Kodama, Susumu published the artcileAssociation between in vitro nuclear receptor-activating profiles of chemical compounds and their in vivo hepatotoxicity in rats, Application In Synthesis of 637-07-0, the publication is Journal of Toxicological Sciences (2021), 46(12), 569-587, database is CAplus.
The liver plays critical roles to maintain homeostasis of living organisms and is also a major target organ of chem. toxicity. Meanwhile, nuclear receptors (NRs) are known to regulate major liver functions and also as a critical target for hepatotoxic compounds In this study, we established mammalian one-hybrid assay systems for five rat-derived NRs, namely PXR, PPARα, LXRα, FXR and RXRα, and evaluated a total of 326 compounds for their NR-activating profiles. Then, we assessed the association between their NR-activating profile and hepatotoxic endpoints in repeated-dose toxicity data of male rats from Hazard Evaluation Support System. In the in vitro cell-based assays, 68, 38, 20, 17 and 17 compounds were identified as positives for PXR, PPARα, LXRα, FXR and RXRα, resp. The association analyses demonstrated that the PXR-pos. compounds showed high frequency of endpoints related to liver hypertrophy, such as centrilobular hepatocellular hypertrophy, suggesting that PXR activation is involved in chem.-induced liver hypertrophy in rats. It is intriguing to note that the PXR-pos. compounds also showed statistically significant associations with both prolonged activated partial thromboplastin time and prolonged prothrombin time, suggesting a possible involvement of PXR in the regulation of blood clotting factors. Collectively, our approach may be useful for discovering new functions of NRs as well as understanding the complex mechanism for hepatotoxicity caused by chem. compounds
Journal of Toxicological Sciences published new progress about 637-07-0. 637-07-0 belongs to chlorides-buliding-blocks, auxiliary class Inhibitor,Cell Cycle,PPAR, name is Ethyl 2-(4-chlorophenoxy)-2-methylpropanoate, and the molecular formula is C12H15ClO3, Application In Synthesis of 637-07-0.
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