Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane
receptor and pregnane X receptor pathways.
The mission of the company is to apply its proprietary XenoSensor technology, the Steroid Xenobiotic Receptor (SXR), Constitutive Androstane
Receptor (CAR) and the Cytochrome P-450 3A4 (CYP3A4) gene promoter, to improve the safety profiles of existing and developmental medicines.
These androstene and androstane
hormones, designed to restore the biological activity of cellular signaling pathways disrupted by disease and aging, have been demonstrated in humans to possess several properties with potential therapeutic benefit -- they regulate innate and adaptive immunity, reduce nonproductive inflammation and stimulate cell proliferation.
The genes modified by DEHP in PPAR[alpha]-null mice included those involved in xenobiotic metabolism, including targets of constitutive androstane
receptor (CAR) or pregnane X receptor (PXR), and cholesterol biosynthesis which is regulated by other transcription factors, including retinoid X receptor (RXR) (Ren et al.
Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane
In addition to the AHR, Insig1 is regulated by multiple nuclear receptors including PPARa (15 AHR REs), CAR (constitutive androstane
receptor; 2 AHR REs), and PXR (pregnane X receptor).
Regulation of human CYP2C9 by the constitutive androstane
receptor: discovery of a new distal binding site.
In comparison, some non-dioxin-like PCBs such as PCB-153 do not activate AhR but may be constitutive androstane
receptor agonists (Dean et al.
Hepatic CYP2136 expression: gender and ethnic differences and relationship to CYP2136 genotype and CAR (constitutive androstane
Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane
Although our results clearly demonstrate DEHP-mcdiated metabolic interference via PPAR[alpha], other metabolic pathways--such, as those driven by CAR (constitutive androstane
receptor) and Rev-Erb[alpha] (nuclear receptor subfamily 1, group D, member 1)--could also be involved (Eveillard et al.