产品说明书
Alisertib
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同义名 : | MLN 8237 |
| CAS号 : | 1028486-01-2 | |
| 货号 : | A102516 | |
| 分子式 : | C27H20ClFN4O4 | |
| 纯度 : | 99%+ | |
| 分子量 : | 518.923 | |
| MDL号 : | MFCD16621243 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 25 mg/mL(48.18 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+30% PEG300+water 1.6 mg/mL clear PO 0.5% CMC-Na 36 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 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. Alisertib is a selective Aurora A kinase inhibitor with IC50 value of 1.2nM versus 396.5nM for Aurora B (measured by enzymatic assay). Consistent with inhibition by Aurora A on cell phenotype, treatment with 50nM Alisertib casued an increase in cells in the G2/M phase at 24 and 48 hours in HCT-116 cells, as well as caused mitotic spindle abnormalities and chromosome misalignment in cells. However, at a higher concentration of 0.25 or 1μM, Alisertib caused an increase in the number of cells with 8N DNA content and multinuclear in cells, as phenotypes consistent with Aurora B inhibition. Alisertib can inhibit cell proliferation, including HCT-116, SW480, DLD-1, H460, MDA-MB-231, PC3, SKOV3, HPAC, OCI-LY-3, OCI-LY-7, OCI-LY-10, OCI-LY-19 and WSU cell lines, with IC50 values ranging in 15-469nM, suggesting its widely anti-proliferative effect on colon, lung, breast, prostate, ovarian, pancreatic and lymphoma tumor. Alisertib possessed good pharmacodynamics as orally dosed at 3, 10, and 30mg/kg with Alisertib resulted in a time- and dose-dependent increase in the mitotic marker p-HisH3, suggesting Aurora A inhibition, in tumor tissue from HCT-116 xenografts. Misaligned chromosomes and reduced bipolar mitotic spindles can also be observed. Oral administration of Alisertib at 3, 10, and 30 mg/kg once daily for 21 consecutive days dose-dependently inhibit tumor growth in nude mice bearing subcutaneous HCT-116 tumors. The broad antitumor activity of Alisertib can also be observed in a diverse set of solid tumor xenograft models as well as regressions in in vivo models of lymphoma, including the cell lines mentioned above[1]. | ||
| 作用机制 | Alisertib binds Aurora-A at the ATP-binding pocket.[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 |
| 2884 | 100 μM | Growth Inhibition Assay | 72 h | Attenuates cell growth | 23328114 |
| 2885 | 100 μM | Growth Inhibition Assay | 72 h | Attenuates cell growth | 23328114 |
| A172 | 100 μM | Cytotoxic Assay | 24 h | IC50=0.120 μM | 22274399 |
| 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 |
| NCT02551055 | Neoplasms, Advanced or Metasta... 展开 >>tic 收起 << | Phase 1 | Terminated(Business Decision; ... 展开 >>No Safety Or Efficacy Concerns.) 收起 << | - | United States, New York ... 展开 >> Lake Success, New York, United States New York, New York, United States United States, Pennsylvania Philadelphia, Pennsylvania, United States United States, Texas Dallas, Texas, United States Houston, Texas, United States Spain Barcelona, Spain 收起 << |
| NCT01540682 | Head and Neck Cancer | Phase 1 | Completed | - | United States, Pennsylvania ... 展开 >> Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104 收起 << |
| NCT01316692 | Recurrent Melanoma ... 展开 >> Stage IIIc Melanoma Stage IV Melanoma 收起 << | Phase 2 | Terminated(low accrual) | - | United States, Tennessee ... 展开 >> Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232-6838 收起 << |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
1.93mL 0.39mL 0.19mL |
9.64mL 1.93mL 0.96mL |
19.27mL 3.85mL 1.93mL |
| 参考文献 |
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