Document Detail


Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L).
MedLine Citation:
PMID:  19349174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-21
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  19     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-17     Completed Date:  2009-08-21     Revised Date:  2010-09-24    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  2429-34     Citation Subset:  IM    
Affiliation:
Laboratory of Cell Biology, NCI, NIH, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Amides / 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:
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:
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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