烯醇化酶的可生物还原磷酰胺前药抑制剂：概念验证研究
Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase: Proof of Concept Study.
作者信息
Yan Victoria C, Yang Kristine L, Ballato Elliot S, Khadka Sunada, Shrestha Prakriti, Arthur Kenisha, Georgiou Dimitra K, Washington Mykia, Tran Theresa, Poral Anton H, Pham Cong-Dat, Yan Matthew J, Muller Florian L
机构信息
Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States.
Department of Biology, Mount Holyoke College, South Hadley, Massachusetts 01075, United States.
出版信息
ACS Med Chem Lett. 2020 Jun 22;11(7):1484-1489. doi: 10.1021/acsmedchemlett.0c00203. eCollection 2020 Jul 9.
Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of . 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 proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of enolase inhibition.
糖酵解抑制在癌症治疗中仍是一个理想目标。我们最近描述了一种有前景的烯醇酶膦酸酯抑制剂，用于存在某基因纯合缺失的癌症。在此，我们描述了一种硝基杂环膦酰胺前药对的应用，以利用肿瘤缺氧环境。这种可生物还原的前药在缺氧条件下比常氧条件下表现出超过2倍的效力，并且在生物流体中具有强大的稳定性。我们的工作为在烯醇酶抑制背景下将生物还原作为一种前药递送策略提供了有力的概念验证。
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