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Bioreducible Pro-drug Inhibitors of Enolase

preprint
submitted on 26.03.2020 and posted on 26.03.2020 by Victoria Yan, Kristine Yang, Elliot Ballato, Kenisha Arthur, Dimitra Georgiou, Florian Muller
Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of Enolase for cancers harboring deletions in ENO1. Here, we describe the application of nitroheterocycle pro-drugs capitalizing on tumor hypoxia. These bioreducible pro-drugs exhibit up to 14-fold greater potency under hypoxic conditions compared to normoxia and exhibit robust stability in biological fluids. Our work provides strong proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of Enolase inhibition.

Funding

American Cancer Society

National Comprehensive Cancer Network

History

Email Address of Submitting Author

victoriacyanide@gmail.com

Institution

University of Texas MD Anderson Cancer Center

Country

USA

ORCID For Submitting Author

0000-0003-0837-5184

Declaration of Conflict of Interest

F.L.M., V.C.Y., K.L.Y., and E.S.B. are on a patent application describing second-generation pro-drug inhibitors of Enolase.

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