4-(2-(2-chloro-4-((5-cyclopropyl-3-(2-6-dichlorophenyl)-4-isoxazolyl)methoxy)phenyl)cyclopropyl)benzoic-acid and Hypertension--Portal

Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study.. PX decreased portal pressure in non-cirrhotic PPVL (12.6±1.7 vs. 10.4±1.1mmHg; p=0.020) and cirrhotic CCl. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction.. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut.

Topics: Animals; Benzoates; Bile Acids and Salts; Bilirubin; Capillaries; Cholesterol; Disease Models, Animal; Hypertension, Portal; Isoxazoles; Male; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Rats; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear; Vascular Remodeling; Vascular Resistance