Many types of cancer become dependent on a constant supply of fatty acids supplied by fatty acid synthase (FAS), and therefore inhibitors of FAS are of interest to the scientific community. Even tool compounds are important for helping to study this altered metabolism in cancer. This project has its origins in a compound previously synthesized by others, with demonstrated potency against the thioesterase domain of FAS but with poor plasma stability in the mouse. We selected a change to the initial hit that would be expected to improve the plasma stability, yet also alters the overall size of the compound. A structure-activity relationship based on the new compound was undertaken in an attempt to optimize potency as measured by cell cytotoxicity on selected breast cancer cell lines. The results of this research will be presented along with the cell cytotoxicity and plasma stability of the new compounds.

Improving activity of a fatty acid synthase inhibitor by structural mimicry

251st National Meeting (2016)

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