Structure-based screening and design in drug discovery.
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.
van Dongen
Maria
M
Biovitrum AB, Department of Structural Chemistry, N62:5, SE-112 76, Stockholm, Sweden.
Weigelt
Johan
J
Uppenberg
Jonas
J
Schultz
Johan
J
Wikström
Mats
M
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
D008024:Ligands; D004364:Pharmaceutical Preparations