title: Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.
abstract: Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Scott
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.|Vertex Pharmaceuticals Incorporated, 86-88 Jubilee Avenue, Milton Park, Abingdon OX14 4RW, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Bayly
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Abell
authors.affiliation: Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0AH, UK.
authors.forename: John
authors.initials: J
authors.lastname: Skidmore
mesh_terms: D000818:Animals; D019295:Computational Biology; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000187:drug effects*; D054852:Small Molecule Libraries
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries