dc.contributor.author | Hartung, IV | |
dc.contributor.author | Rudolph, J | |
dc.contributor.author | Mader, MM | |
dc.contributor.author | Mulder, MPC | |
dc.contributor.author | Workman, P | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-09-29T11:43:00Z | |
dc.date.available | 2023-09-29T11:43:00Z | |
dc.date.issued | 2023-07-27 | |
dc.identifier.citation | Journal of Medicinal Chemistry, 2023, 66 (14), pp. 9297 - 9312 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5997 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.eissn | 1520-4804 | |
dc.identifier.doi | 10.1021/acs.jmedchem.3c00550 | |
dc.description.abstract | Within druggable target space, new small-molecule modalities, particularly covalent inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists. Molecules with such modes of action have a large potential not only as drugs but also as chemical probes. Criteria have previously been established to describe the potency, selectivity, and properties of small-molecule probes that are qualified to enable the interrogation and validation of drug targets. These definitions have been tailored to reversibly acting modulators but fall short in their applicability to other modalities. While initial guidelines have been proposed, we delineate here a full set of criteria for the characterization of covalent, irreversible inhibitors as well as heterobifunctional degraders ("proteolysis-targeting chimeras", or PROTACs) and molecular glue degraders. We propose modified potency and selectivity criteria compared to those for reversible inhibitors. We discuss their relevance and highlight examples of suitable probe and pathfinder compounds. | |
dc.format | Print-Electronic | |
dc.format.extent | 9297 - 9312 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER CHEMICAL SOC | |
dc.relation.ispartof | Journal of Medicinal Chemistry | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Proteolysis | |
dc.subject | Ubiquitin-Protein Ligases | |
dc.title | Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-07-05 | |
dc.date.updated | 2023-09-29T11:41:19Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1021/acs.jmedchem.3c00550 | |
rioxxterms.licenseref.startdate | 2023-07-27 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37403870 | |
pubs.issue | 14 | |
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/Signal Transduction & Molecular Pharmacology | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1021/acs.jmedchem.3c00550 | |
pubs.volume | 66 | |
icr.researchteam | Signal Trans & Mol Pharma | |
dc.contributor.icrauthor | Workman, Paul | |
icr.provenance | Deposited by Mr Arek Surman on 2023-09-29. Deposit type is initial. No. of files: 1. Files: Expanding Chemical Probe Space Quality Criteria for Covalent and Degrader Probes.pdf | |