2. Academic Validation
  3. Discovery of a cinnamyl piperidine derivative as new neddylation inhibitor for gastric cancer treatment

Discovery of a cinnamyl piperidine derivative as new neddylation inhibitor for gastric cancer treatment

  • Eur J Med Chem. 2021 Dec 15;226:113896. doi: 10.1016/j.ejmech.2021.113896.
Bo Wang 1,  Qiu-Hua Zhang 2,  Xiao-Jing Li 2,  Sai-Qi Wang 3,  Xiao-Bing Chen 4,  Bin Yu 5,  Hong-Min Liu 6
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China; Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
  • 2 School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China.
  • 3 Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Cancer Institute, Zhengzhou 450008, China.
  • 4 Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Cancer Institute, Zhengzhou 450008, China. Electronic address: [email protected].
  • 5 School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100000, China. Electronic address: [email protected].
  • 6 School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou 450001, China. Electronic address: [email protected].
PMID: 34624825 DOI: 10.1016/j.ejmech.2021.113896
Abstract

Targeting neddylation pathway has been recognized as an attractive Anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is highly desirable. Our work reported the discovery of novel cinnamyl piperidine compounds and their antitumor activity in vitro and in vivo. Among these compounds, compound 4g was identified as a novel neddylation inhibitor and decreased the neddylation levels of cullin 1, cullin 3 and cullin 5. Mechanistic studies demonstrated that compound 4g could inhibit the migration ability of gastric Cancer cells and induce Apoptosis partly mediated by the Nrf2-Keap1 pathway. Furthermore, in vivo anti-tumor studies showed that 4g effectively inhibited tumor growth without obvious toxicity. Collectively, the cinnamyl piperidine derivatives could serve as new lead compounds for developing highly effective neddylation inhibitors for gastric Cancer therapy.

Keywords

Cinnamyl piperidine; Gastric cancer; Neddylation inhibition.

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