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Hot Spot-Based Design of Small-Molecule Inhibitors for Protein-Protein Interactions

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Targeting Protein-Protein Interactions by Small Molecules

Abstract

Protein-protein interactions (PPIs) are important targets for the development of chemical probes and therapeutic agents. From the initial discovery of the existence of hot spots at PPI interfaces, it has been proposed that hot spots might provide the key for developing small-molecule PPI inhibitors. However, there has been no review on the ways in which the knowledge of hot spots can be used to achieve inhibitor design, nor critical examination of successful examples. This chapter discusses the characteristics of hot spots and the identification of druggable hot spot pockets. An analysis of four examples of hot spot-based design reveals the importance of this strategy in discovering potent and selective PPI inhibitors. A general procedure for hot spot-based design of PPI inhibitors is outlined.

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Authors and Affiliations

  1. Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC room 4047, Tampa, FL, 33612-9416, USA

    Haitao Ji

  2. Departments of Oncologic Sciences and Chemistry, University of South Florida, Tampa, FL, USA

    Haitao Ji

Authors
  1. Haitao Ji
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Correspondence to Haitao Ji .

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  1. School of Pharmacy, Second Military Medical University, Shanghai, China

    Chunquan Sheng

  2. College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

    Gunda I. Georg

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Ji, H. (2018). Hot Spot-Based Design of Small-Molecule Inhibitors for Protein-Protein Interactions. In: Sheng, C., Georg, G. (eds) Targeting Protein-Protein Interactions by Small Molecules. Springer, Singapore. https://doi.org/10.1007/978-981-13-0773-7_3

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