U19 CA 50771
Natural Products Discovery - Nuclear & Signaling Targets
Natural Products Discovery - Nuclear & Signaling Targets
SEPTEMBER 29, 1989 - MAY 31, 2005 | |
PRINCIPAL INVESTIGATOR |
Sidney M. Hecht, Ph.D.
Department of Chemistry University of Virginia Charlottesville, VA 22904-4319 (804) 924-3906 |
ABSTRACT | |
(Description provided by applicant) | |
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)
PROGRAMS:
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