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DC Field | Value | Language |
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dc.citation.endPage | 662 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 641 | - |
dc.citation.title | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 50 | - |
dc.contributor.author | Bruncko, Milan | - |
dc.contributor.author | Oost, Thorsten K. | - |
dc.contributor.author | Belli, Barbara A. | - |
dc.contributor.author | Ding, Hong | - |
dc.contributor.author | Joseph, Mary K. | - |
dc.contributor.author | Kunzer, Aaron | - |
dc.contributor.author | Martineau, Darlene | - |
dc.contributor.author | McClellan, William J. | - |
dc.contributor.author | Mitten, Michael | - |
dc.contributor.author | ng, Shi-Chu Ng | - |
dc.contributor.author | Nimmer, Paul M. | - |
dc.contributor.author | Oltersdorf, Tilman | - |
dc.contributor.author | Park, Cheol-Min | - |
dc.contributor.author | Petros, Andrew M. | - |
dc.contributor.author | Shoemaker, Alexander R. | - |
dc.contributor.author | Song, Xiaohong | - |
dc.contributor.author | Wang, Xilu | - |
dc.contributor.author | Wendt, Michael D. | - |
dc.contributor.author | Zhang, Haichao | - |
dc.contributor.author | Fesik, Stephen W. | - |
dc.contributor.author | Rosenberg, Saul H. | - |
dc.contributor.author | Elmore, Steven W. | - |
dc.date.accessioned | 2023-12-22T09:36:58Z | - |
dc.date.available | 2023-12-22T09:36:58Z | - |
dc.date.created | 2014-11-10 | - |
dc.date.issued | 2007-02 | - |
dc.description.abstract | verexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide. | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, v.50, no.4, pp.641 - 662 | - |
dc.identifier.doi | 10.1021/jm061152t | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.scopusid | 2-s2.0-33847404358 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/8553 | - |
dc.identifier.url | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33847404358 | - |
dc.identifier.wosid | 000244224900008 | - |
dc.language | 영어 | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Studies leading to potent, dual inhibitors of bcl-2 and Bcl-xL | - |
dc.type | Article | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | CASPASE ACTIVATION | - |
dc.subject.keywordPlus | FAMILY PROTEINS | - |
dc.subject.keywordPlus | CELL-LINES | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | LIFE | - |
dc.subject.keywordPlus | ANTAGONISTS | - |
dc.subject.keywordPlus | MECHANISMS | - |
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