U19 CA 50771
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:

  1. Signaling/Nuclear Targets for Natural Products Drug Discovery; John S. Lazo, Ph.D., University of Pittsburgh School of Medicine
  2. Isolation of Novel Mechanism-Based Antitumor Agents; David G. I. Kingston, Ph.D., Virginia Polytechnic Institute and State University
  3. Nuclear Targets for Natural Products Drug Discovery; Sidney M. Hecht, Ph.D., University of Virginia
  4. Natural Products Extracts for Drug Discovery, Steven C. Bobzin, Ph.D., Galileo Laboratories