Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase: Proof of Concept Study.
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ABSTRACT:
SUBMITTER: Yan VC
PROVIDER: S-EPMC7357215 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase: Proof of Concept Study.
Yan Victoria C VC Yang Kristine L KL Ballato Elliot S ES Khadka Sunada S Shrestha Prakriti P Arthur Kenisha K Georgiou Dimitra K DK Washington Mykia M Tran Theresa T Poral Anton H AH Pham Cong-Dat CD Yan Matthew J MJ Muller Florian L FL
ACS medicinal chemistry letters 20200622 7
Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of <i>ENO1</i>. Here, we describe the application of a nitroheterocycle phosphonoamidate pro-drug pair to capitalize on tumor hypoxia. This bioreducible prodrug exhibits greater-than 2-fold potency under hypoxic conditions compared to normoxia and exhibits robust stability in biological fluids. Our work provides strong <i>in v ...[more]
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