产品说明书
Mubritinib
 |
同义名 : | TAK-165 |
| CAS号 : | 366017-09-6 | |
| 货号 : | A137400 | |
| 分子式 : | C25H23F3N4O2 | |
| 纯度 : | 99%+ | |
| 分子量 : | 468.471 | |
| MDL号 : | MFCD09954135 | |
| 存储条件： |
粉末 Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 50 mg/mL(106.73 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： |
IP 2% DMSO+2% Tween80+40% PEG300+water 2 mg/mL clear PO 0.5% CMC-Na 18 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
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| 描述 | Human epidermal growth factor receptor (EGFR; HER1,erbB1), human epidermal growth factor r eceptor 2 (HER2; erbB2), HER3 (erbB3) and HER4 (erbB4) are members of the ErbB family of transmembrane receptor tyrosine kinases. Among them, HER2 is a validated and high-value target. Overexpression of HER2 occurs in gastric, colorectal, NSCLC, breast and ovarian cancers. Mubritinib is a highly selective Her2 inhibitor with IC50 value of 6nM (measured by tyrosine-kinase activity), with almost no inhibition of other related target including EGFR, FGFR, PDGFR, Jak1, Src and Blk (all IC50 values>25000nM). Treatment with mubritinib at concentration>0.1μM for 2h caused significant decrease of autophosphorylation of Her2, as well as phosphorylation level of the key signal transduction mediator AKT and MAPK, in BT474 cells overexpressing HER2. The sensitivity of cell to Mubritinib depended on HER2 levels, as BT474 cells over-expressing HER2 strongly with highly sensitivity to Mubritinib (IC50=0.005µM), PC-3 cells expressing HER2 very weakly with less sensitive to Mubritinib (IC50=4.62µM), and HT1376 and ACHN cells over-expressed EGFR with much higher IC50 values (>25μM). Oral administration of 20mg/kg Mubritinib twice daily for 2 weeks significantly inhibited tumor growth in UMUC-3 bladder cancer model, as well as LN-REC4 prostate cancer model at dose of 10 or 20mg/kg[1]. | ||
| 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 |
| NCT00034281 | Breast Neoplasm ... 展开 >> Pancreatic Neoplasm Lung Neoplasm Ovarian Neoplasm Renal Neoplasm 收起 << | Phase 1 | Completed | - | United States, Arizona ... 展开 >> Arizona Cancer Center Scottsdale, Arizona, United States, 85258 United States, Texas The Institute for Drug Development San Antonio, Texas, United States, 78229 Brooke Army Medical Center/Drug Development Unit San Antonio, Texas, United States, 78234 South Texas VA, Audie Murphy Division San Antonio, Texas, United States, 78284 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.13mL 0.43mL 0.21mL |
10.67mL 2.13mL 1.07mL |
21.35mL 4.27mL 2.13mL |
