) 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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19CA050771-11
Application #
6166332
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (M2))
Program Officer
Lees, Robert G
Project Start
2000-09-30
Project End
2005-05-31
Budget Start
2000-09-30
Budget End
2001-05-31
Support Year
11
Fiscal Year
2000
Total Cost
$533,165
Indirect Cost
Name
University of Virginia
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Prakash Chaturvedula, V S; Schilling, Jennifer K; Johnson, Randall K et al. (2003) New cytotoxic lupane triterpenoids from the twigs of Coussarea paniculata. J Nat Prod 66:419-22
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
Zhou, B N; Johnson, R K; Mattern, M R et al. (2001) The first naturally occurring Tie2 kinase inhibitor. Org Lett 3:4047-9

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