Hepcidinantagonists

Hepcidin antagonists are a class of therapeutic agents designed to counteract the effects of hepcidin. Hepcidin is a peptide hormone produced by the liver that plays a central role in iron metabolism by regulating the absorption of iron from the diet and its release from storage sites. It achieves this by binding to ferroportin, the sole known cellular iron exporter, leading to its degradation. This process reduces the amount of iron entering the bloodstream, thereby lowering serum iron levels.

In conditions where iron overload occurs, such as hereditary hemochromatosis or certain anemias, elevated hepcidin levels contribute to the disease pathology. Conversely, in other conditions, such as anemia of chronic disease, hepcidin is inappropriately high, leading to functional iron deficiency despite adequate or even excessive total body iron stores. Hepcidin antagonists aim to block the action of hepcidin, either by directly inhibiting hepcidin production, preventing its binding to ferroportin, or promoting ferroportin activity.

By reducing hepcidin's inhibitory effect on ferroportin, hepcidin antagonists can increase iron absorption and release from macrophages, thereby increasing serum iron levels and improving iron availability for erythropoiesis. This therapeutic strategy holds promise for treating diseases characterized by iron deficiency due to elevated hepcidin, such as anemia of chronic disease or anemia of inflammation. Research is ongoing to develop safe and effective hepcidin antagonists for clinical use, with several compounds in various stages of preclinical and clinical development.