Continued discovery of novel and potentially important cancer chemotherapeutic drugs from animal and plant sources will form the sharply focused objective of the overall Outstanding Investigator Grant (OIG) program with the National Cancer Institute (NCI). In order to provide the best choices for eventual clinical trial among the very important bryostatins, dolastatins, pancratistatin and the phyllanthostatins (phyllanthoside) recently discovered in our institute's collaborative research programs with the NCI, increased efforts will be devoted to uncovering additional members of each series and subjecting them to structural elucidation. While this important research is in progress a long-term study directed at the isolation, characterization and structural elucidation of new and potentially useful anticancer drugs from marine animals and plants will be continued. Financial support provided by the OIG program would be used to isolate and characterize such new cancer chemotherapeutic drugs from confirmed active extracts of marine invertebrates and vertebrates as well as marine terrestrial plants. The principal focus would be upon marine animal and plant species yielding extracts with an outstanding level of confirmed activity (T/C >150) in the NCI's murine P-388 lymphocytic leukemia, the NCI human caner cell systems, and later using, in part, new micro-organism and biochemical type preselection methods now under evaluation. Only those species that give maximum promise of yielding new drugs at a potential clinical level of interest will be pursued as part of the OIG research. Other such leads of a lesser priority will be pursued with any other financial support that might be available at that time. Because of 30 years spent building the foundation for this anticancer drug discovery research, a good number of exceedingly promising animal 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. The OIOG program proposed will be of great assistance to the NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the overall OIG program will be sharply focused on the discovery and very rapid development of new anticancer and HIV drugs for the national Cancer Institute's programs directed at improving human cancer and AIDS treatment.
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