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dc.date.accessioned2018-06-28T09:25:15Z
dc.date.issued2009en_US
dc.identifierhttp://publications.icr.ac.uk/7750/en_US
dc.identifier.citationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (3), pp. 1128 - 1134en_US
dc.identifier.issn0223-5234en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1960
dc.description.abstractA database of 1070 marketed drug compounds was compiled and analyzed in order to assess the occurrence of moieties described in the literature as "undesirable" for high-throughput screening compound libraries due to their ability to perturb assay formats. The study revealed a total of 277 compounds, 26% of the database, contained at least one of the moieties. As some of the drug compounds contained more than one "undesirable" moiety, the total number was 352. Electrophilic reactive groups, particularly aliphatic esters, were the most abundant type with 55% of the total. Half of the drug compounds incorporating the "undesirable" moieties were synthetic organic molecules. These findings suggest that "undesirable" moieties do not pose a major hindrance during clinical trials, the most expensive phase of drug development. In addition, their early elimination in the preclinical. stage excludes large regions of known drug space due to the reliance on biochemical and cell-based assays. In general, it can be concluded that compounds with "undesirable" moieties should not simply be eliminated from compound screening libraries but rather be flagged as potentially problematic. A possible solution is to segregate the compounds containing suspect moieties and screen them when deemed appropriate. (C) 2008 Elsevier Masson SAS. All rights reserved.en_US
dc.format.extent1128 - 1134en_US
dc.subjectDrug chemical space Toxic and promiscuous chemical moieties Drug- and lead-like chemical space and drug discovery PROMISCUOUS INHIBITORS PROPERTY PROFILES ORAL-DRUGS DISCOVERY PERMEABILITY SOLUBILITY MECHANISM HTS DNAen_US
dc.titleInvestigation of the incidence of "undesirable" molecular moieties for high-throughput screening compound libraries in marketed drug compoundsen_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2009en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfEUROPEAN JOURNAL OF MEDICINAL CHEMISTRYen_US
pubs.issue3en_US
pubs.notesnone A database of 1070 marketed drug compounds was compiled and analyzed in order to assess the occurrence of moieties described in the literature as "undesirable" for high-throughput screening compound libraries due to their ability to perturb assay formats. The study revealed a total of 277 compounds, 26% of the database, contained at least one of the moieties. As some of the drug compounds contained more than one "undesirable" moiety, the total number was 352. Electrophilic reactive groups, particularly aliphatic esters, were the most abundant type with 55% of the total. Half of the drug compounds incorporating the "undesirable" moieties were synthetic organic molecules. These findings suggest that "undesirable" moieties do not pose a major hindrance during clinical trials, the most expensive phase of drug development. In addition, their early elimination in the preclinical. stage excludes large regions of known drug space due to the reliance on biochemical and cell-based assays. In general, it can be concluded that compounds with "undesirable" moieties should not simply be eliminated from compound screening libraries but rather be flagged as potentially problematic. A possible solution is to segregate the compounds containing suspect moieties and screen them when deemed appropriate. (C) 2008 Elsevier Masson SAS. All rights reserved.en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.volume44en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorAxerio-Cilies, Peteren_US
dc.contributor.icrauthorCastaneda, Ivanen_US


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