西地尼布作用机制 - Medchemexpress - MCE中国

1、Product Data SheetCediranibCat. No.: HY-10205CAS No.: 288383-20-0分式: CHFNO分量: 450.51作靶点: VEGFR; Autophagy; PDGFR作通路: Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 49 mg/mL (108.77 mM)H2O : 0.1 mg/mL (insoluble)* means sol

2、uble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.2197 mL 11.0985 mL 22.1971 mL5 mM 0.4439 mL 2.2197 mL 4.4394 mL10 mM 0.2220 mL 1.1099 mL 2.2197 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，

3、请在 1 个内使。体内实验 请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天 使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可 以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2 mg/mL (4.44 mM); Clear solution此案可获得 2 mg/

4、mL (4.44 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。Page 1 of 2 www.MedChemEBIOLOGICAL ACTIVITY物活性 Cediranib (AZD2171) 选择性，有服活性的 VEGFR2 抑制剂，对Flt1，KDR，Flt4，PDGFR，PDGFR，c-Kit的 IC50 值分别为于1， 于3，5，5，36，2nM。IC & Target F

5、lt-1 KDR Flt-4 PDGFR5 nM (IC50) 1 nM (IC50) 3 nM (IC50) 36 nM (IC50)PDGFR c-Kit5 nM (IC50) 2 nM (IC50)体外研究 In human umbilical vein endothelial cells, Cediranib inhibits VEGF-stimulated proliferation and KDR phosphorylationwith IC50 values of 0.4 and 0.5 nM, respectively. In a fibroblast/endothelial

6、cell coculture model of vessel sprouting,Cediranib also reduces vessel area, length, and branching at subnanomolar concentrations1.体内研究 Once-daily oral administration of Cediranib ablates experimental (VEGF-induced) angiogenesis and inhibitsendochondral ossification in bone or corpora luteal develop

7、ment in ovary; physiologic processes that are highlydependent upon neovascularization. The growth of established human tumor xenografts (colon, lung, prostate,breast, and ovary) in athymic mice is inhibited dose-dependently by Cediranib, with chronic administration of 1.5 mgper kg per day producing

8、statistically significant inhibition in all models. A histologic analysis of Calu-6 lung tumorstreated with Cediranib reveals a reduction in microvessel density within 52 hours that becomes progressively greaterwith the duration of treatment. These changes are indicative of vascular regression withi

9、n tumors1.PROTOCOLKinase Assay 1 The inhibitory activity of Cediranib is determined against a range of recombinant tyrosine kinases KDR, Flt-1, Flt-4, c-Kit, PDGFR-, PDGFR-, CSF-1R, Flt-3, FGFR1, Src, Abl, epidermal growth factor receptor (EGFR), ErbB2, Aur-A, andAur-B using ELISA methodology1.MCE h

10、as not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Proliferation of MG63 osteosarcoma cells is induced by PDGF-AA, which selectively activates PDGFR- homodimersignaling. Cells are cultured in DMEM without phenol red containing 1% charcoal stripped

11、FCS, 2 mM glutamine, and1% nonessential amino acids for 24 hours. Cediranib or vehicle is added with PDGF-AA ligand (50 ng/mL) and platesreincubated for 72 hours. Cellular proliferation is determined using a bromodeoxyuridine1.MCE has not independently confirmed the accuracy of these methods. They a

12、re for reference only.Animal Rats: Young female Alderley Park rats (6 weeks of age, Wistar derived, n=5) are dosed orally, once daily for 28 daysAdministration 1 with Cediranib (1.25-5 mg per kg per day) or vehicle. Additional rats (five per group) are treated with Cediranib (5 mgper kg per day) or

13、vehicle for 28 days and maintained for a further 28 days without treatment, to examine the effectof compound withdrawal. Histologic paraffin wax sections of the femorotibial joints and ovaries are stained with H&E.Morphometric image analysis of femorotibial sections is done, with growth plate areas

14、from both the femur and tibiain each joint being combined for an analysis of the effect of compound treatment. The area of corpora lutea in H&E-stained ovary sections is similarly determined by morphometric analysis1.Mice: Mice bearing established Calu-6 human lung tumor xenografts (0.20.01 cm3) are

15、 selected (day 0) and treatedchronically with Cediranib (6 mg per kg per day, p.o.) or vehicle. Tumors are collected (6-15 per group) 4 hours afterthe last dose of Cediranib or vehicle, on days 1, 2, 7, 14, and 21. CD31 is then detected in sections using a chromagenend point or fluorescent immunosta

16、ining1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE户使本产品发表的科研献 Cell Stem Cell. 2019 Sep 5;25(3):373-387.e9. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Biomaterials. 2018 Apr;161:164-178. Neuro Oncol. 2016 Apr;18(4):5

17、38-48. Sci Signal. 2015 Dec 8;8(406):ra125.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wedge SR, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatmentof cancer. Cancer Res, 2005, 65(10), 4389-4400.2. Zhang L, et al. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astroc