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Dounay Research: New Approaches to Treating Cancer, Neurodegeneration

Assistant Professor of Chemistry and Biochemistry Amy Dounay '96 has a new paper published in the Journal of Medicinal Chemistry. Her article, "Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway," looks at the emerging opportunities and significant challenges associated with pharmacological modulation of three enzymes in kynurenine pathway.

Dounay notes that the kynurenine pathway is responsible for the metabolism of more than 95 percent of dietary tryptophan and produces numerous bioactive metabolites. Recent studies have focused on three enzymes in this pathway: indoleamine dioxygenase (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT II). Dounay co-authored this article with former Pfizer colleagues Jamison Tuttle and Patrick Verhoest. "Our research team at Pfizer had reported some breakthrough discoveries in our medicinal chemistry studies toward KAT II inhibitors, designed to treat cognitive impairment associated with schizophrenia. Based on our work in this area, the editor of the Journal of Medicinal Chemistry invited us to write this article on the current state of research on the kynurenine pathway, which presents exciting opportunities for new drug discovery," Dounay said.

IDO1 inhibitors represent a "hot new area of research for cancer therapy," notes Dounay. Several clinical trials currently are underway to investigate IDO1 inhibitors as new "immunotherapy" approaches for the treatment of cancer. These agents also may have therapeutic uses in neurological disorders, including multiple sclerosis. "KMO inhibitors also are being investigated as potential treatments for neurodegenerative diseases, such as Huntington's and Alzheimer's," she said. The design of novel, potent, and selective inhibitors for each of these enzymes "could provide breakthrough treatments for numerous diseases, but significant research must still be completed in order to bring new medicines to patients," she said.

Dounay completed her Ph.D. in organic chemistry in 2001 at the University of Minnesota, where she focused on the synthesis of complex marine natural products. She completed NIH-funded postdoctoral training in organic synthesis at the University of California, Irvine. Dounay worked in the Neuroscience Medicinal Chemistry group at Pfizer from 2004-12, returning to CC as an assistant professor in the Department of Chemistry and Biochemistry in 2012. Her current research interests include the design and synthesis of new medicines for human African trypanosomiasis (sleeping disease) and other tropical diseases.

Report an issue - Last updated: 12/16/2020