Bioreducible Pro-drug Inhibitors of Enolase

26 March 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

pro-drug
hypoxia
glycolysis inhibitor
Targeted Therapy

Supplementary materials

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