产品说明书
Dactolisib
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同义名 : | - |
| CAS号 : | 915019-65-7 | |
| 货号 : | A224243 | |
| 分子式 : | C30H23N5O | |
| 纯度 : | 98+% | |
| 分子量 : | 469.536 | |
| MDL号 : | MFCD10565944 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,Room temperature 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 6 mg/mL(12.78 mM)，配合低频超声，并水浴加热至45℃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 DMF: 2 mg/mL(4.26 mM)，配合低频超声助溶 |
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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 | Aberrant activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin inhibitor (mTOR) signaling pathway promotes the proliferation and survival of various human tumor cells. BEZ235 is a ATP competitive inhibitor of PI3K that inhibits the kinase activity of Class I PI3K p110α/β/δ/γ with IC50 of 4 nM, 75 nM, 7 nM, and 5 nM, respectively. In U87MG glioblastoma cells, the exposure of 0.1 - 1000 nM BEZ235 for 30 min reduced S473P-Akt and T308P-Akt levels in a dose-dependent manner, and the 50% reduction occurred at the doses of 8 nM and 30 nM, respectively. In NWT21 cells, pretreatment of 250 nM BEZ235 reduced insulin-like growth factor-I-induced S473P-Akt level. In starved HT-29 cells, BEZ235 at 250 nM efficiently inhibited interleukin-4-induced S473P-Akt level. The phosphorylation level of mTOR activated kinase p70S6K was significantly reduced by 250 nM BEZ235 in U87MG cells after 30 min incubation. The S235/S236P-RPS6 level in TSC1-null MEF cells was decreased by BEZ235 with an IC50 of 6.5 nM. The addition of BEZ235 (5 - 500 nM) dose-dependently downregulated mTORC1 and mTORC2 activities in IgG-Sepharose pull-downs of HeLa cells. BEZ235 also showed inhibitory effect on cell proliferation. The G1 population of PC3M cells was increased from 66.4% to 74.1% and 92.3% after the treatment with 10 nM and 50 nM BEZ235, respectively. In U87MG tumor-bearing mice, treatment of BEZ235 (25 – 45 mg/kg/d, once daily) for 20 days inhibited tumor growth and reduced S473P-Akt levels in the tumor at a dose-dependent manner[3]. | ||
| 作用机制 | BEZ235 inhibits PI3K via binding to its ATP-binding cleft[3]. | ||
| 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 |
| A3-KAW | Growth Inhibition Assay | IC50=28.64 nM | SANGER | ||
| A427 | Growth Inhibition Assay | IC50=182.57 nM | SANGER | ||
| A431 | Growth Inhibition Assay | IC50=89.97 nM | SANGER | ||
| 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 |
| NCT01285466 | Metastatic or Locally Advanced... 展开 >> Solid Tumors 收起 << | Phase 1 | Completed | - | Belgium ... 展开 >> Novartis Investigative Site Bruxelles, Belgium, 1000 Novartis Investigative Site Bruxelles, Belgium, 1200 Novartis Investigative Site Wilrijk, Belgium, 2610 Germany Novartis Investigative Site Essen, Germany, 45147 Novartis Investigative Site Köln, Germany, 50937 Netherlands Novartis Investigative Site Amsterdam, Netherlands, 1066 CX Spain Novartis Investigative Site Sevilla, Andalucia, Spain, 41013 Novartis Investigative Site Barcelona, Catalunya, Spain, 08035 Switzerland Novartis Investigative Site Chur, Switzerland, 7000 Novartis Investigative Site St. Gallen, Switzerland, 9007 收起 << |
| NCT02430363 | Glioblastoma | Phase 1 Phase 2 | Unknown | June 2018 | United States, Massachusetts ... 展开 >> Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Texas M D Anderson Cancer Center Houston, Texas, United States, 77030 Belgium UCL- Cliniques Universitaires Saint Luc Brussels, Belgium Germany St Johannes Hospital Duisburg, Germany, 47166 Italy Spedali Civili di Brescia Brescia, Italy IRCCS San Raffaele Milan, Italy Poland Lower-Silesian Oncology Centre Wroclaw, Lower-Silesian, Poland, 53413 Russian Federation Pavlov State Medical University St. Petersburg, Russian Federation, 197089 Spain Hospital Universitario Germans Trias I Pujol Barcelona,, Spain Switzerland Universitätsklinik für Frauenheilkunde Bern, Switzerland Ukraine Regional Cancer Center Dnepropetrovsk, Ukraine, 49000 National Institute of Cancer Kiev, Ukraine, 03035 United Kingdom Royal Victoria Hospital Belfast, Ulster, United Kingdom, BT12 6BA 收起 << |
| NCT01508104 | Cancer | Phase 1 | Terminated(funding) | - | United States, Ohio ... 展开 >> University of Cincinnati Cincinnati, Ohio, United States, 45267-0502 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 |
10.65mL 2.13mL 1.06mL |
21.30mL 4.26mL 2.13mL |
| 参考文献 |
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