These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 26.03.2020 and posted on 26.03.2020by 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.