1、Product Data SheetVandetanibCat. No.: HY-10260CAS No.: 443913-73-3分式: CHBrFNO分量: 475.35作靶點(diǎn): VEGFR; Autophagy; Apoptosis作通路: Protein Tyrosine Kinase/RTK; Autophagy; Apoptosis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 : 27.5 mg/mL (57.85 mM; Need ultrasonic an

2、d warming)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.1037 mL 10.5186 mL 21.0371 mL5 mM 0.4207 mL 2.1037 mL 4.2074 mL10 mM 0.2104 mL 1.0519 mL 2.1037 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，-

3、20C 儲(chǔ)存時(shí)，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)娜芙獍浮Ｒ韵氯芙獍付颊?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；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/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: 2.5 mg/mL (5.26 mM); Clear solution此案可獲

4、得 2.5 mg/mL (5.26 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 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。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.26 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.26 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周

5、期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Vandetanib是有效的 VEGFR2 抑制劑，IC50 為40 nM。IC & Target VEGFR240 nM (IC50)體外研究 Vandetanib inhibits VEGFR3 and EGFR with IC50 of 110 nM and 500 nM, respectively. Vandetanib is not sensitive toPDGFR, Flt1, Tie-2 and

6、FGFR1 with IC50 of 1.1-3.6 M, while almost has no activity against MEK, CDK2, c-Kit, erbB2,FAK, PDK1, Akt and IGF-1R with IC50 above 10 M. Vandetanib inhibits VEGF-, EGF- and bFGF-stimulated HUVECproliferation with IC50 of 60 nM, 170 nM and 800 nM, with no effect on basal endothelial cell growth. Va

7、ndetanibinhibits tumor cell growth with IC50 of 2.7 M (A549) to 13.5 M (Calu-6)1. Odanacatib is a weak inhibitor of antigenpresentation, measured in a mouse B cell line (IC50=1.50.4 M), compared to the Cat S inhibitor LHVS (IC50=0.001 M) in the same assay. Odanacatib also shows weak inhibition of th

8、e processing of the MHC II invariant chain proteinIip10 in mouse splenocytes compared to LHVS (minimum inhibitory concentration 1-10 M versus 0.01 M,respectively)2. Vandetanib suppresses phosphorylation of VEGFR-2 in HUVECs and EGFR in hepatoma cells andinhibits cell proliferation4.體內(nèi)研究 Vandetanib (

9、15 mg/kg, p.o.) has a superior anti-tumor effect than gefitinib in the H1650 xenograft model, andsuppresses tumor growth with IC50 of 3.51.2 M3. In tumor-bearing mice, vandetanib (50 or 75 mg/kg) suppressesphosphorylation of VEGFR-2 and EGFR in tumor tissues, significantly reduces tumor vessel densi

10、ty, enhances tumorcell apoptosis, suppresses tumor growth, improves survival, reduces number of intrahepatic metastases, andupregulates VEGF, TGF-, and EGF in tumor tissues4.PROTOCOLCell Assay 3 Growth inhibition is measured by a modified MTT assay. Briefly, the cells are plated on 96-well plates at

11、 a density of2000 cells per well and exposed to each gefitinib or vandetanib for 72 h. Each assay is performed in triplicate. The50% inhibitory concentration (IC50) of each drug is determined as the meanstandard deviation (SD).MCE has not independently confirmed the accuracy of these methods. They a

12、re for reference only.Animal One million H1650 cells or H1650/PTEN cells (H1650 cells with a transfected PTEN gene) are injected subcutaneouslyAdministration 3 into the backs of each mouse. On 10th day after injection, mice are randomLy assigned to three groups, whichreceive either vehicle, vandetan

13、ib (15 mg/kg/day), or gefitinib (15 mg/kg/day). Vehicle, vandetanib, and gefitinib areadministered once per day p.o., five times per week. Tumor volume (width width length/2) and body weight aredetermined periodically. Tumor volumes are expressed as meanSD. Differences in tumor volume are evaluatedu

14、sing Students t-test.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.Page 2 of 3 www.MedChemE Nat Commun. 2020 Apr 20;11(1):1913. Oncogene. 2018 Mar;37(11):1417-1429. Cancer Lett. 2018 Jul 2

15、1;434:184-195. Carbohydr Polym. 2019 Mar 1;207:502-509.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wedge SR, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res.2002 Aug 15;

16、62(16):4645-55.2. Hegedus C, et al. Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications forthe emergence and reversal of cancer drug resistance. Biochem Pharmacol. 2012 Aug 1;84(3):260-7.3. Takeda H, et al. Vandetanib is effective in EGFR-mutant lung cancer cells with PTEN deficiency. Exp Cell Res. 2013 Feb 15;319(4):417-23.4. Inoue K, et al. Vandetanib, an inhibitor of VEGF receptor-2 and EGF receptor, suppresses tumor development and improves prognosis of liver cancer inmice. Clin Cance