Inhibiting the Inhibitors, PTP1B as a Therapeutic Target in Myocardial Infarction
DOI:
https://doi.org/10.17140/HROJ-5-147Keywords:
Myocardial infarction, Phosphatase inhibitors, PTP1BAbstract
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.
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