Progress in discovery of small-molecule modulators of protein-protein interactions via fragment screening

Thomas V Magee

doi:10.1016/j.bmcl.2015.04.089

Progress in discovery of small-molecule modulators of protein-protein interactions via fragment screening

Bioorg Med Chem Lett. 2015 Jun 15;25(12):2461-8. doi: 10.1016/j.bmcl.2015.04.089. Epub 2015 May 2.

Author

Thomas V Magee¹

Affiliation

¹ Worldwide Medicinal Chemistry, Pfizer Inc, 610 Main Street, Cambridge, MA 02139, USA. Electronic address: thomas.v.magee@pfizer.com.

PMID: 25971770
DOI: 10.1016/j.bmcl.2015.04.089

Abstract

Protein-protein interactions (PPIs) present a formidable challenge to medicinal chemistry. The extended and open nature of many binding sites at protein interfaces has made it difficult to find useful chemical matter by traditional screening methods using standard screening libraries. This Digest focuses on the progress that has been made in discovering small-molecule modulators for a diverse selection of PPI targets using fragment screening and highlights the utility of this strategy in this context.

Keywords: Fragments; PPI.

Publication types

Review

MeSH terms

Apoptosis Regulatory Proteins / chemistry
Apoptosis Regulatory Proteins / metabolism
Bacterial Proteins / chemistry
Bacterial Proteins / metabolism
Binding Sites
Molecular Dynamics Simulation
Protein Interaction Domains and Motifs
Proteins / chemistry*
Proteins / metabolism
Small Molecule Libraries / chemistry*
Small Molecule Libraries / metabolism

Substances

Apoptosis Regulatory Proteins
Bacterial Proteins
Proteins
Small Molecule Libraries