Inhibiting the Inhibitors, PTP1B as a Therapeutic Target in Myocardial Infarction

Abstract

Mini-Review | Volume 5 | Number 1| 8 Copyright 2018 by Fiedler LR. This is an open-access article distributed under Creative Commons Attribution 4.0 International License (CC BY 4.0), which allows to copy, redistribute, remix, transform, and reproduce in any medium or format, even commercially, provided the original work is properly cited. cc Biological systems self-regulate through cycles of activation and inactivation, the balance of which is critical in permitting or suppressing signaling cascades and their downstream consequences. Kinase signaling pathways are regulated through phosphorylation (activation) and dephosphorylation (inactivation) events. Hyperactivity of kinase pathways plays a causal and critical role in the development of cardiac pathologies, and as such, the development of pharmacological inhibitors has been an intense area of investigation. Conversely, enhancing the activity of suppressed, but potentially beneficial kinase activities present an alternative therapeutic avenue. In this context, kinase dephosphorylation by phosphatases results in inactivation and suppression of the pathway. Thus inhibiting the inhibitors provides a method by which to enhance the activity of selected pathways. The protein tyrosine phosphatase 1B (PTP1B) has been implicated as a therapeutic target in several diseases but was considered to be undruggable. More recent development of inhibitors with improved specificity and pharmacological properties along with identification of novel indications has sparked renewed interest. This mini-review summarises the current status of PTP1B inhibitors in clinical trials and in pre-clinical models for new indications; myocardial infarction and heart failure.