title: Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening.
abstract: Analyzing the chemical space coverage in commercial fragment screening collections revealed the overlap between bioactive medicinal chemistry substructures and rule-of-three compliant fragments is only ∼25%. We recommend including these fragments in fragment screening libraries to maximize confidence in discovering hit matter within known bioactive chemical space, while incorporation of nonoverlapping substructures could offer novel hits in screening libraries. Using principal component analysis, polar and three-dimensional substructures display a higher-than-average enrichment of bioactive compounds, indicating increasing representation of these substructures may be beneficial in fragment screening.
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research , 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
authors.forename: N Yi
authors.initials: NY
authors.lastname: Mok
authors.forename: Ruth
authors.initials: R
authors.lastname: Brenk
authors.forename: Nathan
authors.initials: N
authors.lastname: Brown
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000706:statistics & numerical data; D019295:Computational Biology; D062126:Databases, Chemical; D062313:Databases, Pharmaceutical; D055808:Drug Discovery / Q000379:methods* / Q000706:statistics & numerical data; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000706:statistics & numerical data; D008955:Models, Cardiovascular; D015394:Molecular Structure; D025341:Principal Component Analysis