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

  • Haitao Ji


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.


Protein-protein interactions Inhibitor Hot spots Rational design Protruding hot spots Hot spot pockets 


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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Drug Discovery DepartmentH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Departments of Oncologic Sciences and ChemistryUniversity of South FloridaTampaUSA

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