Inhibitor Binding Sites in the Protein Tyrosine Phosphatase SHP-2

Haonan Zhang; Zhengquan Gao; Chunxiao Meng; Xiangqian Li; Dayong Shi

doi:10.2174/1389557520666200303130833

Inhibitor Binding Sites in the Protein Tyrosine Phosphatase SHP-2

Mini Rev Med Chem. 2020;20(11):1017-1030. doi: 10.2174/1389557520666200303130833.

Authors

Haonan Zhang¹, Zhengquan Gao¹, Chunxiao Meng¹, Xiangqian Li^{2

3}, Dayong Shi^{2

3}

Affiliations

¹ School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong Province, China.
² State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, Shandong, China.
³ Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China

PMID: 32124695
DOI: 10.2174/1389557520666200303130833

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

Publication types

Review

MeSH terms

Binding Sites / drug effects
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Models, Molecular
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism

Substances

Enzyme Inhibitors
PTPN11 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11