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Shugeng Cao, Ph.D.
Associate Professor
Department of Pharmaceutical Sciences
The Daniel K. Inouye College of Pharmacy
University of Hawaii at Hilo

Hawaiian fungal metabolites as a source for the treatment of high-grade serous ovarian cancer

This study is to identify mtp53 R248 re-activators to restore its apoptotic function and thus, more specifically target HGSOC and other cancers carrying the same mtp53. Our published and unpublished data demonstrated that chetomin, an mtp53 R175H reactivator, was identified from an NCI natural product collection [Chem. Biol. 2015 Sep 17;22(9):1206-1216]. Importantly, chetomin was also isolated from a fungal sample in our lab’s natural product library, made of about 5,000 semi-pure fractions generated from strains that were selected from about 3,000 pure fungal strains. From our own natural product library, a few FT238-C15 (=FT238-28) analogs were recently identified as plausible mtp53R248 reactivators through a pilot screening [Org. Lett. 2016 May 20;18(10):2335-2338], and its novelty is tightly associated with our lab’s unique natural product library, since no other places are comparable to Hawaii in hosting a variety of fungi owing to the unique rainfall conditions here.
With the natural product library established, assays constructed, access to molecular biology, morphology core facilities accessible, and transgenic mice available, we are well equipped to carry out the studies. We will Identify natural products that can restore the functions of mtp53R248Q in HGSOC, and study the mechanism of the lead compound targeting mtp53R248 in HGSOC and other cancers.

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