西地尼布作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetCediranibCat. No.: HY-10205CAS No.: 288383-20-0分式: CHFNO分量: 450.51作靶點(diǎn): VEGFR; Autophagy; PDGFR作通路: Protein Tyrosine Kinase/RTK; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) 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制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，

3、請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天 使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可 以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2 mg/mL (4.44 mM); Clear solution此案可獲得 2 mg/

4、mL (4.44 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。Page 1 of 2 www.MedChemEBIOLOGICAL ACTIVITY物活性 Cediranib (AZD2171) 選擇性，有服活性的 VEGFR2 抑制劑，對(duì)Flt1，KDR，F(xiàn)lt4，PDGFR，PDGFR，c-Kit的 IC50 值分別為于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)體外研究 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.體內(nèi)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戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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