2. Academic Validation
  3. Discovery of a novel chimeric ubenimex-gemcitabine with potent oral antitumor activity

Discovery of a novel chimeric ubenimex-gemcitabine with potent oral antitumor activity

  • Bioorg Med Chem. 2016 Nov 15;24(22):5787-5795. doi: 10.1016/j.bmc.2016.09.033.
Yuqi Jiang 1,  Jinning Hou 1,  Xiaoyang Li 1,  Yongxue Huang 2,  Xuejian Wang 3,  Jingde Wu 1,  Jian Zhang 3,  Wenfang Xu 1,  Yingjie Zhang 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China.
  • 2 Weifang Bochuang International Biological Medicinal Institute, Weifang, Shandong 261061, PR China.
  • 3 College of Pharmacy, Weifang Medical University, 261053 Weifang, Shandong, PR China.
  • 4 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China. Electronic address: zhangyingjie@sdu.edu.cn.
PMID: 27670098 DOI: 10.1016/j.bmc.2016.09.033
Abstract

Herein, a novel mutual prodrug BC-A1 was discovered by integrating ubenimex and gemcitabine into one molecule. Biological characterization revealed that compound BC-A1 could maintain both the anti-CD13 activity of ubenimex and the cytotoxic activity of gemcitabine in vitro. Further characterization also demonstrated that compound BC-A1 exhibited significant anti-invasion and anti-angiogenesis effects in vitro. The preliminary stability test of BC-A1 revealed that it could release gemcitabine in vitro. The in vivo anti-tumor results in liver Cancer showed that at the same dosage, oral administration of BC-A1 was as potent as intraperitoneal administration of gemcitabine. This warranted the further research and development of the orally active prodrug BC-A1 because gemcitabine can not be orally administrated in clinic.

Keywords

Anti-angiogenesis; Anticancer; CD13 inhibitor; Gemcitabine (GEM); Ubenimex.

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