Inhibitor binding sites in the protein tyrosine phosphatase SHP-2

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.