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.
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DOI：
10.1016/j.ejmech.2020.112708
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发表时间：
2020-08
影响因子：
6.7
通讯作者：
Hai-wei Xu;Shilong Jia;Mengbo Liu;Xiaobo Li;Xia Meng;Xinxin Wu;Lu Yu;Menglin Wang;Cheng-yun Jin
中科院分区：
文献类型：
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作者：
Hai-wei Xu;Shilong Jia;Mengbo Liu;Xiaobo Li;Xia Meng;Xinxin Wu;Lu Yu;Menglin Wang;Cheng-yun Jin
染色体区域维持蛋白1（CRM 1）是几种肿瘤抑制因子的唯一核输出蛋白，是一种生长调节蛋白，是一个很有吸引力的抗癌药物靶点。本工作以天然产物哥尼撒明为基础，从新合成的α，β-不饱和-δ-内酯中发现了一种新型的CRM 1降解剂。它通过分级CRM 1诱导MGC 803和HGC 27细胞系凋亡。与人胃粘膜上皮细胞株（GES 1）相比，对胃癌细胞株MGC 803、HGC 27的增殖具有选择性抑制作用。首次研究了CRM 1抑制剂或降解剂诱导胃癌细胞凋亡的作用。
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 linesviadegrading 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.