title: Protein-protein interaction inhibitors: advances in anticancer drug design.
abstract: BACKGROUND
  Pocket-based drug design has contributed to major scientific breakthroughs in pharmaceutical research and development (R&D). The integrated use of experimental and computational methods, primarily during the early phases of drug discovery, has enabled the development of highly potent and selective small-molecule ligands. In this scenario, the targeting of protein-protein interactions (PPIs) has emerged as an attractive strategy for designing innovative drugs for highly complex diseases, such as cancer.
  
  
  METHODS
  This article focuses on the use of experimental and computational approaches with a diversity of PPI classes and discusses the relevant advances in the field, primarily for oncological applications. Analyses of the target binding pockets and medicinal chemistry approaches used to develop promising PPI inhibitors are provided, with an emphasis on data reported over the past 2 years.
  
  
  CONCLUSIONS
  PPI drug discovery is a challenging field that depends completely on accurate structural data. The integration of molecular docking, nuclear magnetic resonance and X-ray crystallography is a cornerstone for the current development of effective PPI inhibitors. Although this field has not reached its peak, several compounds have entered clinical trials over the past few years, providing promising perspectives for novel therapies for highly prevalent and life-threatening conditions.
authors.affiliation: a Laboratório de Química Medicinal e Computacional, Centro de Pesquisa e Inovação em Biodiversidade e Fármacos , Instituto de Física de São Carlos, Universidade de São Paulo , São Carlos , Brazil.
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: a Laboratório de Química Medicinal e Computacional, Centro de Pesquisa e Inovação em Biodiversidade e Fármacos , Instituto de Física de São Carlos, Universidade de São Paulo , São Carlos , Brazil.
authors.forename: Glaucius
authors.initials: G
authors.lastname: Oliva
authors.affiliation: a Laboratório de Química Medicinal e Computacional, Centro de Pesquisa e Inovação em Biodiversidade e Fármacos , Instituto de Física de São Carlos, Universidade de São Paulo , São Carlos , Brazil.
authors.forename: Adriano D
authors.initials: AD
authors.lastname: Andricopulo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D011506:Proteins
keywords: Structure-based drug design; X-ray crystallography; cancer; hot spots; molecular docking; protein-protein interactions