Your observation that Roxadustat does not reduce PHD expression is consistent with available literature. There is no clear evidence indicating that Roxadustat directly suppresses PHD expression. Instead, Roxadustat primarily functions as a competitive inhibitor of PHD activity, blocking its enzymatic function rather than modulating its protein levels.
Most studies focus on downstream effects, particularly the stabilization of HIF-1α due to PHD inhibition. For example:
PMID: 35729656 demonstrates that PHD inhibition reduces HIF-1α degradation.
PMID: 35597989 (5–25 μM Roxadustat, WB) and PMID: 30817065 (5–10 μM Roxadustat, WB) both report increased HIF-1α levels upon Roxadustat treatment, further supporting its role in inhibiting PHD activity rather than expression.
Thus, Roxadustat’s mechanism primarily involves functional inhibition of PHD enzymes, not transcriptional or translational suppression of PHD genes.
The answer to this question comes from MedChemExpress (MCE) Technical Support.