Hepcidin and HFE protein: Iron metabolism as a target for the anemia of chronic kidney disease

Table 1 A list of anti-hepcidin therapies evaluated in experimental models or under pre-clinical development

Drug	Ref.	Mechanism of action	Experimental model	Effects
Anti-hepcidin Abs	[65]	Direct inhibition of hepcidin	Mouse model of ACD	Increased sensitivity to Epo
Anti BMP6 Abs	[68]	Inhibition of BMP-6 signaling	Mice	Decrease hepcidin Increase serum iron and transferrin saturation
Dorsomorphin	[66]	Inhibition of BMP type 1 receptor kinase function	Cultured mouse pulmonary artery smooth muscle cells Hepatocytes Zebrafish Mice	Decrease hepcidin Increase serum iron
Soluble HJV	[55]	Decoy receptor for BMP-6 (competition of membrane HJV and soluble HJV for BMP binding) Inhibition of BMP signaling	Hepatoma-derived HepG2 cells Mice	Decrease hepcidin Increased ferroportin expression Increase serum iron and transferrin saturation Mobilize reticuloendothelial cell iron stores
Heparins	[69]	BMP-6 sequestration and consequent inhibition of BMP-6 signaling	Hepatoma-derived HepG2 cells Mice	Decrease hepcidin Increase serum iron Reduce spleen iron concentration
Epo	[67]	Increase HIF signaling, direct effect?	Mouse hepatocytes Hepatoma-derived HepG2 cells	Decrease hepcidin
Spiegelmers	[71]	Bind and neutralise hepcidin biological activity	Mouse macrophages Mice Cynomolgus monkeys	Inhibition of hepcidin-induced ferroportin degradation Inhibition of hepcidin-induced hypoferremia
Anticalins	[72]	Encapsulate and neutralise hepcidin biological activity	Cell system Mice Monkeys	Inhibition of hepcidin-induced ferroportin degradation Inhibition of hepcidin-induced hypoferremia

Abs: Antibodies; ACD: Anemia of chronic diseases; HJV: Hemojuvelin.