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Tivozanib (AV-951)

现货
Catalog No.
A2251
有效的VEGFR选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 940.00
现货
10mg
¥ 850.00
现货
25mg
¥ 1,200.00
现货
100mg
¥ 3,000.00
现货

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Background

Tivozanib is an inhibitor of tyrosine kinase with IC50 value of 160 pmol/L against VEGFR-2 [1].

Tivozanib is a quinoline-urea derivative. As a 2nd generation TKI, it has picomolar potency against VEGFR-1, -2 and -3, and minimal c-kit inhibition. Among this, Tivozanib has demonstrated a VEGFR-2 potency 2 orders of magnitude greater than sunitinib, sorafenib or pazopanib and a lower relative extent of off-target inhibition [1]. Tivozanib also shows to inhibit phosphorylation of the kinases PDGFRß and C-KIT at nanomolar level in cellular assays [2].

Tivozanib has shown antitumor activity in RCC xenograft models in addition to several other solid tumor models leading to its evaluation in clinical testing. The safety and efficacy of Tivozanib has been evaluated in several Phase I and Phase II trials. To compare the front-line use of tivozanib to sorafenib, a pivotal randomized Phase III trial has also been reported [3].

References:
[1] M.N. Fishman, S. Srinivas, R.J. Hauke, R.J. Amato, B. Esteves, M.M. Cotreau, A.L. Strahs, W.J. Slichenmyer, P. Bhargava, F.F. Kabbinavar. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. European Journal of Cancer. 2013(49):2841-2850.
[2] Viktor Grunwald, Axel Stuart Merseburger. The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors – Is there more to come? European Journal of Cancer. 2013(49):2504-2511.
[3] C Lance Cowey. Profile of tivozanib and its potential for the treatment of advanced renal cell carcinoma. Drug Design, Development and Therapy. 2013 (7): 519-527.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt454.86
Cas No.475108-18-0
FormulaC22H19ClN4O5
Solubility≥22.75mg/mL in DMSO
Chemical Name1-[2-chloro-4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea
SDFDownload SDF
Canonical SMILESCC1=CC(=NO1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

人卵巢癌细胞系,包括A2780CP, OVCAR3和SKOV3

溶解方法

在DMSO中的溶解度>22.8mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月

反应时间

10μm, 48h

应用

Tivozanib和EGFR定向治疗的结合表现出细胞生长抑制和诱导凋亡的协同活性,该现象表明抗VEGFR的靶向途径对EGFR定向治疗有敏化作用。

临床实验[2]:

疾病模型

RCC(肾细胞癌)病人

剂量

每日1.5 mg ,3周,口服

应用

Tivozanib表现出对VEGFR家族成员的高敏感性抑制。接受tivozanib治疗的病人有着12.7个月的PFS(无进展生存期),这是在mRCC三期临床中报道的最好的PFS。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Momeny M1, Sabourinejad Z2,3, et al, Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells. Sci Rep. 2017 Apr 6;7:45954. doi: 10.1038/srep45954.

[2]. Grünwald V1, Merseburger AS2. The progression free survival-plateau with vascular endothelial growth factor receptor inhibitors – Is there more to come Eur J Cancer. 2013 Jul;49(11):2504-11. doi: 10.1016/j.ejca.2013.03.022. Epub 2013 Apr 16.

生物活性

Description Tivozanib是一种酪氨酸激酶抑制剂,对VEGFR-2的IC50值为160 pM。
靶点 VEGFR-2          
IC50 160 pM          

质量控制

化学结构

Tivozanib (AV-951)