Small-Molecule Inhibitors of Protein-Protein Interactions: How to Mimic a Protein Partner

David      C. Fry

doi:10.2174/138161212802651634

Abstract

This systematic review describes successful examples of small-molecule inhibitors of protein-protein interactions, and compares their binding strategies to those employed by the natural protein partners. It extends and updates an earlier survey of this type (Fry DC, Curr Prot Pep Sci 2008; 9: 240-7). From analysis of these systems, common themes and lessons are presented that may assist future drug discovery efforts involving targets in this class. One encouraging finding is that a wide scope appears to be allowed at these sites in terms of binding strategies and chemotypes, which suggests that the outlook for finding small-molecule protein-protein inhibitors is favorable.

Keywords: Protein-protein inhibitor, protein-protein interaction, drug discovery, MDM2, Nutlin, targets, binding strategies, chemotypes, p53, conformation.

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Current Pharmaceutical Design

Title:Small-Molecule Inhibitors of Protein-Protein Interactions: How to Mimic a Protein Partner

Volume: 18 Issue: 30

Author(s): David C. Fry

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Keywords: Protein-protein inhibitor, protein-protein interaction, drug discovery, MDM2, Nutlin, targets, binding strategies, chemotypes, p53, conformation.

Abstract: This systematic review describes successful examples of small-molecule inhibitors of protein-protein interactions, and compares their binding strategies to those employed by the natural protein partners. It extends and updates an earlier survey of this type (Fry DC, Curr Prot Pep Sci 2008; 9: 240-7). From analysis of these systems, common themes and lessons are presented that may assist future drug discovery efforts involving targets in this class. One encouraging finding is that a wide scope appears to be allowed at these sites in terms of binding strategies and chemotypes, which suggests that the outlook for finding small-molecule protein-protein inhibitors is favorable.

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Cite this article as:

C. Fry David, Small-Molecule Inhibitors of Protein-Protein Interactions: How to Mimic a Protein Partner, Current Pharmaceutical Design 2012; 18 (30) . https://dx.doi.org/10.2174/138161212802651634

DOI https://dx.doi.org/10.2174/138161212802651634	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286

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