2. Academic Validation
  3. 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

  • Eur J Med Chem. 2016 Oct 4:121:649-657. doi: 10.1016/j.ejmech.2016.05.068.
Yuqi Jiang 1,  Xiaoyang Li 1,  Jinning Hou 1,  Yongxue Huang 2,  Yuping Jia 3,  Mingming Zou 1,  Jian Zhang 4,  Xuejian Wang 5,  Wenfang Xu 6,  Yingjie Zhang 7
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, PR China.
  • 2 Weifang Bochuang International Biological Medicinal Institute, Weifang, Shandong, 261061, PR China.
  • 3 Shandong Academy of Pharmaceutical Sciences, Ji'nan, Shandong, 250101, PR China.
  • 4 College of Pharmacy, Weifang Medical University, 261053, Wei'fang, Shandong, PR China.
  • 5 College of Pharmacy, Weifang Medical University, 261053, Wei'fang, Shandong, PR China. Electronic address: wangxuejian@wfmc.edu.cn.
  • 6 Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, PR China. Electronic address: wenfxu@163.com.
  • 7 Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, PR China. Electronic address: zhangyingjie@sdu.edu.cn.
PMID: 27322756 DOI: 10.1016/j.ejmech.2016.05.068
Abstract

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.

Keywords

Anti-metastasis; Antitumor; CD13; Liver cancer; Mutual prodrug; Ubenimex.

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