title: Modulators of protein-protein interactions: novel approaches in targeting protein kinases and other pharmaceutically relevant biomolecules.
abstract: In recent years the development of small organic molecules modulating protein-protein interactions (P-PIs) has drawn major attention in both academic and industrial research. Despite the appreciable progress being made, targeting such extensive interaction areas with comparatively small, drug-like agents has proven to be an ambitious objective. This review highlights the reasons rendering this task highly challenging and provides an overview on the latest developments in rational design approaches for P-PI modulators. The significance, scope and limitations of computational methods in this particular field of research are analyzed. Recent successfully identified and designed P-PI modulators are discussed. Thereby, particular focus is taken on small organic molecules disrupting protein-protein interfaces of protein kinases.
authors.affiliation: Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Rechfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Gruber
authors.forename: Johann
authors.initials: J
authors.lastname: Hofmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
mesh_terms: D019295:Computational Biology; D015195:Drug Design; D006801:Humans; D056004:Molecular Dynamics Simulation; D058990:Molecular Targeted Therapy; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D009930:Organic Chemicals; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases