title: Performance of Dark Chemical Matter in High Throughput Screening.
abstract: A statistical analysis of 203 high-throughput screens was conducted studying the propensity of small molecules in the Boehringer Ingelheim screening deck to show biological activity after having tested as inactive previously in a growing number of screening assays. Dark chemical matter (DCM) compounds, which have been tested and found to be inactive in 50 or more assays, exhibit hit rates that are comparable to those of compounds tested in much fewer assays. Only compounds tested as inactive in 125 or more assays started showing a hit rate deterioration of up to 40% compared to compounds tested in less than 25 assays. The observed large number of DCM compounds in the BI screening deck is found to be in line with the expected fraction of DCM calculated based on a probability analysis. The analysis suggests not only that DCM compounds have the chance to occasionally provide valuable hits associated with higher selectivity as recently shown by Novartis ( Nat. Chem. Biol. 2015 , 11 , 958 ) but that there is little compelling reason to exclude DCM compounds from screening decks in favor of previously untested or less tested compounds.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc. , 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Ingo
authors.initials: I
authors.lastname: Muegge
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc. , 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D057166:High-Throughput Screening Assays; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries