AZ876 is a novel high-affinity LXR agonist. AZ876 was 25-fold and 2.5-fold more potent than GW3965 on human (h)LXRα and hLXRβ respectively.(1) AZ876 suppressed up-regulation of hypertrophy- and fibrosis-related genes, and further inhibited prohypertrophic and profibrotic transforming growth factor β (TGFβ)-Smad2/3 signalling.(2) AZ876 prevented TGFβ- and angiotensin II-induced fibroblast collagen synthesis, and inhibited up-regulation of the myofibroblastic marker, α-smooth muscle actin.(3) The reference for administration is 20 umol/kg/day in vivo.
[1]. Cannon MV et al. The liver X receptor agonist AZ876 protects against pathological cardiac hypertrophy and fibrosis without lipogenic side effects. Eur J Heart Fail. 2015 Mar;17(3):273-82. [2]. van der Hoorn J et al. Low dose of the liver X receptor agonist, AZ876, reduces atherosclerosis in APOE*3Leiden mice without affecting liver or plasma triglyceride levels. Br J Pharmacol. 2011 Apr;162(7):1553-63.