title: Application of NMR screening in drug discovery.
abstract: The application of NMR screening in drug discovery has recently attained heightened importance throughout the pharmaceutical industry. NMR screening can be applied at various points in a drug discovery program, ranging from very early in the program, when new targets can be screened long before an HTS enzymatic assay is developed, to later in the program, as in the case where no useful hits have been detected by HTS using biological assays. The binders determined in primary NMR screens are used to guide secondary screens, which can be either completely NMR driven or use NMR in combination with other biophysical techniques. In this review we briefly discuss the methods and techniques used in NMR screening. Then, we describe in detail the NMR screening strategies and their applications to specific targets, including successful examples from actual drug design programs at our own and other pharmaceutical companies.
authors.affiliation: Vertex Pharmaceuticals, Incorporated, 130 Waverly Street, Cambridge, MA 02139-4242, USA. jasna@vpharm.com
authors.forename: Jasna
authors.initials: J
authors.lastname: Fejzo
authors.forename: Christopher
authors.initials: C
authors.lastname: Lepre
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xie
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins