) The long term objective of this NCNPDDG is the identification of compounds suitable for development as antitumor agents. This is to be done by 1. utilizing existing, validated assay to guide the screening/isolation of novel DNA damaging agents, and inhibitors of DNA topoisomerase I, DNA topoisomerase II, DNA polymerase B and Myt1 kinase (Programs 1, 2 and 3) 2. developing new mechanism-based assays as high-throughput primary screens for natural products with potential activity in the treatment of cancer, including inhibitors of proliferation-linked signal transduction (Program 1) 3. fractionating lead extracts and characterizing isolated natural products derived from each of the assay systems as chemical entities and biological mediators (Programs 2 and 3) 4. developing and utilizing secondary discriminators to guide the focused identification of natural/products/structurally modified compounds predicted to have useful antitumor activity (Programs 1 and 3) 5. preparing in quantity and evaluating promising compounds in tumor cells (for mechanism, biochemical pharmacology, interaction with known antineoplastic agents) and in animal tumor models (Programs 1-3)

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (M2))
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
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University of Virginia
Schools of Arts and Sciences
United States
Zip Code
Cao, Shugeng; Murphy, Brian T; Foster, Caleb et al. (2009) Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases. Bioorg Med Chem 17:2276-81
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Prakash Chaturvedula, V S; Gao, Zhijie; Hecht, Sidney M et al. (2003) A new acylated oleanane triterpenoid from Couepia polyandra that inhibits the lyase activity of DNA polymerase beta. J Nat Prod 66:1463-5
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