Title:Hypoxia Inducible Factor Stabilization As a Novel Strategy to Treat Anemia
Volume: 20
Issue: 21
Author(s): S. Zhao and J. Wu
Affiliation:
Keywords:
Anemia, FIH inhibitors, HIF-PH pathway, iron chelators, natural products, PHD2 inhibitors, von Hippel–Lindau
protein.
Abstract: Anemia, one of the most common blood disorders, globally affecting ~1.62 billion people, occurs when the
level of healthy red blood cells (RBCs) or/and hemoglobin in the body becomes too low. It can cause a variety of complications
to human body, some of which are potentially very serious and carry significant risk factors, thus representing a
big burden for social and economic development. Current therapeutic methods are efficient in controlling this disease but
associated with many problematic issues. One way to circumvent these issues is by targeting HIF-PH (Hypoxia inducible
factor prolyl hydroxylases) pathway. HIF is an oxygen-sensitive transcription factor that enables aerobic organisms to
adapt to hypoxia through the transcriptional activation of up to 200 genes, many of which are critical to cell survival. Experimental
and clinical studies have demonstrated that stabilization of HIF can up-regulate erythropoietin (EPO) expression
and in turn increase count of RBCs potentially without causing drug resistance and cardiovascular diseases commonly
seen with other therapies, rendering HIF stabilization a promising way to treat anemia. In this review, we highlight
the biology of HIF-PH pathway, as well as the recent advances of HIF stabilizers of a natural or synthetic origin and concerns
regarding drug development in this field.
