Pharmacological targeting of the pseudokinase Her3
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Xie, Ting | - |
dc.contributor.author | Lim, Sang Min | - |
dc.contributor.author | Westover, Kenneth D. | - |
dc.contributor.author | Dodge, Michael E. | - |
dc.contributor.author | Ercan, Dalia | - |
dc.contributor.author | Ficarro, Scott B. | - |
dc.contributor.author | Udayakumar, Durga | - |
dc.contributor.author | Gurbani, Deepak | - |
dc.contributor.author | Tae, Hyun Seop | - |
dc.contributor.author | Riddle, Steven M. | - |
dc.contributor.author | Sim, Taebo | - |
dc.contributor.author | Marto, Jarrod A. | - |
dc.contributor.author | Jaenne, Pasi A. | - |
dc.contributor.author | Crews, Craig M. | - |
dc.contributor.author | Gray, Nathanael S. | - |
dc.date.accessioned | 2021-09-05T02:27:42Z | - |
dc.date.available | 2021-09-05T02:27:42Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-12 | - |
dc.identifier.issn | 1552-4450 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/96612 | - |
dc.description.abstract | Her3 (also known as ErbB3) belongs to the epidermal growth factor receptor tyrosine kinases and is well credentialed as an anti-cancer target but is thought to be 'undruggable' using ATP-competitive small molecules because it lacks appreciable kinase activity. Here we report what is to our knowledge the first selective Her3 ligand, TX1-85-1, that forms a covalent bond with Cys721 located in the ATP-binding site of Her3. We demonstrate that covalent modification of Her3 inhibits Her3 signaling but not proliferation in some Her3-dependent cancer cell lines. Subsequent derivatization with a hydrophobic adamantane moiety demonstrates that the resultant bivalent ligand (TX2-121-1) enhances inhibition of Her3-dependent signaling. Treatment of cells with TX2-121-1 results in partial degradation of Her3 and serendipitously interferes with productive heterodimerization between Her3 with either Her2 or c-Met. These results suggest that small molecules will be capable of perturbing the biological function of Her3 and -60 other pseudokinases found in human cells. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | HER2-POSITIVE BREAST-CANCER | - |
dc.subject | TYROSINE KINASE | - |
dc.subject | LUNG-CANCER | - |
dc.subject | EXTENDED 5-SUBSTITUENT | - |
dc.subject | ADJUVANT CHEMOTHERAPY | - |
dc.subject | SELECTIVE INHIBITORS | - |
dc.subject | MET AMPLIFICATION | - |
dc.subject | OVARIAN-CANCER | - |
dc.subject | PROTEIN | - |
dc.subject | DOMAIN | - |
dc.title | Pharmacological targeting of the pseudokinase Her3 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Sim, Taebo | - |
dc.identifier.doi | 10.1038/nchembio.1658 | - |
dc.identifier.wosid | 000345122300007 | - |
dc.identifier.bibliographicCitation | NATURE CHEMICAL BIOLOGY, v.10, no.12, pp.1006 - + | - |
dc.relation.isPartOf | NATURE CHEMICAL BIOLOGY | - |
dc.citation.title | NATURE CHEMICAL BIOLOGY | - |
dc.citation.volume | 10 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1006 | - |
dc.citation.endPage | + | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | HER2-POSITIVE BREAST-CANCER | - |
dc.subject.keywordPlus | TYROSINE KINASE | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | EXTENDED 5-SUBSTITUENT | - |
dc.subject.keywordPlus | ADJUVANT CHEMOTHERAPY | - |
dc.subject.keywordPlus | SELECTIVE INHIBITORS | - |
dc.subject.keywordPlus | MET AMPLIFICATION | - |
dc.subject.keywordPlus | OVARIAN-CANCER | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | DOMAIN | - |
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