2. Academic Validation
  3. Development of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent

Development of MBRI-001, a deuterium-substituted plinabulin derivative as a potent anti-cancer agent

  • Bioorg Med Chem Lett. 2017 Mar 15;27(6):1416-1419. doi: 10.1016/j.bmcl.2017.01.096.
Zhongpeng Ding 1,  Hejuan Cheng 1,  Shixiao Wang 2,  Yingwei Hou 3,  Jianchun Zhao 3,  Huashi Guan 3,  Wenbao Li 4
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs of Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.
  • 2 Marine Biomedical Research Institute of Qingdao, Qingdao 266071, People's Republic of China.
  • 3 Key Laboratory of Marine Drugs of Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, People's Republic of China.
  • 4 Key Laboratory of Marine Drugs of Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, People's Republic of China. Electronic address: wbli92128@ouc.edu.cn.
PMID: 28228362 DOI: 10.1016/j.bmcl.2017.01.096
Abstract

Plinabulin, a drug targeting microtubule of Cancer cells, has been currently tried in its phase III clinical study. However, low efficacy caused by poor pharmacokinetic (PK) properties has been considered to be the main obstacle to approved by the Food and Drug Administration. Herein, we introduced a deuterium atom as an isostere in its structure to become a new compound named (MBRI-001, No. 9 in a series of deuterium-substituted compounds). The structure of MBRI-001 was characterized by HRMS, NMR, IR and a single crystal analysis. MBRI-001 exhibited better pharmacokinetic characteristics than that of plinabulin. Additionally, its antitumor activity is in a low nanomolar level for a variety of Cancer cell lines and high activity against human NCI-H460 xenograted in mice intravenous administration. Importantly, continuous administration of MBRI-001 exhibited lower toxicity compared to docetaxel. We thus suggest that MBRI-001 could be developed as a promising anti-cancer agent in near future.

Keywords

Deuterium substituted; Docetaxel; Microtubule; Pharmacokinetic properties; Plinabulin.

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