Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders

The aim of this review was to discuss an overview of type 2 diabetes; biology of PTP1B; role of PTP1B in metabolic disorders; and recent updates in the development of PTP1B inhibitors reported in literature since 1994. In this study, extensive literature search was carried out on PTP1B inhibitors of natural as well as synthetic origin in various scientific databases and research articles related to discovery of PTP1B inhibitors were selected for this study. Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target for several human diseases including type 2 diabetes, obesity and cancer because of its seminal part as a negative modulator in both insulin and leptin signaling pathways. A large number of molecules of broad chemical diversity were reported as potent and selective PTP1B inhibitors over other protein tyrosine phosphatases. Several of these molecules have shown their potential in the treatment of various human diseases including type 2 diabetes, obesity, inflammation and cancer in various animal models. But only a very limited number of PTP1B inhibitors (including ertiprotafib, trodusquemine and JTT-551) has entered clinical trials and are finally withdrawn owing to their unsatisfactory effectiveness and undesirable adverse effects. Consequently, it is still highly imperative and of great importance to develop potent, highly selective and safe PTP1B inhibitors.