产品说明书
Neratinib
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同义名 : | 来那替尼 (HKI-272) ;HKI-272 |
| CAS号 : | 698387-09-6 | |
| 货号 : | A150970 | |
| 分子式 : | C30H29ClN6O3 | |
| 纯度 : | 98% | |
| 分子量 : | 557.043 | |
| MDL号 : | MFCD09752958 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 12 mg/mL(21.54 mM)，配合低频超声助溶，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 |
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| 动物实验配方： |
30% PEG400+0.5% Tween80+5% propylene glycol+water 5 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
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| 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. Neratinib is a potent inhibitor of HER2 and EGFR with IC50 values of 59nM and 92nM (measured by an autophosphorylation assay using time-resolved fluorometry), respectively. Neratinib>10nM could inhibit autophosphorylation of HER2 in BT474 cells treated for 3h, and EGF-induced autophosphorylation of EGFR in A431. Cell viability assays showed that Neratinib could inhibit HER-2-overexpressing breast cancer cell lines, SK-Br-3 and BT474, with low IC50 values (2nM), as well as EGFR-overexpressed cell line with IC50 value of 81nM, but exhibited much less activation on EGFR- and HER-2-negative cell lines, MDA-MB-435 and SW620. For activation of HER2 can lead to activation of both MAPK pathway and the Akt signal transduction pathways, a test for Neratinib on this two pathway has been done. Neratinib at concentration>2nM caused decreased level of both p-MAPK and p-AKT in BT474 cells. Treatment with Neratinib at concentration>5nM for 12-16h also led to decrease of cyclin D1 and retinoblastoma (Rb), as well as increased p27 in BT474, suggesting the cell cycle block by Neratinib. Oral administration of Neratinib at dose ranging in 10-80mg/kg exhibited anti-tumor activity against various tumor models, including 3T3/neu cells, BT474, SK-OV-3, A431 and MCF-7 xenografts[1]. | ||
| 作用机制 | Neratinib binds irreversibly to the ATP binding pocket of HER member receptor tyrosine kinases.[2] | ||
| 细胞研究 | |||||
|---|---|---|---|---|---|
| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| 3T3 | Growth Inhibition Assay | IC50=700 ± 78 nM | 15173008 | ||
| 3T3/neu | Growth Inhibition Assay | IC50=3 ± 0.14 nM | 15173008 | ||
| A431 | Growth Inhibition Assay | IC50=81 ± 9 nM | 15173008 | ||
| 临床研究 | |||||
|---|---|---|---|---|---|
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT02396108 | Breast Cancer | Phase 1 Phase 2 | Recruiting | March 2019 | Singapore ... 展开 >> National University Hospital Recruiting Singapore, Singapore, 119228 Contact: Soo Chin Lee (65) 6779 5555 收起 << |
| NCT03182634 | Advanced Breast Cancer | Phase 2 | Recruiting | November 2023 | United Kingdom ... 展开 >> Royal Marsden Hosital, Sutton Recruiting Surrey, England, United Kingdom, SM2 5PT Royal Bournemouth Hospital Recruiting Bournemouth, United Kingdom Addenbrooke's Hospital Recruiting Cambridge, United Kingdom Royal Devon and Exeter Hospital Recruiting Exeter, United Kingdom Beatson West of Scotland Cancer Centre Recruiting Glasgow, United Kingdom Royal Marsden Hospital Recruiting London, United Kingdom University College Hospital London Recruiting London, United Kingdom Christie Hospital Recruiting Manchester, United Kingdom 收起 << |
| NCT00366600 | Healthy | Phase 1 | Completed | - | United States, Washington ... 展开 >> Northwest Kinetics Tacoma, Washington, United States, 98418 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
1.80mL 0.36mL 0.18mL |
8.98mL 1.80mL 0.90mL |
17.95mL 3.59mL 1.80mL |
| 参考文献 |
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