title: Chemical and structural lessons from recent successes in protein-protein interaction inhibition (2P2I).
abstract: Worldwide research efforts have driven recent pharmaceutical successes, and consequently, the emerging role of Protein-Protein Interactions (PPIs) as drug targets has finally been widely embraced by the scientific community. Inhibitors of these Protein-Protein Interactions (2P2Is or i-PPIs) are likely to represent the next generation of highly innovative drugs that will reach the market over the next decade. This review describes up-to-date knowledge on this particular chemical space, with a specific emphasis on a subset of this ensemble. We also address current structural knowledge regarding both protein-protein and protein-inhibitor complexes, that is, the 2P2I database. Finally, ligand efficiency analyses permit us to relate potency to size and polarity and to discuss the need to co-develop nanoparticle drug delivery systems.
authors.affiliation: Interactions et Modulateurs de Réponses (UPR3243), Centre National de la Recherche Scientifique (CNRS) & Université de Provence, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Morelli
authors.forename: Raphaël
authors.initials: R
authors.lastname: Bourgeas
authors.forename: Philippe
authors.initials: P
authors.lastname: Roche
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D008024:Ligands; D011506:Proteins