This is a competitive renewal application to continue to explore marine microorganisms as a new source for antitumor-antibiotics. The proposed project would continue as a collaboration between chemists and microbiologists at the Scripps Institution of Oceanography in La Jolla, CA. and cancer biologists at the Bristol-Myers Squibb Pharmaceutical Research Institute in Princeton, NJ. Studies proposed for the renewal period include the following: - The isolation, cultivation and biological evaluation of marine microorganisms from diverse habitats. The focus of the renewal application will be on 7 new groups of obligate marine actinomycetes (Salinospora, Marinomyces, and the MAR 3-7 groups) discovered during the past 24 months. - Overall, to continue to isolate and describe new molecules which show novel mechanisms of action in cancer-relevant, mechanism-based screens, show in vitro tissue type selectivity in the NCI 60 cell line and BMS ODCA panels, and to subsequently investigate their in vivo efficacies. - To focus a screening effort on the new cancer relevant targets IGF-1 Growth Factor, DMA Methyl Transferase-1 (DNMT-1), CoactivatorAssociated Arginine Methyltransferase (CARM-1) and Ceramidase, and on yeast selective DMA repair and cell checkpoint targets. These goals will also be supplemented at SIO with several assays which focus on infectious diseases (screening against drug resistant pathogens and for inhibitors of two selected bacterial efflux pumps). - To continue to advance previous discoveries (Salinosporamide A, Halimide, Sargassamide A and several other molecules) for in vivo evaluation in the BMS P388 and L1210 leukemias and the murine solid tumor models M109, Mam16/C and M50766.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA044848-26
Application #
8230782
Study Section
Special Emphasis Panel (NSS)
Program Officer
Fu, Yali
Project Start
1987-04-15
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
26
Fiscal Year
2012
Total Cost
$373,010
Indirect Cost
$131,580
Name
University of California San Diego
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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