Protein tyrosine phosphatase inhibition by metals and metal complexes.

SIGNIFICANCE: Protein tyrosine phosphatases (PTPs) play essential roles in controlling cell proliferation, differentiation, communication, and adhesion. The dysregulated activities of PTPs are involved in the pathogenesis of a number of human diseases such as cancer, diabetes, and autoimmune diseases. RECENT ADVANCES: Many PTPs have emerged as potential new targets for novel drug discovery. PTP inhibitors have attracted much attention. Many PTP inhibitors have been developed. Some of them have been proven to be efficient in lowering blood glucose levels in vivo or inhibiting tumor xenograft growth. CRITICAL ISSUES: Some metal ions and metal complexes potently inhibit PTPs. The metal atoms within metal complexes play an important role in PTP binding, while ligand structures influence the inhibitory potency and selectivity. Some metal complexes can penetrate the cell membrane and selectively bind to their targeting PTPs, enhancing the phosphorylation of the related substrates and influencing cellular metabolism. PTP inhibition is potentially involved in the pathophysiological and toxicological processes of metals and some PTPs may be cellular targets of certain metal-based therapeutic agents. FUTURE DIRECTIONS: Investigating the structural basis of the interactions between metal complexes and PTPs would facilitate a comprehensive understanding of the structure-activity relationship and accelerate the development of promising metal-based drugs targeting specific PTPs.