This is a component of a NCNPDDG proposal that is submitted in response to RFA 94-CA-07. The overall objective of this research proposal is to discover and develop new drugs for the treatment of cancer. The role of Dr. Faulkner's research group in the collaborative research program is to isolate and identify novel antitumor agents from marine organisms, primarily sponges and marine molluscs. An important difference between this proposal and other research projects is that the specimens to be studied will be selected on the basis of the activity of their crude extracts in bioassays performed by Bristol-Myers Squibb (BMS) and that the isolation will be guided, wherever possible, by bioassays performed at Scripps Institution of Oceanography (SIO) or BMS. Once a compound is recognized as potentially suitable for clinical development, it will be identified using non-destructive methods. If required, we will recollect large quantities of the source organisms, verify the authenticity of the samples and develop methods for large scale extraction and purification of sufficient material to allow BMS to fully evaluate the compound. In a limited number of cases, we expect to provide derivatives of a lead compound for evaluation but we expect that any total syntheses will be performed by BMS chemists. Within the collaborative project, Dr. Faulkner's group will have primary responsibility for studies on sponges and marine molluscs with secondary responsibilities in the general area of other marine invertebrates and macroscopic algae. We will establish collection protocols for sponges and molluscs and we will be responsible for their identification and recollection. We propose to introduce a more chemotaxonomically-driven collection strategy to take advantage of Mary Kay Harper's expertise in sponge taxonomy. We anticipate that this project will quickly generate an appreciable number of active extraCts for isolation studies. During the start-up period we will work on completion of four projects started during the current NCNPDDG program and we expect to work on new leads generated as the current set of extracts are screened in a wider range of mechanism-based assays.
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