Tivozanib (AV-951)(VEGFR-1/VEGFR-2/VEGFR-3/c-Kit/PDGFRYZ剂)

Kinasechem是来自英国的专业的YZ剂供应商，提供覆盖几百个激酶靶点的YZ剂。 Kinasechem的产品涉及绝大多数的信号通路研究以及癌症研究，包括： PI3K-Akt signaling pathway； MAPK signaling pathway; apoptosis(凋亡)； DNA damage( DNA 损伤) RTK(受体酪氨酸激酶） 等YZ剂在生命科学研究领域的应用非常广泛。在信号通路以及癌症研究方面，很多地方需要用到YZ剂来阻抑信号通路。目前，在HIV的研究，抗感染，心血管疾病，老年痴呆症（阿兹海默症），甚至糖尿病的研究中，都会使用到YZ剂。 1、 YZ剂的一般使用方法：（1）细胞实验将YZ剂溶解于DMSO, 乙醇或者水中，稀释到需要的浓度。一般孵育48小时，也有孵育2周的实验。（2）动物实验小鼠模型：以注射为主。大鼠模型：以口服为主。（3）抗药性筛选实验长期孵育，递增性增加浓度。 2、YZ剂的几个重要参数： IC50(半YZ浓度) 指YZ剂降低对应激酶的活性到原来活性的一半的浓度。 IC50是YZ剂一个重要的指标，一般而言，IC50越小，YZ能力越强。 EC50 指加入YZ剂后，细胞死亡一半所需的浓度。 YZ剂选择性YZ剂有多重YZ剂，指同时YZ多个靶点的YZ剂。有高选择性YZ剂，仅仅YZ某些激酶的某个亚型或者结构域。比如，有的YZ剂仅仅YZPI3K这个激酶的gamma亚型。
Information
 

SKU:K1176		M. Wt:454.86
Formula:C22H19ClN4O5		Solubility:DSMO 20 mg/mL Water <1 mg/ml Ethanol <1 mg/ml
Purity:>99%		Storage:2 years at -20 degrees centigrade
CAS No.:475108-18-0
Chemical Name1-(2-chloro-4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-3-(5-methylisoxazol-3-yl)urea

Biological Activity
 

Description	Tivozanib (AV-951; KRN-951) is able to markedly inhibit VEGFR-1, VEGFR-2, VEGFR-3, c-Kit and PDGFR with IC50 of 0.21, 0.16, 0.24, 1.63 and 1.72 nM.
Targets	VEGFR-1	VEGFR-2	VEGFR-3	c-Kit	PDGFR
IC50	0.21 nM	0.16 nM	0.24 nM	1.63 nM	1.72 nM
In vitro	As an orally active, ATP-competitive, small-molecule, quinoline-urea derivative , Tivozanib (AV-951; KRN-951) is able to markedly inhibit VEGFR-1, VEGFR-2, VEGFR-3, c-Kit and PDGFR with IC50 of 0.21, 0.16, 0.24, 1.63 and 1.72 nM, respectively.
IN vivo	Tivozanib produced a significant inhibition of tumor growth and angiogenesis in several different xenograft tumor models in athymic rats.[1] In a phase I clinical trial, tivozanib was safe and tolerable when administered at oral doses up to 1.5 mg on a schedule of 4 weeks on, 2 weeks off treatment. Results from a phase II clinical trial in patients with advanced renal cell carcinoma reported an overall response rate of 25.4% and a median progression-free survival of 11.8 months in patients treated with tivozanib as a single agent.[1] In a Phase II Randomized Discontinuation proved that tivozanib was active and well tolerated in patients with advanced RCC and supported additional development of tivozanib in advanced RCC. [2]