2. Academic Validation
  3. A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27

A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27

  • Eur J Med Chem. 2020 Nov 15;206:112708. doi: 10.1016/j.ejmech.2020.112708.
Hai-Wei Xu 1,  Shilong Jia 2,  Mengbo Liu 2,  Xiaobo Li 2,  Xia Meng 2,  Xinxin Wu 2,  Lu Yu 2,  Menglin Wang 2,  Cheng-Yun Jin 3
Affiliations

Affiliations

  • 1 Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou University, No. 100, KeXueDaDao, Zhengzhou, 450001, China. Electronic address: [email protected].
  • 2 Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China.
  • 3 Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou University, No. 100, KeXueDaDao, Zhengzhou, 450001, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, PR China. Electronic address: [email protected].
PMID: 32810752 DOI: 10.1016/j.ejmech.2020.112708
Abstract

Chromosome region maintenance 1 (CRM1) is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive Cancer drug target. In the present work, a novel CRM1 degrader was discovered from newly synthesized α, β-unsaturated-δ-lactone based on a natural product Goniothalamin. It induces Apoptosis of both MGC803 and HGC27 cell lines via degrading CRM1. Selective inhibition was observed for the proliferation of gastric Cancer cell lines MGC803, HGC27 comparing to Human Gastric Mucosal Epithelial Cell Line (GES1). For the first time, CRM1 Inhibitor or degrader inducing Apoptosis in gastric carcinoma was investigated.

Keywords

CRM1/XPO1; Degrader; Gastric cancer; Structure-activity relationship; Synthesis.

Figures
Products