文献类型：期刊文献

英文题名：CuAAC Click Chemistry Accelerates the Discovery of Novel Chemical Scaffolds as Promising Protein Tyrosine Phosphatases Inhibitors

作者：He, X. -P.[1,2];Xie, J.[4];Tang, Y.[1,2];Li, J.[3];Chen, G. -R.[1,2]

机构：[1]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening,State Key Lab Drug Res, Shanghai 201203, Peoples R China;[4]CNRS, UMR 8531, Inst Alembert, PPSM,ENS Cachan, F-94235 Cachan, France

年份：2012

卷号：19

期号：15

起止页码：2399

外文期刊名：CURRENT MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000303130200009)】；

基金：We gratefully acknowledge the National Natural Science Foundation of China (Grants 21176076 and 81125023), Shanghai Committee of Science and Technology (Grant 10410702700) and the Fundamental Research Funds for the Central Universities (No. WK1013002) for generously providing the funding. Dr. X.-P. He is also supported by China Postdoctoral Science Foundation (No. 2011M500069) and he warmly acknowledges the French Embassy in PR China for providing a co-tutored doctoral scholarship and ENS Cachan.

语种：英文

外文关键词：Protein tyrosine phosphatase; click chemistry; in situ screening; drug discovery; CuAAC; tyrosine phosphorylation; dephosphorylation; carbohydrate; amino acid; salicylic acid; isoxazole acid; ketocarboxylic acid; competitive inhibitor; bidentate

摘要：Protein tyrosine phosphatases (PTPs) are crucial regulators for numerous biological processes in nature. The dysfunction and overexpression of many PTP members have been demonstrated to cause fatal human diseases such as cancers, diabetes, obesity, neurodegenerative diseases and autoimmune disorders. In the past decade, considerable efforts have been devoted to the production of PTPs inhibitors by both academia and the pharmaceutical industry. However, there are only limited drug candidates in clinical trials and no commercial drugs have been approved, implying that further efficient discovery of novel chemical entities competent for inhibition of the specific PTP target in vivo remains yet a challenge. In light of the click-chemistry paradigm which advocates the utilization of concise and selective carbon-heteroatom ligation reactions for the modular construction of useful compound libraries, the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction (CuAAC) has fueled enormous energy into the modern drug discovery. Recently, this ingenious chemical ligation tool has also revealed efficacious and expeditious in establishing large combinatorial libraries for the acquisition of novel PTPs inhibitors with promising pharmacological profiles. We thus offer here a comprehensive review highlighting the development of PTPs inhibitors accelerated by the CuAAC click chemistry.