产品说明书
Danusertib
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同义名 : | PHA-739358 |
| CAS号 : | 827318-97-8 | |
| 货号 : | A395008 | |
| 分子式 : | C26H30N6O3 | |
| 纯度 : | 99%+ | |
| 分子量 : | 474.555 | |
| MDL号 : | MFCD12024692 | |
| 存储条件： |
粉末 Sealed in dry,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: 50 mg/mL(105.36 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： |
| 生物活性 | |||
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| 靶点 |
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| 描述 | The Aurora family of serine/threonine kinases, which consists of Aurora A, B and C, plays an important role in chromosome alignment, segregation, and cytokinesis during mitosis. Danusertib is pan-Aurora inhibitor with IC50 values of 13, 79, and 61 nM for Aurora A, B, and C (measured by in vitro kinase assays), respectively, also shows inhibitory effect on Abl, TrkA, c-RET and FGFR1 with IC50 values of 25nM, 31nM, 31nM and 47nM, respectively. Treatment with Danusertib below 10μM inhibited autophosphorylation in position Thr288 of Aurora A and histone H3 in position Ser10, the substrate of Aurora B, suggesting the cellular inhibition on Aurora A and Aurora B kinase activity by Danusertib in HeLa cells. Consistent with the in vitro kinase assays, the inhibition on c-RET, TrkA and FGFR1 by Danusertib can be observed, performing by the decreased pRet-Y905 in TT cells, decreased pTrkA-Y490 induced by NGF in PC-12 cells and decreased pERK1/2 of FGFR1 downstream induced by FGF not EGF in NIH-3T3 cells. Danusertib showed widely antiproliferative effect with IC50 values ranging in 28-300nM in several tumor cell lines covering different histotypes, including colon, breast, prostate, lung, and ovary. This anti-proliferation by Danusertib may due to both inhibition of Aurora B and defects of the p53-p21–dependent postmitotic checkpoint, and these markers can also be observed in in vivo study. Administration of Danusertib at dose of 25-30 mg/kg, i.v., bd, showed antitumor activity in several human tumor xenograft models, including HL-60, A2780, HCT-116, DMBA-induced mammary carcinoma, MMTV-RAS transgenic mammary carcinoma and TRAMP transgenic prostate carcinoma[1]. | ||
| 作用机制 | Danusertib is a small molecule ATP competitive pan-aurora kinase inhibitor.[2] | ||
| 细胞研究 | |||||
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| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| A2780 cells | Proliferation assay | Antiproliferative activity against A2780 cells, IC50=28 nM | 17125279 | ||
| HCT116 cells | Proliferation assay | Antiproliferative activity against HCT116 cells, IC50=31 nM | 17125279 | ||
| HCT116 cells | Function assay | Cell cycle arrest in HCT116 cells by accumulation at G2/M phase, EC50=80 nM | 17125279 | ||
| 临床研究 | |||||
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| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT00335868 | Leukemia | Phase 2 | Unknown | - | United States, California ... 展开 >> Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California, United States, 90095-1781 收起 << |
| NCT00766324 | Metastatic Hormone Refractory ... 展开 >>Prostate Cancer 收起 << | Phase 2 | Completed | - | Italy ... 展开 >> Nerviano Medical Sciences. Clinical Research Dept. Nerviano, Milano, Italy, 20014 收起 << |
| NCT00872300 | Multiple Myeloma | Phase 2 | Terminated(Low recruitment rat... 展开 >>e) 收起 << | - | United States, Arizona ... 展开 >> MAYO Clinic Scottsdale, Arizona, United States, 85259 United States, Illinois The Robert H Lurie Comprehensive Cancer Center, Northwestern University Chicago, Illinois, United States, 60611 France Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille Lille, France, 59037 University Hospital Hôtel-Dieu Nantes, France, 44093 收起 << |
| 实验方案 | |||
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| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.11mL 0.42mL 0.21mL |
10.54mL 2.11mL 1.05mL |
21.07mL 4.21mL 2.11mL |
| 参考文献 |
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