Vandetanib (D6474) is a potent, orally active inhibitor of VEGFR2/KDR tyrosine kinase activity (IC₅₀=40 nM). Vandetanib also has activity versus the tyrosine kinase activity of VEGFR3/FLT4 (IC₅₀=110 nM) and EGFR/HER1 (IC₅₀=500 nM)^[1].

Vandetanib inhibits VEGFR3 and EGFR with IC₅₀ of 110 nM and 500 nM, respectively. Vandetanib is not sensitive to PDGFRβ, Flt1, Tie-2 and FGFR1 with IC₅₀ of 1.1-3.6 μM, while almost has no activity against MEK, CDK2, c-Kit, erbB2, FAK, PDK1, Akt and IGF-1R with IC₅₀ above 10 μM. Vandetanib inhibits VEGF-, EGF- and bFGF-stimulated HUVEC proliferation with IC₅₀ of 60 nM, 170 nM and 800 nM, with no effect on basal endothelial cell growth. Vandetanib inhibits tumor cell growth with IC₅₀ of 2.7 μM (A549) to 13.5 μM (Calu-6)^[1]. Odanacatib is a weak inhibitor of antigen presentation, measured in a mouse B cell line (IC₅₀=1.5±0.4 μM), compared to the Cat S inhibitor LHVS (IC₅₀=0.001 μM) in the same assay. Odanacatib also shows weak inhibition of the processing of the MHC II invariant chain protein Iip10 in mouse splenocytes compared to LHVS (minimum inhibitory concentration 1-10 μM versus 0.01 μM, respectively)^[2]. Vandetanib suppresses phosphorylation of VEGFR-2 in HUVECs and EGFR in hepatoma cells and inhibits cell proliferation^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Vandetanib (15 mg/kg, p.o.) has a superior anti-tumor effect than gefitinib in the H1650 xenograft model, and suppresses tumor growth with IC₅₀ of 3.5±1.2 μM^[3]. In tumor-bearing mice, vandetanib (50 or 75 mg/kg) suppresses phosphorylation of VEGFR-2 and EGFR in tumor tissues, significantly reduces tumor vessel density, enhances tumor cell apoptosis, suppresses tumor growth, improves survival, reduces number of intrahepatic metastases, and upregulates VEGF, TGF-α, and EGF in tumor tissues^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

475.35

C₂₂H₂₄BrFN₄O₂

443913-73-3

凡德他尼

Room temperature in continental US; may vary elsewhere.

DMSO : 27.5 mg/mL (57.85 mM; Need ultrasonic and warming)

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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方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，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.26 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.26 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.26 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.26 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Wedge SR, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;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 for the 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 in mice. Clin Cancer Res. 2012 Jul 15;18(14):3924-33.

Growth inhibition is measured by a modified MTT assay. Briefly, the cells are plated on 96-well plates at a density of 2000 cells per well and exposed to each gefitinib or vandetanib for 72 h. Each assay is performed in triplicate. The 50% inhibitory concentration (IC₅₀) of each drug is determined as the mean±standard deviation (SD).

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

One million H1650 cells or H1650/PTEN cells (H1650 cells with a transfected PTEN gene) are injected subcutaneously into the backs of each mouse. On 10th day after injection, mice are randomLy assigned to three groups, which receive either vehicle, vandetanib (15 mg/kg/day), or gefitinib (15 mg/kg/day). Vehicle, vandetanib, and gefitinib are administered once per day p.o., five times per week. Tumor volume (width × width × length/2) and body weight are determined periodically. Tumor volumes are expressed as mean±SD. Differences in tumor volume are evaluated using Student’s t-test.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Wedge SR, et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;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 for the 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 in mice. Clin Cancer Res. 2012 Jul 15;18(14):3924-33.