1、Product Data SheetVandetanibCat. No.: HY-10260CAS No.: 443913-73-3分式: CHBrFNO分量: 475.35作靶點: VEGFR; Autophagy; Apoptosis作通路: Protein Tyrosine Kinase/RTK; Autophagy; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 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請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內使，-

3、20C 儲存時，請在 1 個內使。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據儲存條件，適當保存；體內實驗的作液，建議您現現配，當天使； 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沉淀、析出現象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 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；然后繼續加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 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，此案不適于實驗周

5、期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 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.戶使本產品發表的科研獻 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