Mutant-Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug-Resistant Mutations
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jang, Jaebong | - |
dc.contributor.author | To, Ciric | - |
dc.contributor.author | De Clercq, Dries J. H. | - |
dc.contributor.author | Park, Eunyoung | - |
dc.contributor.author | Ponthier, Charles M. | - |
dc.contributor.author | Shin, Bo Hee | - |
dc.contributor.author | Mushajiang, Mierzhati | - |
dc.contributor.author | Nowak, Radoslaw P. | - |
dc.contributor.author | Fischer, Eric S. | - |
dc.contributor.author | Eck, Michael J. | - |
dc.contributor.author | Janne, Pasi A. | - |
dc.contributor.author | Gray, Nathanael S. | - |
dc.date.accessioned | 2021-08-30T16:50:39Z | - |
dc.date.available | 2021-08-30T16:50:39Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-08-17 | - |
dc.identifier.issn | 1433-7851 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/53755 | - |
dc.description.abstract | Targeting epidermal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic strategy to overcome drug-resistant EGFR mutations that emerge within the ATP binding site. Here, we develop an allosteric EGFR degrader, DDC-01-163, which can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected. DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. When combined with an ATP-site EGFR inhibitor, osimertinib, the anti-proliferative activity of DDC-01-163 against L858R/T790M EGFR-Ba/F3 cells is enhanced. Collectively, DDC-01-163 is a promising allosteric EGFR degrader with selective activity against various clinically relevant EGFR mutants as a single agent and when combined with an ATP-site inhibitor. Our data suggests that targeted protein degradation is a promising drug development approach for mutant EGFR. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | WILEY-V C H VERLAG GMBH | - |
dc.subject | GROWTH-FACTOR-RECEPTOR | - |
dc.subject | CELL LUNG-CANCER | - |
dc.subject | ACQUIRED-RESISTANCE | - |
dc.subject | PROTEIN-DEGRADATION | - |
dc.subject | AZD9291 | - |
dc.subject | INHIBITION | - |
dc.subject | POTENT | - |
dc.subject | OSIMERTINIB | - |
dc.subject | DISCOVERY | - |
dc.subject | FREQUENCY | - |
dc.title | Mutant-Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug-Resistant Mutations | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jang, Jaebong | - |
dc.identifier.doi | 10.1002/anie.202003500 | - |
dc.identifier.scopusid | 2-s2.0-85087676831 | - |
dc.identifier.wosid | 000546374600001 | - |
dc.identifier.bibliographicCitation | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v.59, no.34, pp.14481 - 14489 | - |
dc.relation.isPartOf | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | - |
dc.citation.title | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | - |
dc.citation.volume | 59 | - |
dc.citation.number | 34 | - |
dc.citation.startPage | 14481 | - |
dc.citation.endPage | 14489 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | GROWTH-FACTOR-RECEPTOR | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | PROTEIN-DEGRADATION | - |
dc.subject.keywordPlus | AZD9291 | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | POTENT | - |
dc.subject.keywordPlus | OSIMERTINIB | - |
dc.subject.keywordPlus | DISCOVERY | - |
dc.subject.keywordPlus | FREQUENCY | - |
dc.subject.keywordAuthor | allosteric | - |
dc.subject.keywordAuthor | combination treatment | - |
dc.subject.keywordAuthor | degrader | - |
dc.subject.keywordAuthor | drug-resistant mutation | - |
dc.subject.keywordAuthor | EGFR | - |
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