CAR agonist 39 is a potent, selective nuclear constitutive androstane receptor (CAR, NR1I3) agonist with EC50 of 611 nM in TR-FRET assays and EC50 of 1.22 uM in CAR LBD assembly assays.
CAR agonist 39 shows no activity to activate PXR at 10 μM.
CAR agonist 39 (1 uM) could significantly upregulate CYP2B6 mRNA in primary human hepatocyte models, significantly decreases the number of cells with specific cytoplasm EGFP-hCAR + Ala localization.
CAR agonist 39 is a active ligand for all CAR variants, displays significant activity in the induction experiments in PHH and HepaRG cells irrespective of their lower affinities to wtCAR or CAR3 variants in CAR TR-FRET and cellular assays.
CAR agonist 39 regulates CAR target genes in humanized CAR mice as well as human hepatocytes, it does not activate other nuclear receptors and is nontoxic in cellular and genotoxic assays as well as in rodent toxicity studies.