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dc.contributor.authorBery, N
dc.contributor.authorBataille, CJR
dc.contributor.authorRussell, A
dc.contributor.authorHayes, A
dc.contributor.authorRaynaud, F
dc.contributor.authorMilhas, S
dc.contributor.authorAnand, S
dc.contributor.authorTulmin, H
dc.contributor.authorMiller, A
dc.contributor.authorRabbitts, TH
dc.date.accessioned2021-05-19T14:00:06Z
dc.date.available2021-05-19T14:00:06Z
dc.date.issued2021-04-09
dc.identifier.citationScience advances, 2021, 7 (15)
dc.identifier.issn2375-2548
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4562
dc.identifier.eissn2375-2548
dc.identifier.eissn2375-2548en_US
dc.identifier.doi10.1126/sciadv.abg1950
dc.identifier.doi10.1126/sciadv.abg1950en_US
dc.description.abstractIntracellular antibodies are tools that can be used directly for target validation by interfering with properties like protein-protein interactions. An alternative use of intracellular antibodies in drug discovery is developing small-molecule surrogates using antibody-derived (Abd) technology. We previously used this strategy with an in vitro competitive surface plasmon resonance method that relied on high-affinity antibody fragments to obtain RAS-binding compounds. We now describe a novel implementation of the Abd method with a cell-based intracellular antibody-guided screening method that we have applied to the chromosomal translocation protein LMO2. We have identified a chemical series of anti-LMO2 Abd compounds that bind at the same LMO2 location as the inhibitory anti-LMO2 intracellular antibody combining site. Intracellular antibodies could therefore be used in cell-based screens to identify chemical surrogates of their binding sites and potentially be applied to any challenging proteins, such as transcription factors that have been considered undruggable.
dc.formatElectronic-Print
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleA cell-based screening method using an intracellular antibody for discovering small molecules targeting the translocation protein LMO2.
dc.typeJournal Article
dcterms.dateAccepted2021-02-19
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1126/sciadv.abg1950
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-04-09
rioxxterms.licenseref.startdate2021-04-09en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfScience advances
pubs.issue15
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Chromosomal Translocations and Intracellular Antibody Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Chromosomal Translocations and Intracellular Antibody Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Clinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
pubs.publication-statusPublished
pubs.volume7en_US
pubs.embargo.termsNot known
icr.researchteamChromosomal Translocations and Intracellular Antibody Therapeutics
icr.researchteamClinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)
icr.researchteamChromosomal Translocations and Intracellular Antibody Therapeuticsen_US
icr.researchteamClinical Pharmacology & Trials (including Drug Metabolism & Pharmacokinetics Group)en_US
dc.contributor.icrauthorRabbitts, Terenceen
dc.contributor.icrauthorRaynaud, Florenceen


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