| 货号 | 规格 | 价格 | 上海 | 北京 | 珠海 | 重庆 | 武汉 | 购买数量 |
|---|---|---|---|---|---|---|---|---|
S81040-5mg买3赠1 |
99.00% | ￥1020.00 |
4 | - | - | - | - |
|
S81040-10mg买3赠1 |
99.00% | ￥1700.00 |
6 | - | - | - | - |
|
S81040-25mg买3赠1 |
99.00% | ￥3230.00 |
6 | - | - | - | - |
|
S81040-100mg |
≥99% | ￥7800.00 |
货期：2-3天 | - | - | - | - |
|
| 产品描述： | TAK-285 is a novel dual HER2 and EGFR(HER1) inhibitor with IC50 of 17 nM and 23 nM, >10-fold selectivity for HER1/2 than HER4, less potent to MEK1/5, c-Met, Aurora B, Lck, CSK etc. Phase 1. | ||||||||||||||||||||
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| 靶点： | MEK;HER;Aurora Kinase;EGFR;EGFR; MEK; HER; AuroraKinase | ||||||||||||||||||||
| 体外研究： | Among the 34 kinases tested, TAK-285 only significantly inhibits HER4 with IC50 of 260 nM,slightly inhibits MEK1, MEK5, c-Met, Aurora B, Lck, CSK, and Lyn B with IC50 of 1.1 μM,5.7 μM, 4.2 μM, 1.7 μM, 2.4 μM, 4.7 μM, and 5.2 μM, respectively, and displays noactivity against other kinases with IC50 of >10 μM. TAK-285 shows significant growth inhibitory activity against BT-474 cells (HER2-overexpressing human breast cancer cell line) with GI50 of 17 nM. Compared with SYR127063 a potent inhibitor of HER2, TAK-285 displays similar in vitro potency against HER2 and EGFR. Compared with the full cytoplasmic domains of the wild-type proteins, the mutations and shortened boundaries used for structure determination of HER2-KD and EGFR-KD do not significantly change the inhibitory activity (IC50) of TAK-285. TAK-285 binds to the inactive conformation of EGFR, and shows a similar binding mode with lapatinib in the active site. | ||||||||||||||||||||
| 体内研究： | The oral bioavailability of TAK-285 is 97.7% in rats and 72.2% in mice at a dose of 50 mg/kg. Oral administration of TAK-285 at 100 mg/kg twice daily for 14 days displays significant antitumor efficacy in the HER2-overexpressing BT-474 tumor xenograft mouse model with tumor/control (T/C) ratio of 29%, without affecting body weight. Similar to the BT-474 model, TAK-285 exhibits dose-dependent tumor growth inhibition of 4-1ST (HER2-overexpressing human gastric cancer tumor) xenografts in mice, with T/C of 44% and 11% at doses of 50 mg/kg and 100 mg/kg, twice daily, respectively, without significant body weight loss in mice. Furthermore, TAK-285 treatment induces dose-dependent growth inhibition of 4-1ST tumors in rats with T/C of 38% and 14% at doses of 6.25 mg/kg and 12.5 mg/kg, and, particularly noteworthy, tumor regression with T/C of -12% and -16% at doses of 25 mg/kg and 50 mg/kg, respectively. After oral administration of TAK-285, a significant amount of TAK-285 is present in the brain of rats in pharmacologically active, unbound form (approximately 20% of its free plasma level), indicating that TAK-285 has a potential in the therapy of CNS malignancies/metastases. | ||||||||||||||||||||
| 细胞实验： | The cells are treated continuously with various concentrations of TAK-285 for 5 days. The live cell numbers are counted with a particle analyzer.(Only for Reference) | ||||||||||||||||||||
| 参考文献： | 1. Aertgeerts K, et al. Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. J Biol Chem, 2011, 286(21), 18756-18765. 2. Ishikawa T, 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, 54(23), 8030-8050. 3. Erdo F, et al. Verification of brain penetration of the unbound fraction of a novel HER2/EGFR dual kinase inhibitor (TAK-285) by microdialysis in rats. Brain Res Bull, 2012, 87(4-5), 413-419. | ||||||||||||||||||||
| 溶解性： | Soluble in DMSO、Ethanol | ||||||||||||||||||||
| 保存条件： | -20℃ | ||||||||||||||||||||
| 配置溶液浓度参考： |
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| 注意： | 部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
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