205 mL	5.5514 mL
	20 mM	0.111 mL	0.5551 mL	1.1103 mL	2.7757 mL
2eq.HCl	50 mM	0.0444 mL	0.2221 mL	0.4441 mL	1.1103 mL
2eq.HCl	100 mM	0.0222 mL	0.111 mL	0.2221 mL	0.5551 mL

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参考文献

1. Zou HY, et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007, 67(9), 4408-4417. 2. Tanizaki J, et al. MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations.J Thorac Oncol. 2011 Oct;6(10):1624-31. 3. Christensen JG, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007, 6(12 Pt 1), 3314-3322. 4. Cullinane C, et al. Differential (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models. J Nucl Med. 2011 Aug;52(8):1261-7 6. Tucker ER, et al. Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma. Mol Oncol. 2017 Aug;11(8):996-1006. 7. Yang Y, Huang J, Xie N, et al. lincROR influences the stemness and crizotinib resistance in eMl–alK+ non-small-cell lung cancer cells[J]. OncoTargets and therapy. 2018 Jun 22;11:3649-3657. 8. Hu Y, Zhang X, Zhao Z, et al. Keratinocytes apoptosis contributes to crizotinib induced-erythroderma[J]. Toxicology Letters. 2019 9. Tao J, Tu Y, Liu P, et al. Detection of colorectal cancer using a small molecular fluorescent probe targeted against c-Met[J]. Talanta. 2021: 122128.

文献引用

1. Yan H, Wu W, Hu Y, et al.Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.Nature Communications.2023, 14(1): 2756. 2. Li P, Jia C, Fan Z, et al.Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations.Acta Pharmaceutica Sinica B.2023 3. Zou X, Zeng M, Zheng Y, et al.Comparative Study of Hydroxytyrosol Acetate and Hydroxytyrosol in Activating Phase II Enzymes.Antioxidants.2023, 12(10): 1834. 4. Jiao D, Chen Y, Liu X, et al.Targeting MET endocytosis or degradation to overcome HGF-induced gefitinib resistance in EGFR-sensitive mutant lung adenocarcinoma.Biochemical and Biophysical Research Communications.2023 5. Yu J, Zhang L, Peng J, et al. Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochemical pharmacology. 2022, 195: 114864. 6. Arechederra M, Bazai S K, Abdouni A, et al. ADAMTSL5 is an epigenetically activated gene underlying tumorigenesis and drug resistance in hepatocellular carcinoma. Journal of Hepatology. 2021, 74(4): 893-906. 7. Yang Y, Huang J, Xie N, et al. lincROR influences the stemness and crizotinib resistance in eMl–alK+ non-small-cell lung cancer cells. OncoTargets and Therapy. 2018 Jun 22;11:3649-3657 8. Tao J, Tu Y, Liu P, et al. Detection of colorectal cancer using a small molecular fluorescent probe targeted against c-Met. Talanta. 2021: 122128. 9. Hu Y, Zhang X, Zhao Z, et al. Keratinocytes apoptosis contributes to crizotinib induced-erythroderma. Toxicology Letters. 2019 10. Zheng Y D, Zhong T, Wu H, et al. Crizotinib Shows Antibacterial Activity against Gram-Positive Bacteria by Reducing ATP Production and Targeting the CTP Synthase PyrG. Microbiology Spectrum. 2022: e00884-22

11. Kastana P, Ntenekou D, Mourkogianni E, et al.Genetic deletion or tyrosine phosphatase inhibition of PTPRZ1 activates c‐Met to up‐regulate angiogenesis and lung adenocarcinoma growth.International Journal of Cancer..2023;1–16.

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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

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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。

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

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计算结果如下:

工作液浓度: mg/ml;

母液配置方法: mg 药物溶于 μL DMSO (母液浓度为 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 μL DMSO 主液，加入 μL PEG300，混匀澄清，再加 μL Tween 80，混匀澄清，再加 μL ddH₂O, 混匀澄清。

备注:

要按顺序从左向右依次添加助溶剂。可配合物理方法，如涡流、超声波或热水浴使之帮助溶解。

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

Crizotinib 877399-52-5 Angiogenesis Autophagy Immunology/Inflammation Tyrosine Kinase/Adaptors c-Met/HGFR ROS ALK ROS Kinase PF-02341066 Cluster of differentiation 246 克唑替尼 PF02341066 Inhibitor Anaplastic lymphoma kinase inhibit CD246 PF 02341066 ALK tyrosine kinase receptor Anaplastic lymphoma kinase (ALK) inhibitor

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Crizotinib

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