TAK-285
目录号 : GC11172
A dual inhibitor of EGFR and HER2
Cas No.:871026-44-7
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
The BT-474 human breast cancer cell line, MES-SA human uterine sarcoma cells and multidrug-resistant MES-SA/DX-5 cells |
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Preparation method |
The solubility of this compound in DMSO is >27.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.00097-25 μmol/L, 3-7 days |
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Applications |
In BT-474 cells, TAK-285 inhibited cell growth with IC50 value of 0.017 μmol/L, compared with the IC50 values of 1.1 and 20 μmol/L in A-431 and MRC-5 cells which did not overexpress HER2. TAK-285 inhibited HER2, Akt and MAPK phosphorylation with IC50 values of 0.0093 μmol/L, 0.015 μmol/L and <0.0063 μmol/L, respectively. In A-431 cells, TAK-285 inhibited EGFR phosphorylation with IC50 value of 0.053 μmol/L. |
| Animal experiment [1]: | |
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Animal models |
Female BALB/c nu/nu mice implanted subcutaneously with BT-474 cells or 4-1ST tumors; female F344/N athymic (rnu/rnu) rats implanted with A-431 cells or 4-1ST tumors |
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Dosage form |
100 mg/kg BID or 12.5 mg/kg BID, emulsified in 0.5% methyl cellulose, administered orally, 2 weeks |
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Application |
In murine xenograft models, TAK-285 (100 mg/kg BID) inhibited BT-474 breast tumors and 4-1ST gastric tumor growth with T/C values of 29% and 11%, respectively. In rat xenografts, TAK-285 (12.5 mg/kg BID) inhibited growth of tumors that overexpressed HER2 (4-1ST) or EGFR (A-431) with T/C values of 14% and 13%, respectively. The pharmacokinetic profile for TAK-285 showed much greater drug exposure in rats compared with mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 871026-44-7 | SDF | |
| 化学名 | N-[2-[4-[3-chloro-4-[3-(trifluoromethyl)phenoxy]anilino]pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-3-hydroxy-3-methylbutanamide | ||
| Canonical SMILES | CC(C)(CC(=O)NCCN1C=CC2=C1C(=NC=N2)NC3=CC(=C(C=C3)OC4=CC=CC(=C4)C(F)(F)F)Cl)O | ||
| 分子式 | C26H25ClF3N5O3 | 分子量 | 547.96 |
| 溶解度 | ≥ 27.4mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.825 mL | 9.1248 mL | 18.2495 mL |
| 5 mM | 0.365 mL | 1.825 mL | 3.6499 mL |
| 10 mM | 0.1825 mL | 0.9125 mL | 1.825 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet