首页 工具
登录
购物车
Vandetanib

Vandetanib

产品编号 T1656   CAS 443913-73-3
别名: ZD6474, 凡德他尼

Vandetanib (ZD6474) 是一种具有口服活性的VEGFR2/KDR 酪氨酸激酶抑制剂,IC50值为40 nM。它也抑制VEGFR3/FLT4和EGFR/HER1,IC50值分别为110和500 nM。

TargetMol的所有产品和服务仅用于科学研究,不能被用于人体,我们也不向个人提供产品和服务。
Vandetanib Chemical Structure
Vandetanib, CAS 443913-73-3
规格 价格/CNY 货期 数量
5 mg ¥ 229 现货
10 mg ¥ 372 现货
25 mg ¥ 494 现货
50 mg ¥ 891 现货
100 mg ¥ 1,643 现货
500 mg ¥ 3,671 现货
1 mL * 10 mM (in DMSO) ¥ 413 现货
产品目录号及名称: Vandetanib (T1656)
点击图片重新获取验证码
选择批次  
纯度: 100%
纯度: 99.7%
纯度: 99.68%
更多批次查询请联系客服
生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 (IC50: 40 nM). It also inhibits VEGFR3 and EGFR.
靶点活性 EGFR:500 nM (cell free), VEGFR3:110 nM (cell free), VEGFR2:40 nM (cell free)
体外活性 Vandetanib (ZD6474) is a potent inhibitor of KDR/VEGFR 2 tyrosine kinase activity (IC50: 40 nM). This compound has some additional activity versus the tyrosine kinase activity of VEGFR3 (IC50: 110 nM) and EGFR/HER1 (IC50: 500 nM). The activity of ZD6474 versus KDR tyrosine kinase translates into potent inhibition of VEGF-stimulated endothelial cell (human umbilical vein endothelial cell) proliferation in vitro (IC50: 60 nM) [1]. ZD6474 causes a dose-dependent inhibition of EGFR phosphorylation in mouse NIH-EGFR fibroblasts and human MCF-10A ras breast cancer cells. ZD6474 treatment resulted in a dose-dependent inhibition of soft agar growth in seven human cell lines with functional EGFR but lacking VEGFR-2. A dose-dependent supra-additive effect in growth inhibition and in apoptosis in vitro was observed by the combined treatment with ZD6474 and paclitaxel or docetaxel [2]. Vandetanib and neratinib displayed an inhibitory effect on the basal ABCG2-ATPase. At relatively high concentrations (10–20 mM), vandetanib inhibited the stimulated ABCG2-ATPase [3].
体内活性 Administration of ZD6474 (2.5 mg/kg, i.v.) reversed a hypotensive change induced by VEGF (by 63%) but did not significantly affect that induced by basic fibroblast growth factor. Administration of 50 mg/kg/day ZD6474 (once-daily, p.o.) to athymic mice with intradermally implanted A549 tumor cells also inhibited tumor-induced neovascularization significantly (63% inhibition after 5 days). Histological analysis of Calu-6 tumors treated with 50 mg/kg/day ZD6474 for 24 days showed a significant reduction (>70%) in CD31 (endothelial cell) staining in nonnecrotic regions [1]. ZD6474 treatment of nude mice bearing palpable GEO colon cancer xenografts induced dose-dependent tumor growth inhibition. The antitumor activity of ZD6474 in GEO tumor xenografts was also found to be enhanced when combined with paclitaxel. Tumor regression was observed in all mice after treatment with ZD6474 plus paclitaxel, and it was accompanied by a significant potentiation in the inhibition of angiogenesis [2]. Vandetanib (15 mg/kg) had similar effects on the growth of H1650/PTEN and H1650 parental xenograft tumors [4].
激酶实验 The ability of ZD6474 to inhibit the kinase activity associated with the VEGFRs KDR, Flt-1, and Flt-4 was determined using a previously described ELISA. Briefly, ZD6474 was incubated with enzyme, 10 mm MnCl2, and 2 μm ATP in 96-well plates coated with a poly(Glu, Ala, Tyr) 6:3:1 random copolymer substrate. Phosphorylated tyrosine was then detected by sequential incubation with a mouse IgG anti-phosphotyrosine 4G10 antibody, a horseradish peroxidase-linked sheep anti-mouse immunoglobulin antibody, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid). Microcal Origin software was used to interpolate IC50 values by nonlinear regression. This methodology was adapted to examine selectivity versus tyrosine kinases associated with EGFR, PDGFRβ, Tie-2, FGFR1, c-kit, erbB2, IGF-IR, and FAK. All enzyme assays (tyrosine or serine-threonine) used appropriate ATP concentrations at or just below the respective Km (0.2–14 μm). Selectivity versus serine-threonine kinases (CDK2, AKT, and PDK1) was examined using a relevant scintillation proximity assay (SPA) in 96-well plates. CDK2 assays contained 10 mm MnCl2, 4.5 μm ATP, 0.15 μCi of [γ-33P]ATP/reaction, 50 mm HEPES (pH 7.5), 1 mm DTT, 0.1 mm sodium orthovanadate, 0.1 mm sodium fluoride, 10 mm sodium glycerophosphate, 1 mg/ml BSA fraction V, and a retinoblastoma substrate (part of the retinoblastoma gene, 792–928, expressed in a glutathione S-transferase expression system; 0.22 μm final concentration). Reactions were allowed to proceed at room temperature for 60 min before quenching for 2 h with 150 μl of a solution containing EDTA (62 mm final concentration), 3 μg of a rabbit immunoglobulin anti-glutathione S-transferase antibody and protein A SPA-polyvinyltoluene beads (0.8 mg/reaction). Plates were then sealed, centrifuged (1200 × g for 5 min), and counted on a Topcount NXT Microplate scintillation counter for 30 s [1].
细胞实验 HUVEC proliferation in the presence and absence of growth factors was evaluated using [3H]thymidine incorporation. Briefly, HUVECs isolated from umbilical cords were plated (at passage 2–8) in 96-well plates (1000 cells/well) and dosed with ZD6474 ± VEGF or EGF (3 ng/ml) or bFGF (0.3 ng/ml). The cultures were incubated for 4 days (37°C; 7.5% CO2) and then pulsed with 1 μCi/well [3H]thymidine and reincubated for 4 h. Cells were harvested and assayed for the incorporation of tritium using a beta counter. IC50 data were interpolated as described above [1].
动物实验 Methodology to enable blood pressure measurement in anesthetized rats was as described previously. Briefly, anesthesia was induced in male Alderley Park rats using α-chloralose by the i.v. route and then maintained with thiopentone via the i.p. route. Once surgical anesthesia was established, the carotid artery was cannulated to enable blood pressure recording using a pressure transducer and a Lectromed MT8P amplifier. The jugular vein was cannulated to allow growth factor administration. Body temperature was maintained with a thermostatically controlled heated blanket coupled to a rectal thermometer. Human VEGF165 (32 μg/kg) or bFGF (40 μg/kg) was administered as a bolus injection [0.1 ml/250 g body weight in 0.85% (w/v) sodium chloride], and a maximal blood pressure drop was recorded within 2 min (typically 26–30 mm Hg). These changes were sustainable for more than 20 min in control experiments. ZD6474 (2.5 mg/kg) or vehicle alone [25% (w/v) hydroxypropyl-β-cyclodextrin in Sorensons phosphate buffer (pH 5.5)] was administered i.v., and blood pressure was recorded 5 min later to determine the effect on growth factor-induced hypotension [1].
别名 ZD6474, 凡德他尼
分子量 475.35
分子式 C22H24BrFN4O2
CAS No. 443913-73-3

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 27.5 mg/mL (57.85 mM), Sonification is recommended

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.1037 mL 10.5186 mL 21.0371 mL 52.5928 mL
5 mM 0.4207 mL 2.1037 mL 4.2074 mL 10.5186 mL
10 mM 0.2104 mL 1.0519 mL 2.1037 mL 5.2593 mL
20 mM 0.1052 mL 0.5259 mL 1.0519 mL 2.6296 mL
50 mM 0.0421 mL 0.2104 mL 0.4207 mL 1.0519 mL

TargetMol Calculator计算器

摩尔浓度计算器
稀释计算器
配液计算器
分子量计算器
=
X
X
X
=
X
=
/
g/mol

输入分子式,点击计算,可计算出产品的分子量。

TargetMol Library Books参考文献

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. Ciardiello F, et al. Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin Cancer Res. 2003 Apr;9(4):1546-56. 3. 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. 4. 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. 5. Chang Z, Zhang Y, Liu J, et al. Snail promotes the generation of vascular endothelium by breast cancer cells[J]. Cell Death & Disease. 2020, 11(6): 1-17.

TargetMol Library Books文献引用

1. Jin Y, Chen X, Gao Z, et al. Bisdemethoxycurcumin alleviates vandetanib-induced cutaneous toxicity in vivo and in vitro through autophagy activation. Biomedicine & Pharmacotherapy. 2021, 144: 112297. 2. Chang Z, Zhang Y, Liu J, et al. Snail promotes the generation of vascular endothelium by breast cancer cells. Cell Death & Disease. 2020, 11(6): 1-17
Alpha-Hederin Bruceine D BMS-833923 CCI-007 Serdemetan Exisulind PD0166285 DB1976

相关化合物库

该产品包含在如下化合物库中:
抑制剂库 EMA 上市药物库 抗癌上市药物库 抗癌活性化合物库 膜蛋白靶向化合物库 FDA 上市激酶抑制剂库 抗癌药物库 激酶抑制剂库 抗癌临床化合物库 药物功能重定位化合物库

TargetMol Calculator剂量换算

对于不同动物的给药剂量换算,您也可以参考 更多...

TargetMol Calculator 体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。

体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
g
给药体积
μL
动物数量
第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
% DMSO
%
% Tween 80
% ddH2O
计算 重置

技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

Vandetanib 443913-73-3 Angiogenesis Apoptosis Autophagy JAK/STAT signaling Tyrosine Kinase/Adaptors EGFR VEGFR inhibit ZD6474 Vascular endothelial growth factor receptor 凡德他尼 Inhibitor ZD-6474 ZD 6474 inhibitor

 

TargetMol Loading
陶术
生物
TargetMol®中国区唯一合作伙伴
点击进入陶术生物官网陶术生物
联系我们
400-820-0310

上海市静安区江场三路238号8楼