6533b7d2fe1ef96bd125f818
RESEARCH PRODUCT
Increasing the Coverage of Medicinal Chemistry-Relevant Space in Commercial Fragments Screening
Nathan J. BrownN. Yi MokN. Yi MokRuth BrenkRuth Brenksubject
Databases PharmaceuticalChemistry PharmaceuticalGeneral Chemical EngineeringDrug Evaluation PreclinicalCompound managementLibrary and Information Sciences01 natural sciencesMedicinal chemistryArticle03 medical and health sciencesDrug Discovery030304 developmental biologyPrincipal Component Analysis0303 health sciencesMolecular StructureDrug discoveryChemistryModels CardiovascularComputational BiologyGeneral ChemistryCombinatorial chemistryChemical space0104 chemical sciencesComputer Science Applications010404 medicinal & biomolecular chemistryDatabases Chemicaldescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-09 | Journal of Chemical Information and Modeling |