切换导航

TAK-733

现货
Catalog No.
B1621
MEK变构位点抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,250.00
现货
5mg
¥ 1,200.00
现货
10mg
¥ 2,250.00
现货
50mg
¥ 6,800.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

TAK-733 is a potent, ATP-noncompetitive and selective inhibitor of MEK allosteric site with the IC50 value of 3.2nM [1].

TAK-733 has been shown potent enzymatic and cell activity with an IC50 value of 3.2nM against constitutively active MEK enzyme and an EC50 of 1.9nM against ERK phosphorylation in cells. In addition, TAK-733 has also shown the low clearance and high oral bioavailability based on the pharmacokinetics of TAK-733 in all species (Mouse, rat, dog and Monkey). Furthermore, TAK-733 has been reported to broad inhibit tumor activity in mouse xenograft models of human cancer (melanoma, colorectal, NSCLC, pancreatic and breast cancer) [1].

References:
[1] Dong Q1, Dougan DR, Gong X, Halkowycz P, Jin B, Kanouni T, O'Connell SM, Scorah N, Shi L, Wallace MB, Zhou F. Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9. doi: 10.1016/j.bmcl.2011.01.071. Epub 2011 Jan 22.

文献引用

1. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt504.23
Cas No.1035555-63-5
FormulaC17H15F2IN4O4
Solubility≥25.2mg/mL in DMSO
Chemical Name3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione
SDFDownload SDF
Canonical SMILESCN1C2=C(C(=C(C1=O)F)NC3=C(C=C(C=C3)I)F)C(=O)N(C=N2)CC(CO)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验:

细胞系

人皮肤黑素瘤细胞系; 结肠直肠癌(CRC)细胞系

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

0.01-0.125 μM;72 h

应用

TAK-733在大多数黑素瘤细胞系中显示出广泛的活性,表现出相对耐药抗性,体外IC50 > 0.1 μmol/L [1]。 此外,具有BRAF或KRAS突变的细胞系对TAK-733药物更加敏感,其IC50值< 0.5 μM [2]。

动物实验:

动物模型

A375人黑色素瘤细胞异种移植小鼠模型;患者来源的结肠直肠癌(CRC)细胞异种移植模型

剂量

1、3、10或35 mg/kg、口服灌胃、每日一次、共2周; 或10 mg / kg、口服灌胃、每日一次、持续28天。

应用

TAK-733在患者衍生肿瘤细胞异种移植模型中显示出统计学显著肿瘤生长抑制效果 [1]。此外,TAK-733诱导患者来源的结肠直肠癌(CRC)细胞异种移植模型的肿瘤生长抑制并且抑制MEK途径 [2]。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1Micel, L. N., Tentler, J. J., Tan, A. C., Selby, H. M., Brunkow, K. L., Robertson, K. M., Davis, S. L., Klauck, P. J., Pitts, T. M., Gangolli, E., Fabrey, R., O'Connell, S. M., Vincent, P. W. and Eckhardt, S. G. (2015) Antitumor activity of the MEK inhibitor TAK-733 against melanoma cell lines and patient-derived tumor explants. Mol Cancer Ther. 14, 317-325

2Lieu, C. H., Klauck, P. J., Henthorn, P. K., Tentler, J. J., Tan, A. C., Spreafico, A., Selby, H. M., Britt, B. C., Bagby, S. M., Arcaroli, J. J., Messersmith, W. A., Pitts, T. M. and Eckhardt, S. G. (2015) Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts. Oncotarget. 6, 34561-34572

生物活性

Description TAK-733是一种有效的MEK变构位点选择性抑制剂,对MEK1的IC50值为3.2 nM.
靶点 MEK1          
IC50 3.2 nM          

质量控制