2. Academic Validation
  3. Hot spot-based design of small-molecule inhibitors for protein-protein interactions

Hot spot-based design of small-molecule inhibitors for protein-protein interactions

  • Bioorg Med Chem Lett. 2014 Jun 1;24(11):2546-54. doi: 10.1016/j.bmcl.2014.03.095.
Wenxing Guo 1,  John A Wisniewski 1,  Haitao Ji 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Center for Cell and Genome Science, University of Utah, 315 South 1400 East, Salt Lake City, UT 84112-0850, USA.
  • 2 Department of Chemistry, Center for Cell and Genome Science, University of Utah, 315 South 1400 East, Salt Lake City, UT 84112-0850, USA. Electronic address: [email protected].
PMID: 24751445 DOI: 10.1016/j.bmcl.2014.03.095
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 Digest 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.

Keywords

Hot spots; Inhibitor; Protein–protein interactions; Rational design; Selectivity.

Figures
Products
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    Description
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  • HY-122649
    β-catenin/Tcf PPI Inhibitor