Journal of Biomolecular Screening

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
1087057108315038v1
13/3/229    most recent
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sasiela, C. A.
Right arrow Articles by O'Keefe, B. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sasiela, C. A.
Right arrow Articles by O'Keefe, B. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
This version was published on March 1, 2008
Journal of Biomolecular Screening, Vol. 13, No. 3, 229-237 (2008)
DOI: 10.1177/1087057108315038

Identification of Inhibitors for MDM2 Ubiquitin Ligase Activity from Natural Product Extracts by a Novel High-Throughput Electrochemiluminescent Screen

Christy A. Sasiela

Molecular Targets Development Program, National Cancer Institute, Frederick, Maryland

David H. Stewart

Meso Scale Discovery, Gaithersburg, Maryland

Jirouta Kitagaki

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland

Yassamin J. Safiran

Meso Scale Discovery, Gaithersburg, Maryland

Yili Yang

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland

Allan M. Weissman

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland

Pankaj Oberoi

Meso Scale Discovery, Gaithersburg, Maryland

Ilia V. Davydov

Meso Scale Discovery, Gaithersburg, Maryland

Ekaterina Goncharova

Molecular Targets Development Program, National Cancer Institute, Frederick, Maryland

John A. Beutler

Molecular Targets Development Program, National Cancer Institute, Frederick, Maryland

James B. Mcmahon

Molecular Targets Development Program, National Cancer Institute, Frederick, Maryland

Barry R. O'Keefe

Molecular Targets Development Program, National Cancer Institute, Frederick, Maryland, okeefe{at}ncifcrf.gov

High-throughput screening technologies have revolutionized the manner in which potential therapeutics are identified. Although they are the source of lead compounds for ~65% of anticancer and antimicrobial drugs approved by the Food and Drug Administration between 1981 and 2002, natural products have largely been excluded from modern screening programs. This is due, at least in part, to the inherent difficulties in testing complex extract mixtures, which often contain nuisance compounds, in modern bioassay systems. In this article, the authors present a novel electrochemiluminescent assay system for inhibition of MDM2 activity that is suitable for testing natural product extracts in high-throughput screening systems. The assay was used to screen more than 144,000 natural product extracts. The authors identified 1 natural product, sempervirine, that inhibited MDM2 auto-ubiquitination, MDM2-mediated p53 degradation, and led to accumulation of p53 in cells. Sempervirine preferentially induced apoptosis in transformed cells expressing wild-type p53, suggesting that it could be a potential lead for anticancer therapeutics. (Journal of Biomolecular Screening 2008:229-237)

Key Words: high-throughput screening • MDM2 • ubiquitin • electrochemiluminescent screen • natural product extracts


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?