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

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.

Automated summary

In this study, novel 9,11-seco-cholesterol derivatives were designed and synthesized as FXR antagonists, with compound 9a exhibiting the best FXR antagonistic activity and reducing the expression of FXR target genes.