Low Molecular Weight Phosphotyrosine Protein Phosphatases as Emerging Targetsfor the Design of Novel Therapeutic Agents

Protein tyrosine phosphorylation is a crucial regulatory event in numerous signaling pathways and is controlled by the concerted and dynamic activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Recent advances in understanding the biological functions of PTPs have revealed complex roles played by these enzymes in important cellular signaling pathways. Moreover, it has been demonstrated that alterations in the expression or activity of several PTPs are implicated in the pathogenesis of serious human diseases, such as diabetes, cancer, inflammatory and cardiovascular pathologies. Out of PTPs that aroused interest as novel drug targets, low molecular weight PTPs (LMW-PTPs) have emerged as attractive targets for designing new agents able to control postreceptor events involved in the development of metabolic and neoplastic pathologies. This Perspective focuses on recent research efforts to identify inhibitors of human LMW-PTP as potential therapeutic agents, also including an outline of the current understanding of the pathophysiological roles of LMW-PTP.