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TAK-285

现货
Catalog No.
A8528
HER2/EGFR(HER1)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,650.00
Ship with 10-15 days
5mg
¥ 1,890.00
Ship with 10-15 days
10mg
¥ 3,290.00
Ship with 10-15 days

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Background

TAK-285 is a potent inhibitor of HER2 and EGFR with IC50 value of 17 nM and 23 nM, respectively [1].

EGFR (epidermal growth factor receptor) and HER2 are members of ErbB family of receptors and play an important role in stimulating its intrinsic intracellular protein-tyrosine kinase activity. It has been shown that the over-expressions of HER-2 and EGFR are correlated with a variety of cancers and thus be regarded as promising target in clinic [2].

TAK-285 is a selective HER2 and EGFR inhibitor and has a different selectivity with the reported HER inhibitor AST-6. When tested with a panel of breast cancer cell lines, cells over-expressed HER2 (BT-474, NCI-N87, SK-BR-3, Calu-3, and MDA-MB-453) or EGFR (A-431) were more sensitive to TAK-285 treatment while normal expressed cell line (MRC-5) was less sensitive [1]. [3].

In rat model with 4-1ST (over-express HER2) or A-431 (over-express EGFR) subcutaneous xenograft, administration of TAK-285 caused significant reduction of tumor growth with T/C values of 14% and 13%, respectively, at a dose of 12.5 mg/kg, compared with control group [1]. In a panel of human breast cancer cell lines expressing EGFR, HER2, HER3, and HER4, administration of TAK-285 significantly inhibited cell proliferation in a dose-dependent manner with IC50 values range from 0.011 to 17 μM [3].

It is also reported that TAK-285 inhibited Akt and MAPK phosphorylation with IC50 value of 0.015 μM and <0.0063 μM, respectively [1].

References:
[1].  Nakayama, A., 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. 4(7): p. 557-65.
[2].  Lyakhov, I., et al., HER2- and EGFR-specific affiprobes: novel recombinant optical probes for cell imaging. Chembiochem, 2010. 11(3): p. 345-50.
[3].   Takagi, S., et al., HER2 and HER3 cooperatively regulate cancer cell growth and determine sensitivity to the novel investigational EGFR/HER2 kinase inhibitor TAK-285. Oncoscience, 2014. 1(3): p. 196-204.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt547.96
Cas No.871026-44-7
FormulaC26H25ClF3N5O3
Solubility≥27.4mg/mL in DMSO
Chemical NameN-[2-[4-[3-chloro-4-[3-(trifluoromethyl)phenoxy]anilino]pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-3-hydroxy-3-methylbutanamide
SDFDownload SDF
Canonical SMILESCC(C)(CC(=O)NCCN1C=CC2=C1C(=NC=N2)NC3=CC(=C(C=C3)OC4=CC=CC(=C4)C(F)(F)F)Cl)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[1]:

细胞系

BT-474人乳腺癌细胞系,MES-SA人子宫肉瘤细胞和多药耐药MES-SA / DX-5细胞

溶解方法

该化合物在DMSO中的溶解度>27.4mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0.00097-25 μmol/L, 3-7天

应用

在BT-474细胞中,与未过表达HER2的A-431和MRC-5细胞(IC50值为1.1和20μmol/ L)相比,TAK-285抑制细胞生长,IC50值为0.017μmol/ L。TAK-285抑制HER2,Akt和MAPK磷酸化,IC50值分别为0.0093μmol/ L,0.015μmol/ L和<0.0063μmol/ L。在A-431细胞中,TAK-285抑制EGFR磷酸化,IC50值为0.053μmol/ L。

动物实验[1]:

动物模型

皮下植入BT-474细胞或4-1ST肿瘤的雌性BALB/c nu/nu小鼠; 植入A-431细胞或4-1ST肿瘤的雌性F344/N无胸腺(rnu / rnu)大鼠

剂量

100 mg/kg BID或12.5 mg/kg BID, 在0.5%甲基纤维素中乳化,口服给药2周

应用

在鼠异种移植模型中,TAK-285(100mg / kg BID)抑制BT-474乳腺肿瘤和4-1ST胃肿瘤生长,T/C值分别为29%和11%。在大鼠异种移植物中,TAK-285(12.5mg / kg BID)抑制过表达HER2(4-1ST)或EGFR(A-431)的肿瘤生长,T/C值分别为14%和13%。与小鼠相比,TAK-285的药物动力学特征显示在大鼠中较大的药物暴露量。

注意事项

请测试所有化合物在室内的溶解度,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:

[1]. Nakayama, A., 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. 4(7): p. 557-65.

生物活性

Description TAK-285是HER2和EGFR(HER1)的新型双重抑制剂,其IC50值分别为17 nM和23 nM。
靶点 HER2 EGFR/HER1 HER4 MEK1 Aurora B  
IC50 17 nM 23 nM 260 nM 1.1 μM 1.7 μM  

质量控制

质量控制和MSDS

批次:

化学结构

TAK-285