QQ客服 官方微博 反馈留言

	In vitro pharmacological characterization of tki-28, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects
	Guo, XN; Zhong, L; Tan, JZ; Li, J; Luo, XM; Jiang, HL; Nan, FJ; Lin, LP; Zhang, XW; Ding, J
刊名	Cancer biology & therapy
	2005-10-01
卷号	4期号:10页码:1125-1132
关键词	Tyrosine kinase inhibitor Tki-28 Anti-tumor Anti-angiogenesis
ISSN号	1538-4047
通讯作者	Ding, j()
英文摘要	Tyrosine kinases are used as important biomarkers in many tumor types. preclinical and clinical anti-tumor studies have shown that broadly acting tyrosine kinase inhibitors may be more useful than specific inhibitors, since the former might overcome redundancies and crosstalk in tumor cell growth signaling pathways. here, we aim to identify a novel potent tyrosine kinase inhibitor. computer modeling of the pyrido-pyrimidine class compound, tki-28(6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8h-pyrido[2,3-d]pyrimidine7-one), predicted that the compound would dock well in the atp pocket of the erbb-2 tyrosine kinase, yielding a high binding affinity for erbb receptors. biochemical studies revealed that tki-28 potently inhibited the activities of tyrosine kinases such as erbb-2, egfr, kdr, pdgfr b,c-kit and c-src, but had little effect on flt-1 in cell-free system. tki-28 also efficiently blocked autophosphorylation of the listed receptor tyrosine kinases, and subsequently downregulated phosphorylation of many downstream signaling proteins at the cellular level. tki-28 exhibited a more potent anti-proliferative activity against egf- and neuregulin-stimulated sk-ov-3 cells versus serum-stimulated cells, accompanied by apparent induction of apoptosis. finally, tki-28 was found to possess anti-angiogenic effects, characterized by inhibition of cell proliferation driven by egf, vegf and pdgf, as well as decreased cell migration and tube formation in hmecs. these results collectively highlight the pharmacological characteristics of tki-28 as a broad-spectrum tyrosine kinase inhibitor, suggesting that it has great potential as an anti-cancer and anti-angiogenesis agent.
WOS关键词	ADDITIONAL ACTIVITY ; GROWTH-FACTORS ; ZD1839 IRESSA ; CARCINOMA ; TARGETS ; CANCER ; POTENT ; RECEPTORS ; ERBB-2 ; DOMAIN
WOS研究方向	Oncology
WOS类目	Oncology
语种	英语
出版者	LANDES BIOSCIENCE
WOS记录号	WOS:000236043700020
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2377578
专题	中国科学院大学
通讯作者	Ding, J
作者单位	1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci,Div Antitumor Pharmacol, Shanghai Inst Mat Med,State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,Chinese Natl Ctr Drug Scree, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Guo, XN,Zhong, L,Tan, JZ,et al. In vitro pharmacological characterization of tki-28, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects[J]. Cancer biology & therapy,2005,4(10):1125-1132.
APA	Guo, XN.,Zhong, L.,Tan, JZ.,Li, J.,Luo, XM.,...&Ding, J.(2005).In vitro pharmacological characterization of tki-28, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects.Cancer biology & therapy,4(10),1125-1132.
MLA	Guo, XN,et al."In vitro pharmacological characterization of tki-28, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects".Cancer biology & therapy 4.10(2005):1125-1132.

个性服务

查看访问统计

相关权益政策

暂无数据

收藏/分享

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。