title: Transforming fragments into candidates: small becomes big in medicinal chemistry.
abstract: Fragment-based drug discovery (FBDD) represents a logical and efficient approach to lead discovery and optimisation. It can draw on structural, biophysical and biochemical data, incorporating a wide range of inputs, from precise mode-of-binding information on specific fragments to wider ranging pharmacophoric screening surveys using traditional HTS approaches. It is truly an enabling technology for the imaginative medicinal chemist. In this review, we analyse a representative set of 23 published FBDD studies that describe how low molecular weight fragments are being identified and efficiently transformed into higher molecular weight drug candidates. FBDD is now becoming warmly endorsed by industry as well as academia and the focus on small interacting molecules is making a big scientific impact.
authors.affiliation: Leiden/Amsterdam Center for Drug Research (LACDR), Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: Gerdien E
authors.initials: GE
authors.lastname: de Kloe
authors.forename: David
authors.initials: D
authors.lastname: Bailey
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
authors.forename: Iwan J P
authors.initials: IJ
authors.lastname: de Esch
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends*; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D006801:Humans; D010446:Peptide Fragments / Q000138:chemical synthesis; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis
chemical_list: D010446:Peptide Fragments; D004364:Pharmaceutical Preparations