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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Mini-Review Article

Inhibitor Binding Sites in the Protein Tyrosine Phosphatase SHP-2

Author(s): Haonan Zhang, Zhengquan Gao, Chunxiao Meng*, Xiangqian Li* and Dayong Shi*

Volume 20, Issue 11, 2020

Page: [1017 - 1030] Pages: 14

DOI: 10.2174/1389557520666200303130833

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Abstract

Protein tyrosine phosphatase 2 (SHP-2) has long been proposed as a cancer drug target. Several small-molecule compounds with different mechanisms of SHP-2 inhibition have been reported, but none are commercially available. Pool selectivity over protein tyrosine phosphatase 1 (SHP-1) and a lack of cellular activity have hindered the development of selective SHP-2 inhibitors. In this review, we describe the binding modes of existing inhibitors and SHP-2 binding sites, summarize the characteristics of the sites involved in selectivity, and identify the suitable groups for interaction with the binding sites.

Keywords: PTP, SHP-2, SHP-1, protein tyrosine kinases, PTKs, cancer.

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