Recent advances in non-steroidal FXR antagonists development for therapeutic applications.
Farnesoid X receptor (FXR, NR1H4), a nuclear receptor (NR) highly expressed in the liver, intestine, kidney, adrenal glands and other cholesterol-rich tissues, functions as the master regulator for bile acid homeostasis. FXR, which regulates the expression of genes encoding proteins involved in cholesterol homeostasis, plays an essential role in regulating cholesterol, lipid, and glucose metabolism. Recently, some FXR agonists are reported to have low selectivity on NRs, which forces the researchers to move their eyes onto the development of FXR antagonists with high selectivity. The development of non-steroidal FXR antagonists with different scaffolds including AGN34, tuberatolides, atractylenolides, andrographolides, GW4064 derivatives and 1,3,4-trisubstitutedpyrazolones, provides us a prospect for the therapy of in ammation, metabolic syndrome, diabetes, cholesterol gallstones, and cancer.
Huang
H
Huang
Yong
Y
Xu
Jin
J
Zhu
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. jianli@ecust.edu.cn.
Jian
J
Li
D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy*; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099150:Receptor, Farnesoid X-Activated
D000098:Acetophenones; D004364:Pharmaceutical Preparations; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated