Please use this identifier to cite or link to this item: https://doi.org/10.1089/ars.2013.5710
Title: Bidentate inhibitors of protein tyrosine phosphatases
Authors: Low, J.-L.
Chai, C.L.L. 
Yao, S.Q. 
Issue Date: 10-May-2014
Citation: Low, J.-L., Chai, C.L.L., Yao, S.Q. (2014-05-10). Bidentate inhibitors of protein tyrosine phosphatases. Antioxidants and Redox Signaling 20 (14) : 2225-2250. ScholarBank@NUS Repository. https://doi.org/10.1089/ars.2013.5710
Abstract: Significance: Protein tyrosine phosphatases (PTPs) are important enzymes that are involved in the regulation of cellular signaling. Evidence accumulated over the years has indicated that PTPs present exciting opportunities for drug discovery against diseases such as diabetes, cancer, autoimmune diseases, and tuberculosis. However, the highly conserved and partially positive charge of the catalytic sites of PTPs is a major challenge in the development of potent and highly selective PTP inhibitors. Recent Advances: Here, we examine the strategy of developing bidentate inhibitors for selective inhibition of PTPs. Bidentate inhibitors are small-molecular-weight compounds with the ability to bind to both the active site and a non-conserved secondary phosphate binding site. This secondary phosphate binding site was initially discovered in protein tyrosine phosphatase 1B (PTP1B), and, hence, most of the bidentate inhibitors reported in this review are PTP1B inhibitors. Critical Issues: Although bidentate inhibition is a good strategy for developing potent and selective inhibitors, the cell membrane permeability and pharmacokinetic properties of the inhibitors are also important for successful drug development. In this review, we will also summarize the various efforts made toward the development of phosphotyrosine (pTyr) mimetics for increasing cellular permeability. Future Directions: Even though the secondary phosphate binding site was initially found in PTP1B, structural data have shown that a secondary binding site can also be found in other PTPs, albeit with varying degrees of accessibility. Along with improvements in pTyr mimetics, we believe that the future will see an increase in the number of orally bioavailable bidentate inhibitors against the various classes of PTPs. Antioxid. Redox Signal. 20, 2225-2250. © 2014 Mary Ann Liebert, Inc.
Source Title: Antioxidants and Redox Signaling
URI: http://scholarbank.nus.edu.sg/handle/10635/95547
ISSN: 15577716
DOI: 10.1089/ars.2013.5710
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