title: Learning from our mistakes: the 'unknown knowns' in fragment screening.
abstract: In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection methods are pushed to their limits, leading to a variety of artifacts, false positives, and false negatives that too often go unrecognized. This Digest discusses some of these problems and offers suggestions to avoid them. Although the primary focus is on FBLD, many of the lessons also apply to more established approaches such as high-throughput screening.
authors.affiliation: Vernalis Ltd., Granta Park, Great Abington, Cambridge CB21 6GB, UK. b.davis@vernalis.com
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Davis
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Erlanson
mesh_terms: D055808:Drug Discovery; D057166:High-Throughput Screening Assays / Q000379:methods; D007858:Learning; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D054852:Small Molecule Libraries