Hypoxia Inducible Factor Stabilization As a Novel Strategy to Treat Anemia

S.      Zhao; J.      Wu

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.

Keywords: Anemia, FIH inhibitors, HIF-PH pathway, iron chelators, natural products, PHD2 inhibitors, von Hippel–Lindau protein.

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