1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and related compounds as inducers of hepatic monooxygenases: Structure-activity effects
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Transcript and protein marker patterns for the identification of steatotic compounds in human HepaRG cells
2020, Food and Chemical ToxicologyCitation Excerpt :Pronounced species differences have been described regarding the ligand spectra and downstream effects of steatosis-related nuclear receptors such as the constitutive androstane receptor (CAR), the pregnane-X-receptor (PXR), and the peroxisome proliferator-activated receptor α (PPARα). Murine CAR, for example, is strongly activated by the model agonist TCPOBOP (1,4-Bis [2-(3,5-dichloropyridyloxy)]benzene) (Kelley et al., 1985; Tzameli et al., 2000), whereas the compound is not a good activator of the human receptor (Honkakoski et al., 2003). Similarly, the fungicide and CAR activator cyproconazole is more potent at the murine receptor (Marx-Stoelting et al., 2017), whereas in human cells the compound appears to rather activate PXR (Luckert et al., 2018).
The CAR agonist TCPOBOP inhibits lipogenesis and promotes fibrosis in the mammary gland of adolescent female mice
2018, Toxicology LettersCitation Excerpt :Intriguingly, TC was a remarkably potent species-selective inducer of CYP450 in mice but not in rats. In vitro, TC induced both nuclear localization and CYP2B10 expression in primary hepatocytes (Kelley et al., 1985). TC activation of CAR mediated specific xenobiotic induction of drug metabolism and enhanced acetaminophen-induced hepatotoxicity (Wei et al., 2000; Zhang et al., 2002).
Creation and preliminary characterization of pregnane X receptor and constitutive androstane receptor knockout rats
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