Abstract
Diabetes is a prevalent disease which effects over 150 million people worldwide and there is a great medical need for new therapeutic agents to treat it. Inhibition of protein tyrosine phosphatase 1B (PTP1B) has emerged as a highly validated, attractive target for treatment of not only diabetes but also obesity. Discovery of small-molecule inhibitors has been pursued extensively in both academia and industry and a number of very potent and selective inhibitors have been identified. With X-ray crystallography, the binding interactions of several classes of inhibitors have been elucidated. This has resulted in significant progress in understanding important interactions between inhibitors and specific residues of PTP1B, which could help the design of future inhibitors. However, since the active site of PTP1B that most of these inhibitors bind to is highly hydrophilic, it remains a challenge to identify inhibitors with both excellent in vitro potency and drug-like physiochemical properties which would lead to good in vivo activities.
Keywords: protein phosphatase, protein tyrosine phosphatase 1b, ptp1b, ptp1b inhibitors, diabetes, anti-hyperglycemia, insulin resistance, obesity
Current Pharmaceutical Design
Title: Inhibition of Protein Tyrosine Phosphatase 1B as a Potential Treatment of Diabetes and Obesity
Volume: 10 Issue: 28
Author(s): Zhonghua Pei, Gang Liu, Thomas H. Lubben and Bruce G. Szczepankiewicz
Affiliation:
Keywords: protein phosphatase, protein tyrosine phosphatase 1b, ptp1b, ptp1b inhibitors, diabetes, anti-hyperglycemia, insulin resistance, obesity
Abstract: Diabetes is a prevalent disease which effects over 150 million people worldwide and there is a great medical need for new therapeutic agents to treat it. Inhibition of protein tyrosine phosphatase 1B (PTP1B) has emerged as a highly validated, attractive target for treatment of not only diabetes but also obesity. Discovery of small-molecule inhibitors has been pursued extensively in both academia and industry and a number of very potent and selective inhibitors have been identified. With X-ray crystallography, the binding interactions of several classes of inhibitors have been elucidated. This has resulted in significant progress in understanding important interactions between inhibitors and specific residues of PTP1B, which could help the design of future inhibitors. However, since the active site of PTP1B that most of these inhibitors bind to is highly hydrophilic, it remains a challenge to identify inhibitors with both excellent in vitro potency and drug-like physiochemical properties which would lead to good in vivo activities.
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Cite this article as:
Pei Zhonghua, Liu Gang, Lubben H. Thomas and Szczepankiewicz G. Bruce, Inhibition of Protein Tyrosine Phosphatase 1B as a Potential Treatment of Diabetes and Obesity, Current Pharmaceutical Design 2004; 10 (28) . https://dx.doi.org/10.2174/1381612043382954
DOI https://dx.doi.org/10.2174/1381612043382954 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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