Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists

被引：5

作者：

Zhou, Jia-Xu ^{[1
,2
]}

Li, Cui-Na ^{[2
]}

Liu, Ya-Meng ^{[2
]}

Lin, Su-Qin ^{[3
]}

Wang, Ying ^{[2
]}

Xie, Cen ^{[2
]}

Nan, Fa-Jun ^{[1
,2
,4
]}

机构：

[1] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[3] Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China

[4] Bohai Rim Adv Res Inst Drug Discovery, Drug Discovery Shandong Lab, Yantai 264117, Shandong, Peoples R China

来源：

ACS OMEGA | 2022年 / 7卷 / 20期

基金：

中国国家自然科学基金;

关键词：

FARNESOID-X-RECEPTOR; NUCLEAR RECEPTOR; BILE-ACIDS; POTENT;

D O I：

10.1021/acsomega.2c01567

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The farnesoid X receptor (FXR) plays an important role in the regulation of bile acid, lipid, and glucose homeostasis. Recent findings have shown that the inhibition of FXR is beneficial to improvement of related metabolic diseases and cholestasis. In the present work, 9,11-seco-cholesterol derivatives were designed and synthesized by cleaving the C ring of cholesterol and were identified as novel structures of FXR antagonists. Compound 9a displayed the best FXR antagonistic activity at the cellular level (IC50 = 4.6 mu M) and decreased the expression of the target genes of FXR in vivo.

引用

页码：17401 / 17405

页数：5

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