title: Structure-based screening and design in drug discovery.
abstract: Structure-based screening represents an integrated approach for the identification and optimization of hits by the combined use of nuclear magnetic resonance (NMR) spectroscopy, homology modeling and X-ray crystallography. A general feature of the methodology is the introduction of structure-based methods (NMR, modeling and X-ray) early in the drug discovery process to optimize hits in terms of their affinities and specificities. This approach promises to deliver leads with improved physicochemical properties as compared with leads generated from a traditional HTS program. This review presents examples of structure-based screening from published and in-house drug discovery projects.
authors.affiliation: Biovitrum AB, Department of Structural Chemistry, N62:5, SE-112 76, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: van Dongen
authors.forename: Johan
authors.initials: J
authors.lastname: Weigelt
authors.forename: Jonas
authors.initials: J
authors.lastname: Uppenberg
authors.forename: Johan
authors.initials: J
authors.lastname: Schultz
authors.forename: Mats
authors.initials: M
authors.lastname: Wikström
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations