1383816-45-2Relevant academic research and scientific papers
Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH)
Tully, David C.,Rucker, Paul V.,Chianelli, Donatella,Williams, Jennifer,Vidal, Agnès,Alper, Phil B.,Mutnick, Daniel,Bursulaya, Badry,Schmeits, James,Wu, Xiangdong,Bao, Dingjiu,Zoll, Jocelyn,Kim, Young,Groessl, Todd,McNamara, Peter,Seidel, H. Martin,Molteni, Valentina,Liu, Bo,Phimister, Andrew,Joseph, Sean B.,Laffitte, Bryan
, p. 9960 - 9973 (2018/01/11)
The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and nonalcoholic steatohepatitis. We identified a novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted isoxazole scaffold. Herein, we report the discovery of 1 (tropifexor, LJN452), a novel and highly potent agonist of FXR. Potent in vivo activity was demonstrated in rodent PD models by measuring the induction of FXR target genes in various tissues. Tropifexor has advanced into phase 2 human clinical trials in patients with NASH and PBC.
COMPOSITIONS AND METHODS FOR MODULATING FXR
-
Page/Page column 131; 133, (2012/07/13)
The present invention relates to compounds of Formula (I), a stereoisomer, enantiomer, a pharmaceutically acceptable salt or an amino acid conjugate thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesiod X receptors (FXR).
