1. Protein tyrosine phosphatase 1B in metabolic diseases and drug development.
- Author
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Delibegović M, Dall'Angelo S, and Dekeryte R
- Subjects
- Humans, Animals, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Enzyme Inhibitors therapeutic use, Enzyme Inhibitors pharmacology, Signal Transduction drug effects, Obesity drug therapy, Obesity metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 1 antagonists & inhibitors, Protein Tyrosine Phosphatase, Non-Receptor Type 1 metabolism, Drug Development, Metabolic Diseases drug therapy, Metabolic Diseases metabolism
- Abstract
Protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane phosphatase, has a major role in a variety of signalling pathways, including direct negative regulation of classic insulin and leptin signalling pathways, and is implicated in the pathogenesis of several cardiometabolic diseases and cancers. As such, PTP1B has been a therapeutic target for over two decades, with PTP1B inhibitors identified either from natural sources or developed throughout the years. Some of these inhibitors have reached phase I and/or II clinical trials in humans for the treatment of type 2 diabetes mellitus, obesity and/or metastatic breast cancer. In this Review, we summarize the cellular processes and regulation of PTP1B, discuss evidence from in vivo preclinical and human studies of the association between PTP1B and different disorders, and discuss outcomes of clinical trials. We outline challenges associated with the targeting of this phosphatase (which was, until the past few years, viewed as difficult to target), the current state of the field of PTP1B inhibitors (and dual phosphatase inhibitors) and future directions for manipulating the activity of this key metabolic enzyme., (© 2024. Springer Nature Limited.)
- Published
- 2024
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