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dc.contributor.authorAllen, Timothyen
dc.contributor.authorLiggi, Soniaen
dc.contributor.authorGoodman, Jonathanen
dc.contributor.authorGutsell, Sen
dc.contributor.authorRussell, PJen
dc.date.accessioned2016-11-17T15:45:59Z
dc.date.available2016-11-17T15:45:59Z
dc.date.issued2016-10-17en
dc.identifier.issn0893-228X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261198
dc.description.abstractMolecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties that allow them to exhibit this behavior, be these properties stereochemical, electronic, or otherwise. In an attempt to discover some of these chemical characteristics, we have constructed structural alert-style structure-activity relationships (SARs) to computationally predict MIEs. This work utilizes chemical informatics approaches, searching the ChEMBL database for molecules that bind to a number of pharmacologically important human toxicology targets, including G-protein coupled receptors, enzymes, ion channels, nuclear receptors, and transporters. By screening these compounds to find common 2D fragments and combining this approach with a good understanding of the literature, bespoke 2D structural alerts have been written. These SARs form the beginning of a tool for screening novel chemicals to establish the kind of interactions that they may be able to make in humans. These SARs have been run through an internal validation to test their quality, and the results of this are also discussed. MIEs have proven to be difficult to find and characterize, but we believe we have taken a key first step with this work.
dc.description.sponsorshipUnilever
dc.languageENGen
dc.language.isoenen
dc.publisherAmerican Chemical Society
dc.titleUsing Molecular Initiating Events To Generate 2D Structure-Activity Relationships for Toxicity Screeningen
dc.typeArticle
prism.endingPage1627
prism.issueIdentifier10en
prism.publicationDate2016en
prism.publicationNameChemical Research in Toxicologyen
prism.startingPage1611
prism.volume29en
dc.identifier.doi10.17863/CAM.6368
dcterms.dateAccepted2016-09-07en
rioxxterms.versionofrecord10.1021/acs.chemrestox.6b00101en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-10-17en
dc.contributor.orcidAllen, Timothy [0000-0001-7369-0901]
dc.contributor.orcidLiggi, Sonia [0000-0003-1802-357X]
dc.contributor.orcidGoodman, Jonathan [0000-0002-8693-9136]
dc.identifier.eissn1520-5010
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2016-09-07en
rioxxterms.freetoread.startdate2017-09-07


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