| Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L). | |
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MedLine Citation:
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PMID: 19349174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cancer cells evade death by over-producing specific proteins that inhibit apoptosis. One such group of proteins is the Bcl-2 family, of which Bcl-x(L) is an important member. This protein binds and inhibits BAK, another protein that promotes apoptosis. While the development of chemical inhibitors that block Bcl-x(L)-BAK association have been the focus of intense research efforts, we demonstrate in this manuscript an alternative strategy to downregulate Bcl-x(L). We have identified a small molecule (Bang52) that induces apoptosis in a lymphoblast-derived cell line by lowering levels of Bcl-x(L). Since Bang52 bears no resemblance to any chemical binder of Bcl-x(L) we believe that degradation of the protein is stimulated by a new type of pathway. These findings highlight a novel approach to the development of small molecules that promote apoptosis. |
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Authors:
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Matteo Rossi; Jeong-Kyu Bang; Sharlyn Mazur; Jaclyn A Iera; Darren C Phillips; Gerard P Zambetti; Daniel H Appella |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-03-21 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 19 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-17 Completed Date: 2009-08-21 Revised Date: 2010-09-24 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 2429-34 Citation Subset: IM |
Affiliation:
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Laboratory of Cell Biology, NCI, NIH, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amides
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chemical synthesis*,
pharmacology Antineoplastic Agents / chemical synthesis*, pharmacology Apoptosis* Cell Line, Tumor Cell Separation Chemistry, Pharmaceutical / methods Down-Regulation Drug Design Drug Resistance, Neoplasm Flow Cytometry Gene Expression Regulation, Neoplastic* Humans Hydrocarbons, Fluorinated / chemical synthesis*, pharmacology Models, Chemical Tumor Suppressor Protein p53 / metabolism bcl-X Protein / biosynthesis* |
| Grant Support | |
ID/Acronym/Agency:
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CA21765/CA/NCI NIH HHS; CA6320/CA/NCI NIH HHS; Z01 DK031123-03/DK/NIDDK NIH HHS; Z01 DK031123-04/DK/NIDDK NIH HHS; ZIA DK031123-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Antineoplastic Agents; 0/Bang52; 0/Hydrocarbons, Fluorinated; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-X Protein |
| Comments/Corrections | |
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