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.

中文翻译：

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烯醇酶的可生物还原的氨基膦酸酯前药抑制剂：概念验证研究。

糖酵解抑制在癌症治疗中仍然令人向往。我们最近描述了一种有前途的膦酸酯烯醇酶抑制剂，用于掩盖ENO1纯合缺失的癌症。在这里，我们描述了硝基杂环磷酸氨基甲酸酯前药对的应用，以利用肿瘤缺氧。与低氧相比，该低氧条件下这种可生物还原的前药显示出大于2倍的效力，并且在生物流体中显示出强大的稳定性。我们的工作提供了强有力的体外概念验证，可以在烯醇酶抑制的背景下将生物还原用作药物的前送递策略。