Factor Inducible by Hypoxia (HIF) Prolyl-Hydroxylase Inhibitors, or HIF-PH inhibitors for short, are a family of pharmaceuticals that have attracted a lot of interest due to their possible medicinal uses. These inhibitors focus on an essential regulatory system that is part of the cellular response to hypoxia, or low oxygen levels. HIF is a transcription factor that, through controlling the expression of genes involved in angiogenesis, erythropoiesis, glucose metabolism, and cell survival, is essential in coordinating the cellular response to hypoxia. Prolyl-hydroxylase enzymes (PHDs) hydroxylate particular proline residues on HIF under normoxic circumstances, designating it for ubiquitin-mediated destruction. On the other hand, PHDs become less active in hypoxic environments, which causes HIF to stabilize, translocate to the nucleus, and then activate target genes. The mechanism of action of HIF-PH inhibitors is to suppress PHD activity, which stops them from hydroxylating HIF. Even in normoxic settings, this inhibition causes HIF to accumulate, simulating the cellular response to hypoxia. Next, the expression of genes that support adaptive reactions to low oxygen levels is induced by the stabilized HIF. Roxadustat is a well-known HIF-PH inhibitor that has been approved for the treatment of anemia brought on by chronic renal disease. Roxadustat treats the underlying causes of anemia by promoting iron utilization and erythropoiesis. Compared to conventional erythropoiesis-stimulating drugs, this innovative therapeutic method has benefits like better response in inflammatory patients and a lower risk of hypertension. Different medical illnesses, such as ischemia diseases, cardiovascular disorders, and neurodegenerative ailments, are being studied in relation to other HIF-PH inhibitors. One intriguing approach to creating therapies that address the underlying causes of these illnesses is to modify the HIF pathway. To maximize the therapeutic potential of HIF-PH inhibitors, however, more study is required due to issues like long-term safety concerns and possible off-target consequences. With the increasing comprehension of cellular oxygen sensing and HIF control, these inhibitors have significant potential to treat a broad spectrum of illnesses linked to hypoxia and abnormal oxygen homeostasis.
