) The long term objective of this Laboratory Program is the identification of compounds suitable for development as antitumor agents. During the project period, objectives include: (1) identifying mechanistically unique DNA damaging agents (2) obtaining more potent inhibitors of DNA polymerase beta so that it is possible to complete the testing of the hypothesis that these agents can potentiate the cytotoxic activity of antitumor agents that act by creating DNA lesions, and demonstrating the ability of such inhibitors to potentiate the antitumor activity of agents such as bleomycin, esperamicin and califcheamicin (3) fractionating prioritized extracts identified by Program 1 to isolate and structurally characterize the natural principle(s) (4) prioritizing the lead compounds identified by the studies outlined above and obtaining the most promising compounds in quantities sufficient for antitumor evaluation in experimental animal models/initial preclinical development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA050771-13
Application #
6662766
Study Section
Project Start
2002-09-18
Project End
2003-05-31
Budget Start
Budget End
Support Year
13
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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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
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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