dc.contributor.author | Chessum, NEA | |
dc.contributor.author | Sharp, SY | |
dc.contributor.author | Caldwell, JJ | |
dc.contributor.author | Pasqua, AE | |
dc.contributor.author | Wilding, B | |
dc.contributor.author | Colombano, G | |
dc.contributor.author | Collins, I | |
dc.contributor.author | Ozer, B | |
dc.contributor.author | Richards, M | |
dc.contributor.author | Rowlands, M | |
dc.contributor.author | Stubbs, M | |
dc.contributor.author | Burke, R | |
dc.contributor.author | McAndrew, PC | |
dc.contributor.author | Clarke, PA | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Cheeseman, MD | |
dc.contributor.author | Jones, K | |
dc.date.accessioned | 2017-12-15T10:48:46Z | |
dc.date.issued | 2018-02-08 | |
dc.identifier.citation | Journal of medicinal chemistry, 2018, 61 (3), pp. 918 - 933 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/971 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.7b01406 | |
dc.description.abstract | Demonstrating 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.format | Print-Electronic | |
dc.format.extent | 918 - 933 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line | |
dc.subject | Cell Survival | |
dc.subject | Protein Conformation | |
dc.subject | Models, Molecular | |
dc.subject | Proteolysis | |
dc.subject | Prion Proteins | |
dc.title | Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766). | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-12-14 | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.7b01406 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of medicinal chemistry | |
pubs.issue | 3 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 61 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Medicinal Chemistry 2 | |
icr.researchteam | Medicinal Chemistry 3 | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
icr.researchteam | Hit Discovery & Structural Design | |
dc.contributor.icrauthor | Chessum, Nicola | |
dc.contributor.icrauthor | Caldwell, John | |
dc.contributor.icrauthor | Collins, Ian | |
dc.contributor.icrauthor | Ozer, Bugra | |
dc.contributor.icrauthor | Burke, Rosemary | |
dc.contributor.icrauthor | Clarke, Paul | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Cheeseman, Matthew | |
dc.contributor.icrauthor | Jones, Keith | |