CuAAC Click Chemistry Accelerates the Discovery of Novel Chemical Scaffolds as Promising Protein Tyrosine Phosphatases Inhibitors
X. -P. He, J. Xie, Y. Tang, J. Li and G. -R. Chen
Pages 2399-2405 (7)
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 azidealkyne 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.
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
Key Laboratory for Advanced Materials & Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, P.R. China.