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

Content Provider	Europe PMC
Author	Zhou, Jia-Xu Li, Cui-Na Liu, Ya-Meng Lin, Su-Qin Wang, Ying Xie, Cen Nan, Fa-Jun
Copyright Year	2022
Abstract	The farnesoid X receptor(FXR) plays an important role in the regulationof bile acid, lipid, and glucose homeostasis. Recent findings haveshown that the inhibition of FXR is beneficial to improvement of relatedmetabolic diseases and cholestasis. In the present work, 9,11-seco-cholesterolderivatives were designed and synthesized by cleaving the C ring ofcholesterol and were identified as novel structures of FXR antagonists.Compound 9a displayed the best FXR antagonistic activityat the cellular level (IC50 = 4.6 μM) and decreasedthe expression of the target genes of FXR in vivo.
Journal	ACS Omega
Volume Number	7
PubMed Central reference number	PMC9134407
Issue Number	20
PubMed reference number	35647433
e-ISSN	24701343
DOI	10.1021/acsomega.2c01567
Language	English
Publisher	American Chemical Society
Publisher Date	2022-05-12
Access Restriction	Open
Rights License	Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). © 2022 The Authors. Published by American Chemical Society
Content Type	Text
Resource Type	Article
Subject	Chemistry Chemical Engineering