title: Efficient exploration of chemical space by fragment-based screening.
abstract: Screening methods seek to sample a vast chemical space in order to identify starting points for further chemical optimisation. Fragment based drug discovery exploits the superior sampling of chemical space that can be achieved when the molecular weight is restricted. Here we show that commercially available fragment space is still relatively poorly sampled and argue for highly sensitive screening methods to allow the detection of smaller fragments. We analyse the properties of our fragment library versus the properties of X-ray hits derived from the library. We particularly consider properties related to the degree of planarity of the fragments.
authors.affiliation: Astex Pharmaceuticals, 436 Cambridge Science Park, Milton, Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hall
authors.affiliation: Astex Pharmaceuticals, 436 Cambridge Science Park, Milton, Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Mortenson
authors.affiliation: Astex Pharmaceuticals, 436 Cambridge Science Park, Milton, Road, Cambridge CB4 0QA, United Kingdom. Electronic address: chris.murray@astx.com.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Murray
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries
keywords: 3D fragments; Fragment library; Fragment-based drug design; Properties of fragment hits; Size of chemical space