0 86

Cited 0 times in

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

DC FieldValueLanguage
dc.contributor.author센굽타산딥-
dc.contributor.author심태보-
dc.contributor.author조한나-
dc.date.accessioned2020-12-11T08:10:53Z-
dc.date.available2020-12-11T08:10:53Z-
dc.date.issued2020-12-
dc.identifier.issn0092-8674-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/180803-
dc.description.abstractTargeted protein degradation (TPD) refers to the use of small molecules to induce ubiquitin-dependent degradation of proteins. TPD is of interest in drug development, as it can address previously inaccessible targets. However, degrader discovery and optimization remains an inefficient process due to a lack of understanding of the relative importance of the key molecular events required to induce target degradation. Here, we use chemo-proteomics to annotate the degradable kinome. Our expansive dataset provides chemical leads for ∼200 kinases and demonstrates that the current practice of starting from the highest potency binder is an ineffective method for discovering active compounds. We develop multitargeted degraders to answer fundamental questions about the ubiquitin proteasome system, uncovering that kinase degradation is p97 dependent. This work will not only fuel kinase degrader discovery, but also provides a blueprint for evaluating targeted degradation across entire gene families to accelerate understanding of TPD beyond the kinome.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherCell Press-
dc.relation.isPartOfCELL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleMapping the Degradable Kinome Provides a Resource for Expedited Degrader Development-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorKatherine A Donovan-
dc.contributor.googleauthorFleur M Ferguson-
dc.contributor.googleauthorJonathan W Bushman-
dc.contributor.googleauthorNicholas A Eleuteri-
dc.contributor.googleauthorDebabrata Bhunia-
dc.contributor.googleauthorSeongShick Ryu-
dc.contributor.googleauthorLi Tan-
dc.contributor.googleauthorKun Shi-
dc.contributor.googleauthorHong Yue-
dc.contributor.googleauthorXiaoxi Liu-
dc.contributor.googleauthorDennis Dobrovolsky-
dc.contributor.googleauthorBaishan Jiang-
dc.contributor.googleauthorJinhua Wang-
dc.contributor.googleauthorMingfeng Hao-
dc.contributor.googleauthorInchul You-
dc.contributor.googleauthorMingxing Teng-
dc.contributor.googleauthorYanke Liang-
dc.contributor.googleauthorJohn Hatcher-
dc.contributor.googleauthorZhengnian Li-
dc.contributor.googleauthorTheresa D Manz-
dc.contributor.googleauthorBrian Groendyke-
dc.contributor.googleauthorWanyi Hu-
dc.contributor.googleauthorYunju Nam-
dc.contributor.googleauthorSandip Sengupta-
dc.contributor.googleauthorHanna Cho-
dc.contributor.googleauthorInjae Shin-
dc.contributor.googleauthorMichael P Agius-
dc.contributor.googleauthorIrene M Ghobrial-
dc.contributor.googleauthorMichelle W Ma-
dc.contributor.googleauthorJianwei Che-
dc.contributor.googleauthorSara J Buhrlage-
dc.contributor.googleauthorTaebo Sim-
dc.contributor.googleauthorNathanael S Gray-
dc.contributor.googleauthorEric S Fischer-
dc.identifier.doi10.1016/j.cell.2020.10.038-
dc.contributor.localIdA05988-
dc.contributor.localIdA05926-
dc.contributor.localIdA05926-
dc.contributor.localIdA05989-
dc.contributor.localIdA05989-
dc.relation.journalcodeJ00472-
dc.identifier.eissn1097-4172-
dc.identifier.pmid33275901-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0092867420314458?-
dc.subject.keywordE3 ligase-
dc.subject.keywordIMiD-
dc.subject.keywordPROTAC-
dc.subject.keyworddegrader-
dc.subject.keywordkinase-
dc.subject.keywordtargeted degradation-
dc.subject.keywordubiquitin-
dc.subject.keywordubiquitin proteasome system-
dc.contributor.alternativeNameSengupta, Sandip-
dc.contributor.affiliatedAuthor센굽타산딥-
dc.contributor.affiliatedAuthor심태보-
dc.contributor.affiliatedAuthor심태보-
dc.contributor.affiliatedAuthor조한나-
dc.contributor.affiliatedAuthor조한나-
dc.citation.volume183-
dc.citation.startPage1-
dc.citation.endPage18-
dc.identifier.bibliographicCitationCELL, Vol.183 : 1-18, 2020-12-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.