Zhou Jia-Xu, Li Cui-Na, Liu Ya-Meng, Lin Su-Qin, Wang Ying, Xie Cen, Nan Fa-Jun
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, People's Republic of China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
ACS Omega. 2022 May 12;7(20):17401-17405. doi: 10.1021/acsomega.2c01567. eCollection 2022 May 24.
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 displayed the best FXR antagonistic activity at the cellular level (IC = 4.6 μM) and decreased the expression of the target genes of FXR .
法尼醇X受体（FXR）在胆汁酸、脂质和葡萄糖稳态的调节中发挥着重要作用。最近的研究结果表明，抑制FXR有助于改善相关代谢疾病和胆汁淤积。在本研究中，通过切割胆固醇的C环设计并合成了9,11-开环胆固醇衍生物，并将其鉴定为FXR拮抗剂的新结构。化合物在细胞水平上表现出最佳的FXR拮抗活性（IC = 4.6 μM），并降低了FXR靶基因的表达。
