Discovery of structurally novel and potentially very important cancer drugs from animal, plant and microorganism sources will continue to form the sharply focused objective of the renewal Outstanding Investigator Grant (OIG) research for the National Cancer Institute (NCI). To provide the best candidates for eventual clinical trial among the current outstanding marine animal and plant anticancer substances we have discovered in collaboration with the spongistatins, dolastatins, halistatins and cephalostatins, additional emphasis will be placed on obtaining new members of these series and elucidating their structures while further advancing research knowledge necessary to the expanding clinical trials of bryostatin 1. Vigorous parallel research will continue to be strongly focused on the isolation, characterization and structural determination of new and potentially useful anticancer drugs from marine animals, plants and microorganisms. The OIG program would be used to isolate and characterize such new anticancer drugs from confirmed active extracts of marine invertebrates and vertebrates, marine and terrestrial plants, and marine microorganisms. The principal focus would be upon marine animal and plant species yielding extracts with an outstanding level of confirmed activity in the NCI's human cancer cell systems, murine xenografts and where appropriate, new microorganism and biochemical type preselection methods. Only those species that give maximum promise of yielding new drugs with potential clinical activity will be pursued with OIG funds. Other such leads of a lesser priority will be pursued with any other financial support that might be available. Because of 36 years devoted exclusively to constructing the foundation for this anticancer drug discovery research, a good number of exceedingly promising animal, microorganism and plant species have already been uncovered and will be used along with newly developed leads to maintain a very productive output of potentially useful antineoplastic substances of unique structure. As in the past the renewal OIG program will greatly assist the DCT-NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the overall renewal OIG program will be sharply focused on the discovery and very rapid development of new anticancer drugs for the National Cancer Institute's programs directed at improving human cancer treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA044344-07
Application #
2091430
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1989-06-01
Project End
2001-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
188435911
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Kedei, Noemi; Kraft, Matthew B; Keck, Gary E et al. (2015) Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships. J Nat Prod 78:896-900
Lubahn, Cheri; Schaller, Jill A; Shewmacker, Eric et al. (2012) Preclinical efficacy of sodium narcistatin to reduce inflammation and joint destruction in rats with adjuvant-induced arthritis. Rheumatol Int 32:3751-60
Pettit, George R; Minardi, Mathew D; Hogan, Fiona et al. (2010) An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins. J Nat Prod 73:399-403
Pettit, George R; Knight, John C; Herald, Delbert L et al. (2009) Antineoplastic agents. 570. Isolation and structure elucidation of bacillistatins 1 and 2 from a marine Bacillus silvestris. J Nat Prod 72:366-71
Pettit, Robin K; Pettit, George R; Hamel, Ernest et al. (2009) E-Combretastatin and E-resveratrol structural modifications: antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes. Bioorg Med Chem 17:6606-12
Pettit, George R; Ducki, Sylvie; Eastham, Stephen A et al. (2009) Antineoplastic agents. 454. Synthesis of the strong cancer cell growth inhibitors trans-dihydronarciclasine and 7-deoxy-trans-dihydronarciclasine (1a). J Nat Prod 72:1279-82
Pettit, George R; Hu, Shougang; Knight, John C et al. (2009) Antineoplastic agents. 571. Total synthesis of bacillistatin 2. J Nat Prod 72:372-9
Brennan, Mary R; Costello, Catherine E; Maleknia, Simin D et al. (2008) Stylopeptide 2, a proline-rich cyclodecapeptide from the sponge Stylotella sp. J Nat Prod 71:453-6
Pettit, George R; Hogan, Fiona; Xu, Jun-Ping et al. (2008) Antineoplastic agents. 536. New sources of naturally occurring cancer cell growth inhibitors from marine organisms, terrestrial plants, and microorganisms(1a,). J Nat Prod 71:438-44
Pettit, George R; Smith, Thomas H; Feng, Song et al. (2007) Antineoplastic agents. 561. Total synthesis of respirantin. J Nat Prod 70:1073-83

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