title: Stabilization of protein-protein interactions by small molecules.
abstract: Protein-protein interactions (PPIs) are implicated in every disease and mastering the ability to influence PPIs with small molecules would considerably enlarge the druggable genome. Whereas inhibition of PPIs has repeatedly been shown to work successfully, targeted stabilization of PPIs is underrepresented in the literature. This is all the more surprising because natural products like FK506, rapamycin, brefeldin, forskolin and fusicoccin confer their physiological activity by stabilizing specific PPIs. However, recently a number of very interesting synthetic molecules have been reported from drug discovery projects that indeed achieve their desired activities by stabilizing either homo- or hetero-oligomeric complexes of their target proteins.
authors.affiliation: Medicinal Chemistry, Taros Chemicals, Emil-Figge-Str. 76a, 44227 Dortmund, Germany.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giordanetto
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Schäfer
authors.affiliation: Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Technische Universiteit Eindhoven, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands. Electronic address: c.ottmann@tue.nl.
authors.forename: Christian
authors.initials: C
authors.lastname: Ottmann
mesh_terms: D055808:Drug Discovery; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D055550:Protein Stability / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins