title: Oncogenic protein interfaces: small molecules, big challenges.
abstract: Historically, targeting protein-protein interactions with small molecules was not thought possible because the corresponding interfaces were considered mostly flat and featureless and therefore 'undruggable'. Instead, such interactions were targeted with larger molecules, such as peptides and antibodies. However, the past decade has seen encouraging breakthroughs through the refinement of existing techniques and the development of new ones, together with the identification and exploitation of unexpected aspects of protein-protein interaction surfaces. In this Review, we describe some of the latest techniques to discover modulators of protein-protein interactions and how current drug discovery approaches have been adapted to successfully target these interfaces.
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Nero
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Morton
authors.affiliation: Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Holien
authors.affiliation: 1] Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. [2] Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
authors.forename: Jerome
authors.initials: J
authors.lastname: Wielens
authors.affiliation: 1] Australian Cancer Research Foundation Rational Drug Discovery Centre and Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. [2] Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015513:Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D015513:Oncogene Proteins