Protein-protein interactions as drug targets.
Modulation of protein-protein interactions (PPIs) is becoming increasingly important in drug discovery and chemical biology. While a few years ago this 'target class' was deemed to be largely undruggable an impressing number of publications and success stories now show that targeting PPIs with small, drug-like molecules indeed is a feasible approach. Here, we summarize the current state of small-molecule inhibition and stabilization of PPIs and review the active molecules from a structural and medicinal chemistry angle, especially focusing on the key examples of iNOS, LFA-1 and 14-3-3.
Lead Discovery Center GmbH, 44227 Dortmund, Germany.
Malgorzata
M
Skwarczynska
Laboratory of Chemical Biology & Institute of Complex Molecular Systems, Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands.|Department of Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117 Essen, Germany.
Christian
C
Ottmann
D048948:14-3-3 Proteins / Q000378:metabolism*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D060066:Protein Interaction Maps / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
D048948:14-3-3 Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D054852:Small Molecule Libraries; D052247:Nitric Oxide Synthase Type II