Establishment of the active catalytic domain of human PDGFR beta tyrosine kinase-based ELISA assay for inhibitor screening
文献类型：期刊论文
| 作者 | Zhang, Xiu-Hua; Guo, Xiao-Ning; Zhong, Li; Luo, Xiao-Min ; Jiang, Hua-Liang; Lin, Li-Ping; Ding, Jian
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| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
 |
| 出版日期 | 2007-10 |
| 卷号 | 1770期号:10页码:1490-1497 |
| 关键词 | PDGFR beta bac-to-bac system tyrosine kinase inhibitors TKI-30 |
| ISSN号 | 0304-4165 |
| DOI | 10.1016/j.bbagen.2007.06.017 |
| 文献子类 | Article |
| 英文摘要 | Tyrosine kinases are emerging as frequent targets of primary oncogenic events and therefore represent an optimal focus of therapeutic intervention. In an effort towards therapeutic PDGFR inactivation, we expressed the catalytic domain of PDGFR as a soluble active kinase using Bac-to-Bac expression system, and studied the correlations between PDGFR beta activity and enzyme concentration, ATP concentration, substrate concentration and divalent cation type. And a convenient, effective and non-radioactive ELISA screening model is then established for identification of the potential inhibitors targeting PDGFR beta kinase. Of 500 RTK target-based compounds, TKI-30 was identified as a small molecule potential inhibitor of PDGFR beta (IC50=0.34 mu M). Further studies indicated that TKI-30 blocked PDGF-BB-induced autopbosphorylation of PDGFR in a dose-dependent manner in Swiss 3T3 cells and human umbilical vein smooth muscle cells (HLNSMCs). Moreover, it dose-dependently suppressed the PDGF-BB-induced proliferation in HUVSMCs and tube formation of HUVEC. Our data collectively indicated that PDGFR-based ELISA assay is a new method available for screening inhibitors targeting PDGFRO kinase and TKI-30 is a potential novel anti-cancer agent worthy of being further investigated. (c) 2007 Elsevier B.V. All rights reserved. |
| WOS关键词 | ENDOTHELIAL GROWTH-FACTOR ; FACTOR B-CHAIN ; FACTOR RECEPTOR ; PERICYTE RECRUITMENT ; EXPRESSION ; ANTITUMOR ; ANGIOGENESIS ; PURIFICATION ; SUPPRESSION ; CANCER |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000250187600008 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273135]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Ding, Jian |
| 作者单位 | 1.State Key Lab Drug Res, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Xiu-Hua,Guo, Xiao-Ning,Zhong, Li,et al. Establishment of the active catalytic domain of human PDGFR beta tyrosine kinase-based ELISA assay for inhibitor screening[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,2007,1770(10):1490-1497. |
| APA | Zhang, Xiu-Hua.,Guo, Xiao-Ning.,Zhong, Li.,Luo, Xiao-Min.,Jiang, Hua-Liang.,...&Ding, Jian.(2007).Establishment of the active catalytic domain of human PDGFR beta tyrosine kinase-based ELISA assay for inhibitor screening.BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,1770(10),1490-1497. |
| MLA | Zhang, Xiu-Hua,et al."Establishment of the active catalytic domain of human PDGFR beta tyrosine kinase-based ELISA assay for inhibitor screening".BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1770.10(2007):1490-1497. |
入库方式： OAI收割
来源：上海药物研究所
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