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

[Image: see text] 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-ch...

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Autores principales: Zhou, Jia-Xu, Li, Cui-Na, Liu, Ya-Meng, Lin, Su-Qin, Wang, Ying, Xie, Cen, Nan, Fa-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134407/
https://www.ncbi.nlm.nih.gov/pubmed/35647433
http://dx.doi.org/10.1021/acsomega.2c01567
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author Zhou, Jia-Xu
Li, Cui-Na
Liu, Ya-Meng
Lin, Su-Qin
Wang, Ying
Xie, Cen
Nan, Fa-Jun
author_facet Zhou, Jia-Xu
Li, Cui-Na
Liu, Ya-Meng
Lin, Su-Qin
Wang, Ying
Xie, Cen
Nan, Fa-Jun
author_sort Zhou, Jia-Xu
collection PubMed
description [Image: see text] 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 (IC(50) = 4.6 μM) and decreased the expression of the target genes of FXR in vivo.
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spelling pubmed-91344072022-05-27 Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists Zhou, Jia-Xu Li, Cui-Na Liu, Ya-Meng Lin, Su-Qin Wang, Ying Xie, Cen Nan, Fa-Jun ACS Omega [Image: see text] 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 (IC(50) = 4.6 μM) and decreased the expression of the target genes of FXR in vivo. American Chemical Society 2022-05-12 /pmc/articles/PMC9134407/ /pubmed/35647433 http://dx.doi.org/10.1021/acsomega.2c01567 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/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/).
spellingShingle Zhou, Jia-Xu
Li, Cui-Na
Liu, Ya-Meng
Lin, Su-Qin
Wang, Ying
Xie, Cen
Nan, Fa-Jun
Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists
title Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists
title_full Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists
title_fullStr Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists
title_full_unstemmed Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists
title_short Discovery of 9,11-Seco-Cholesterol Derivatives as Novel FXR Antagonists
title_sort discovery of 9,11-seco-cholesterol derivatives as novel fxr antagonists
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134407/
https://www.ncbi.nlm.nih.gov/pubmed/35647433
http://dx.doi.org/10.1021/acsomega.2c01567
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