title: From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery.
abstract: Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design.
authors.affiliation: Laboratorio de Quimica Medicinal e Computacional, Centro de Pesquisa e Inovacao em Biodiversidade e Farmacos, Instituto de Física de Sao Carlos, Universidade de Sao Paulo, Av. Joao Dagnone 1100, 13563-120, Sao Carlos, SP, Brazil.
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: Laboratorio de Quimica Medicinal e Computacional, Centro de Pesquisa e Inovacao em Biodiversidade e Farmacos, Instituto de Física de Sao Carlos, Universidade de Sao Paulo, Av. Joao Dagnone 1100, 13563-120, Sao Carlos, SP, Brazil.
authors.forename: Adriano D
authors.initials: AD
authors.lastname: Andricopulo
mesh_terms: D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery; D015394:Molecular Structure; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries
keywords: FBDD; Lead optimization; NMR; SBDD; Screening; X-ray crystallography