Discovery of BC-01, a novel mutual prodrug (hybrid drug) of ubenimex and fluorouracil as anticancer agent
Discovery of BC-01, a novel mutual prodrug (hybrid drug) of ubenimex and fluorouracil as anticancer agent
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发现 BC-01，一种新型抗癌药物乌苯美司和氟尿嘧啶的相互前药（混合药物）
DOI：
10.1016/j.ejmech.2016.05.068
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发表时间：
2016-10-04
影响因子：
6.7
通讯作者：
Zhang, Yingjie
中科院分区：
文献类型：
--
作者：
Jiang, Yuqi;Li, Xiaoyang;Zhang, Yingjie
我们设计并合成了一种新型的相互前药，命名为BC-01（3），将乌苯美司和氟尿嘧啶（5-FU）整合到一个分子中，基于先前的研究结果，表明氨肽酶N（CD 13）抑制剂乌苯美司和细胞毒性抗肿瘤剂5-FU的组合在体外和体内显示出提高的抗肿瘤效率。3对CD 13酶活性具有较强的抑制活性。与乌苯美司相比，3具有更强的抗血管生成作用，与已批准的5-FU前药卡培他滨相比，3具有更强的肿瘤生长抑制和抗转移作用。此外，与5-FU或5-FU加乌苯美司相比，3甚至在我们的5-FU耐药小鼠模型中也表现出上级抗肿瘤效率。其他抗肿瘤药物可以使用这种策略与乌苯美司偶联，以获得具有良好抗肿瘤效力的新型相互前药。(C)2016 Elsevier Masson SAS。All rights reserved.
We designed and synthesized a novel mutual prodrug, named BC-01 (3), by integrating ubenimex and Fluorouracil (5-FU) into one molecule based on prior research results that showed that a combination of the aminopeptidase N (CD13) inhibitor, ubenimex, and the cytotoxic antitumor agent, 5-FU, exhibited improved in vitro and in vivo antitumor efficiency. 3 showed potent inhibitory activity against CD13 enzymatic activity. Compared with ubenimex, 3 exhibited more potent anti-angiogenesis effects, and compared with the approved 5-FU prodrug, capecitabine, 3 exhibited more potent tumor growth inhibitory and anti-metastasis effects. Additionally, compared with 5-FU or 5-FU plus ubenimex, 3 also exhibited a superior antitumor efficiency even in our 5-FU-resistant mice model. Other antitumor agents could be conjugated with ubenimex using this strategy to obtain novel mutual prodrugs with promising antitumor potency. (C) 2016 Elsevier Masson SAS. All rights reserved.