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ID: ALA4619798
Journal: ACS Med Chem Lett
Title: Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase: Proof of Concept Study.
Authors: Yan VC, Yang KL, Ballato ES, Khadka S, Shrestha P, Arthur K, Georgiou DK, Washington M, Tran T, Poral AH, Pham CD, Yan MJ, Muller FL.
Abstract: Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of ENO1. 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 in vitro proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of enolase inhibition.
CiteXplore: 32676158