Small molecular weight protein-protein interaction antagonists: an insurmountable challenge?
Several years ago small molecular weight protein-protein interaction (PPI) antagonists were considered as the Mount Everest in drug discovery and generally regarded as too difficult to be targeted. However, recent industrial and academic research has produced a great number of new antagonists of diverse PPIs. This review structurally analyses small molecular weight PPI antagonists and their particular targets as well as tools to discover such compounds. Besides general discussions there will be a focus on the PPI p53/mdm2.
Dömling
Alexander
A
Department of Pharmaceutical Sciences and Chemistry, University of Pittsburgh, PA, USA. asd30@pitt.edu
D000818:Animals; D006801:Humans; D008970:Molecular Weight; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism
D011506:Proteins; D054852:Small Molecule Libraries; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2