Flavopiridol
产品说明书
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同义名 : | L86-8275;Alvocidib;HL 275;NSC 649890;HMR-1275 |
| CAS号 : | 146426-40-6 | |
| 货号 : | A172904 | |
| 分子式 : | C21H20ClNO5 | |
| 纯度 : | 99%+ | |
| 分子量 : | 401.84 | |
| MDL号 : | MFCD20501884 | |
| 存储条件： |
Pure form Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 35 mg/mL(87.1 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 | Flavopiridol is a pan CDK inhibitor with IC50 value of 30nM, 40nM, 20-40nM, 60nM, 875nM and 20nM for CDK1, 2, 4, 6, 7, 9 (measured by in vitro kinase assays), respectively[1][2]. It can inhibit the whole cell cycle progression through a variety of mechanisms related to CDK inactivation including: 1. Inhibition of CDK4/6 with cyclin D leads to decreased level of pRb-p107 and p130, as well as inactivation of E2F and stop in G1 progression; 2. Inhibition of cdk2 accompanied with cyclin A or E leads to further decreased phosphorylation and inactivation of Rb, as well as inactivation of E2F, and results in retardation in cell cycle progression through the S-phase and accumulation in G1 and G2; 3. Inhibition of CDK1 accompanied with cyclin A or B leads to inhibition of activation of topoisomerase activators, of lamin proteoglycans histone 1 protein and chromatin condensation, as well as results in retardation in cell cycle progression through S-phase and accumulation in G2 phase; 4. Inhibition of cdk7 accompanied with cyclin H complexes leads to reduced activation of cdk’s, such as CDK4 with cyclin D or CDK1 with cyclin B, and reduced activation of RNA polymerase; 5. Flavopiridol may directly influence expression of cyclin D1 and D3 or participate directly in the control of transcription and activation of RNA-polymerase. Flavopiridol is able to induce apoptosis of tumor cells, including leukemia cells, head and neck tumors, breast carcinomas and non-small cell lung carcinoma cell lines, as well as normal cells in vitro after 6–48h with concentration ranging in 0.1–0.4uM[3]. Intraperitoneal treatment of 5mg/kg flavopiridol for 12 days showed antitumor activity in subcutaneous HN12 xenograft mice[4]. Clinical studies of flavopiridol of treatement for advanced solid tumors, ALL, AML, CLL, CML, mantle cell lymphoma, multiple myeloma, non-Hodgkin and other lymphomas, advanced sarcomas, breast, esophageal, head and neck, kidney, ovarian, pancreatic, gastric carcinomas and NSCLC are undergoing[5]. |
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| 作用机制 | Flavopiridol is an ATP-competitive inhibitor[6]. | ||
| 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 cell | Function assay | Inhibition of A2780 cell clonogenic assay， IC50=15 μM | 11063609 | ||
| A2780/DDP-R human ovarian carcinoma cell | Proliferation assay | Inhibition of A2780/DDP-R human ovarian carcinoma cell proliferation, IC50=38 nM | 12190313 | ||
| A2780/DDP-S human ovarian carcinoma cell | Proliferation assay | Inhibition of A2780/DDP-S human ovarian carcinoma cell proliferation, IC50=56 nM | 12190313 | ||
| 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 |
| NCT03604783 | Advanced Solid Tumors | Phase 1 | Not yet recruiting | May 2021 | United States, Wisconsin ... 展开 >> Medical College of Wisconsin Not yet recruiting Milwaukee, Wisconsin, United States, 53226 Contact: Katy C Schroeder, BSN, RN, OCN 414-805-8843 Principal Investigator: Ben George, MD 收起 << |
| NCT00055380 | Cancer | Phase 1 | Completed | - | United States, Maryland ... 展开 >> National Institute of Dental And Craniofacial Research (NIDCR) Bethesda, Maryland, United States, 20892 收起 << |
| NCT00003004 | Unspecified Adult Solid Tumor,... 展开 >> Protocol Specific 收起 << | Phase 1 | Completed | - | United States, New York ... 展开 >> Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10021 收起 << |
| 实验方案 | |||
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| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.49mL 0.50mL 0.25mL |
12.44mL 2.49mL 1.24mL |
24.89mL 4.98mL 2.49mL |
| 参考文献 |
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