Downregulation of CYP1A2, CYP2B6, and CYP3A4 in human hepatocytes by prolyl hydroxylase domain 2 inhibitors via hypoxia-inducible factor-α stabilization was written by Takano, Hiroki;Yamaguchi, Jun-ichi;Kato, Sota;Hamada, Makoto;Tada, Mika;Endo, Hiromi. And the article was included in Drug Metabolism & Disposition in 2021.Quality Control of Methyl 6-Cyanopyridine-3-carboxylate This article mentions the following:
Hypoxia-inducible factor (HIF) is associated with the expression of CYP, but the underlying mechanism remains uncertain. In this study, we investigated the effect of HIF-α stabilization caused by novel prolyl hydroxylase domain (PHD) 2 inhibitors, which are HIF-α stabilizers that mimic hypoxia, on the expressions of CYP1A2, CYP2B6, and CYP3A4 in human hepatocytes. An mRNA expression anal. of human hepatocytes treated with PHD2 inhibitors for 72 h showed the downregulation of genes encoding CYP1A2, CYP2B6, and CYP3A4. The mRNA repressions were accompanied with an increase in erythropoietin protein, a marker of HIF-α stabilization, indicating that HIF-α stabilization was involved in the downregulation of the CYP isoforms. To understand the underlying mechanisms, we assessed the relationship between the expressions of the CYP isoforms and those of their regulating transcription factors [aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT), constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoid X receptor (RXR)] in human hepatocytes treated with the HIF-α stabilizers. As a result, the mRNA level of AhR did not decrease, although ARNT expression was repressed. On the other hand, the mRNA expression levels of CAR, PXR, and RXR were repressed and closely associated with those of CYP2B6 and CYP3A4. Although the underlying mechanism of the downregulation for CYP1A2 remains unclear, the presently reported results suggest that the downregulation of CYP2B6 and CYP3A4 via HIF-α stabilization is caused by a decrease in the expressions of CAR, PXR, and RXR. In the experiment, the researchers used many compounds, for example, Methyl 6-Cyanopyridine-3-carboxylate (cas: 89809-65-4Quality Control of Methyl 6-Cyanopyridine-3-carboxylate).
Methyl 6-Cyanopyridine-3-carboxylate (cas: 89809-65-4) belongs to pyridine derivatives. Pyridine is diamagnetic and has a diamagnetic susceptibility of â?8.7 à 10â? cm3·molâ?.The molecular electric dipole moment is 2.2 debyes. The standard enthalpy of formation is 100.2 kJ·molâ? in the liquid phase and 140.4 kJ·molâ? in the gas phase. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Quality Control of Methyl 6-Cyanopyridine-3-carboxylate