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

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. [Display omitted] •Novel small molecular CRM1 degrader.•Induce the apoptosis in gastric carcinoma.•Selective inhibition for the proliferation of gastric cancer.•Synergistic effects of compound 1l and MG132.