Show simple item record

dc.contributor.authorChessum, NEA
dc.contributor.authorSharp, SY
dc.contributor.authorCaldwell, JJ
dc.contributor.authorPasqua, AE
dc.contributor.authorWilding, B
dc.contributor.authorColombano, G
dc.contributor.authorCollins, I
dc.contributor.authorOzer, B
dc.contributor.authorRichards, M
dc.contributor.authorRowlands, M
dc.contributor.authorStubbs, M
dc.contributor.authorBurke, R
dc.contributor.authorMcAndrew, PC
dc.contributor.authorClarke, PA
dc.contributor.authorWorkman, P
dc.contributor.authorCheeseman, MD
dc.contributor.authorJones, K
dc.date.accessioned2017-12-15T10:48:46Z
dc.date.issued2018-02-08
dc.identifier.citationJournal of medicinal chemistry, 2018, 61 (3), pp. 918 - 933
dc.identifier.issn0022-2623
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/971
dc.identifier.eissn1520-4804
dc.identifier.doi10.1021/acs.jmedchem.7b01406
dc.description.abstractDemonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging for poorly studied and noncatalytic proteins, as robust proximal biomarkers are rarely known. To confirm that our recently discovered chemical probe 1 (CCT251236) binds the putative transcription factor regulator pirin in living cells, we developed a heterobifunctional protein degradation probe. Focusing on linker design and physicochemical properties, we generated a highly active probe 16 (CCT367766) in only three iterations, validating our efficient strategy for degradation probe design against nonvalidated protein targets.
dc.formatPrint-Electronic
dc.format.extent918 - 933
dc.languageeng
dc.language.isoeng
dc.publisherAMER CHEMICAL SOC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line
dc.subjectCell Survival
dc.subjectProtein Conformation
dc.subjectModels, Molecular
dc.subjectProteolysis
dc.subjectPrion Proteins
dc.titleDemonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766).
dc.typeJournal Article
dcterms.dateAccepted2017-12-14
rioxxterms.versionofrecord10.1021/acs.jmedchem.7b01406
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of medicinal chemistry
pubs.issue3
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/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
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/Hit Discovery & Structural Design
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 3
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Hit Discovery & Structural Design
pubs.publication-statusPublished
pubs.volume61
pubs.embargo.termsNot known
icr.researchteamMedicinal Chemistry 2
icr.researchteamMedicinal Chemistry 3
icr.researchteamSignal Transduction & Molecular Pharmacology
icr.researchteamHit Discovery & Structural Design
dc.contributor.icrauthorChessum, Nicola
dc.contributor.icrauthorCaldwell, John
dc.contributor.icrauthorCollins, Ian
dc.contributor.icrauthorOzer, Bugra
dc.contributor.icrauthorBurke, Rosemary
dc.contributor.icrauthorClarke, Paul
dc.contributor.icrauthorWorkman, Paul
dc.contributor.icrauthorCheeseman, Matthew
dc.contributor.icrauthorJones, Keith


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0