产品说明书

TAK-285

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Chemical Structure| 871026-44-7 同义名 : -
CAS号 : 871026-44-7
货号 : A370749
分子式 : C26H25ClF3N5O3
纯度 : 99%+
分子量 : 547.957
MDL号 : MFCD22124520
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(91.25 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • EGFR/ErbB1

    EGFR/HER1, IC50:23 nM

  • HER2/ErbB2

    HER2, IC50:17 nM

  • ErbB4

    HER4, IC50:260 nM

  • HER2

    HER2, IC50:17 nM
描述 Deregulated expression of receptors EGFR and HER2, two closely related members of the ErbB family of transmembrane receptor tyrosine kinases, has been implicated in the development and malignancy of numerous types of human cancers, making them become a potential target for therapy. TAK-285 is a potent EGFR and HER2 inhibitor with IC50 values of 23nM and 17nM (measured by kinase assays), respectively[1], almost no activity against EGFR-T790M/L858R mutation[2]. Treatment with TAK-285 caused inhibition of HER2 phosphorylation in BT-474 cells with IC50 of 9.3nM, alone with inhibition of Akt and MAPK phosphorylation with IC50 of 15nM and <6.3nM, respectively. The inhibition of EGFR by TAK-285 can also be observed in A-431 cells with IC50 value of 53nM. Cell growth inhibition study showed that cell lines with higher expression of HER2, like BT-474 cells with IC50 of 17nM, as well as cells with overexpressed EGFR, like A-431 cells with 1.1μM, showed more sensitivity to TAK-285[3]. In vivo study showed the TAK-285 had good PK profiles and achieved much higher concentration levels in the tumor than plasma. Oral administration of TAK-285 at dose of 50mg/kg or 100mg/kg, twice daily, for 14 days exhibited dose-dependent tumor growth inhibition in BT-474 xenografts[1].
作用机制 TAK-285 interact with the the expected residues of ATP pocket.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.82mL

0.36mL

0.18mL

9.12mL

1.82mL

0.91mL

18.25mL

3.65mL

1.82mL
参考文献

[1]Ishikawa T, Seto M, et al. Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d] pyrimidine scaffold. J Med Chem. 2011 Dec 8;54(23):8030-50.

[2]Nakayama A, Takagi S, et al. Antitumor Activity of TAK-285, an Investigational, Non-Pgp Substrate HER2/EGFR Kinase Inhibitor, in Cultured Tumor Cells, Mouse and Rat Xenograft Tumors, and in an HER2-Positive Brain Metastasis Model. J Cancer. 2013 Aug 16;4(7):557-65.

[3]Sogabe S, Kawakita Y, et al. Structure-Based Approach for the Discovery of Pyrrolo[3,2-d] pyrimidine-Based EGFR T790M/L858R Mutant Inhibitors. ACS Med Chem Lett. 2012 Dec 18;4(2):201-5.