Description
TCPOBOP (76150-91-9) is an activator of the mouse constitutive androstane receptor (mCAR) and human Preganane X receptor.1 Tumor promoter of mouse hepatocarcinogenesis.
Uses
TCPOBOP is an agonist for mCAR, inducing cytochrome P450 monooxygenases and multidrug resistance and cenobiotic efflux proteins.
General Description
A highly potent inducer of phenobarbital-like class of cytochrome P450 (CYP) enzymes. A tumor promoter that induces hepatocyte proliferation, independent of the presence of cytokines or transcription factors. Activates orphan nuclear receptors mCAR (mouse constitutive androstane receptor) and hPXR (human pregane X receptor), but has little or no effect on hCAR and mPXR. Also suppresses the expression of multi-drug resistance genes
mdr2 and
mdr3 in mouse liver.
Biochem/physiol Actions
TCPOBOP enhances the nuclear receptor CAR transactivation of cytochrome P450 (CYP), as dose-dependent direct agonist of CAR. The most potent known member of the phenobarbital-like class of CYP-inducing agents.
References
1) Tzameli et al. (2000) The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR; Mol. Cell. Biol., 20 2951
2) Diwan et al. (1992) Tumor-promoting and hepatocarcinogenic effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in DBA/2NCr and C57BL/6NCr mice and an apparent promoting effect on nasal cavity tumors but not on hepatocellular tumors in F344/NCr rats initiated with N-nitrosodiethylamine; Carcinogenesis, 13 1893
