产品说明书
Cediranib
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同义名 : | AZD2171;ZD 2171;NSC-732208 |
| CAS号 : | 288383-20-0 | |
| 货号 : | A368855 | |
| 分子式 : | C25H27FN4O3 | |
| 纯度 : | 99%+ | |
| 分子量 : | 450.505 | |
| MDL号 : | MFCD09954115 | |
| 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: 18 mg/mL(39.96 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 | VEGF/VEGFR (vascular endothelial growth factor vascular endothelial growth factor receptor) pathway plays a key role in tumor angiogenesis by promotion of vascular and lymphatic endothelial, as well as survival, and invasion, thus resulting in neovascularization, tumor growth and metastasis. In addition, blockade of additional proangiogenic receptor tyrosine kinases, including PDGFR and FGFR, may improve long-term clinical outcomes. Cediranib is a multiple RTKs inhibitor with IC50 values of <0.001μM, 0.005μM, ≤0.003μM, 0.002μM and 0.005μM for VEGFR-2, VEGFR-1, VEGFR-3, c-Kit and PDGFR-β(measured kinase activity), respectively, less potent to PDGFR-α, CSF-1R, FGFR1, Src and Abl with IC50 values of 0.036nM, 0.11nM, 0.026nM, 0.13nM and 0.26nM, respectively. The kinase activity inhibition by Cediranib can be observed through the suppression of phosphorylation on KDR (HUVEC), c-Kit (NCI-H526), PDGFR-α (MG63), PDGFR-β (MG63), CSF-1R (NIH3T3/CSF1R) and EGFR (KB) with IC50 values of 0.0005, 0.001, 0.005, 0.008, 0.21 and 1.1μM, respectively, in cellular study. Consistent with its selectivity on VEGFR, Cediranib inhibited VEGF-stimulated HUVEC proliferation most potently with IC50 value of 0.4nM, versus IC50 values of 110nM/500nM for bFGF-/EGF-induced HUVEC proliferation, as well as 40nM PDGF-induced MG63 proliferation. Also through the inhibition of VEGFR, Cediranib inhibited vessel branching, length, and area with mean IC50 values of 0.1nM, 0.1nM and 0.2nM in in vitro study, as well as completely abolished VEGF-driven angiogenesis at 6mg/kg/day in in vivo models. The effect of Cediranib-induced hypertrophy in bone growth plate and inhibition on luteal development in ovary (5mg/kg, orally) further confirmed its inactivation of VEGF-induced angiogenesis within complex physiologic settings. Cediranib showed broad-spectrum anti-tumor activity as oral administration of Cediranib at dose of 1.5,3 and 6mg/kg once daily inhibited growth of all human tumor xenografts examined, including SW620 (colon), Calu-6 (lung), PC-3 (prostate), MDA-MB-231 (breast) and SKOV-3 (ovary), with vascular regression observed in Calu-6 lung tumor xenografts at dose of 6mg/kg[1]. | ||
| 作用机制 | Cediranib is an ATP-competitive inhibitor of KDR tyrosine kinase.[1] | ||
| 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 |
| HUVEC cell | Proliferation assay | 3 days | Inhibition of VEGF-stimulated HUVEC cell proliferation treated before 2 hrs of VEGF challenge assessed after 3 days by [3H]thymidine incorporation assay, ED50=12 nM | 19101155 | |
| 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 |
| NCT00691730 | Unspecified Adult Solid Tumor,... 展开 >> Protocol Specific 收起 << | Not Applicable | Active, not recruiting | December 2018 | Canada, Alberta ... 展开 >> Tom Baker Cancer Centre Calgary, Alberta, Canada, T2N 4N2 Canada, Ontario London Regional Cancer Program London, Ontario, Canada, N6A 4L6 Mount Sinai Hospital Toronto, Ontario, Canada, M5G 1X5 University Health Network-Princess Margaret Hospital Toronto, Ontario, Canada, M5G 2M9 收起 << |
| NCT00310089 | Breast Cancer | Not Applicable | Completed | - | United States, Maryland ... 展开 >> Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland, United States, 20892-1182 United States, New Jersey Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey, United States, 08903 收起 << |
| NCT02910843 | Rectal Cancer | Phase 1 | Recruiting | December 2022 | Switzerland ... 展开 >> St. Claraspital Basel Recruiting Basel, Switzerland, 4016 Contact: Dieter Köberle, MD +41 61 685 85 85 dieter.koeberle@claraspital.ch Principal Investigator: Dieter Köberle, MD Universitätsspital Basel Recruiting Basel, Switzerland, 4031 Contact: Viviane Hess, Prof +41 61 265 50 74 viviane.hess@usb.ch Principal Investigator: Viviane Hess, Prof Inselspital Bern Recruiting Bern, Switzerland, 3010 Contact: Martin D. Berger, MD +41 31 632 41 14 martin.berger@insel.ch Principal Investigator: Martin D. Berger, MD Kantonsspital Graubünden Recruiting Chur, Switzerland, 7000 Contact: Ioannis Metaxas, MD +41 81 256 66 46 ioannis.metaxas@ksgr.ch Principal Investigator: Ioannis Metaxas, MD Kantonsspital Luzern Recruiting Luzern, Switzerland, 6000 Contact: Ralph Winterhalder, MD +41 41 205 58 75 ralph.winterhalder@ksl.ch Principal Investigator: Ralph Winterhalder, MD Kantonsspital St. Gallen Recruiting St. Gallen, Switzerland, 9007 Contact: Markus Jörger, MD +41 71 494 29 22 markus.joerger@kssg.ch Principal Investigator: Markus Jörger, MD UniversitätsSpital Zürich Recruiting Zurich, Switzerland, 8091 Contact: Bernhard Pestalozzi, Prof +41 (0)44 255 34 40 bernhard.pestalozzi@usz.ch Principal Investigator: Bernhard Pestalozzi, Prof 收起 << |
| 实验方案 | |||
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| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.22mL 0.44mL 0.22mL |
11.10mL 2.22mL 1.11mL |
22.20mL 4.44mL 2.22mL |
