Table 2.

Hepcidin antagonists.

Mechanism of action	Drug	Target	Evidence	Clinical stage	Ref.	Implicated disorders
	SOSTDC1	BMP pathway	Cell culture	Preclinical	[14]	Anemia of chronic disease; iron refractory iron-deficient anemia
	Heparins	BMP pathway	Cell culture, animal models, patients	FDA-approved anti-coagulant	[59,86–90]
	sHJV.Fc (FMX-8)	BMP pathway	Cell culture and animal models	Clinical trials terminated	[43,56,58,67,91,92]
	Dorsomorphin\LDN-193189	BMP pathway	Cell culture and animal models	Preclinical; orphan drug designation	[58,93–97]
	TP-0184	BMP pathway	Cell culture and animal models	Preclinical	[57,98]
	ABT-207	BMP pathway	Animal models including nonhuman primates	Preclinical	[99]
	h5F9-AM8	BMP pathway	Animal models	Preclinical	[99]
	XEN701	BMP pathway	None	Preclinical/discontinued	[100,101]
Inhibit positive regulators	siHJV	BMP pathway	Cell culture and animal models	Preclinical	[102]
	siTFR2	Iron-sensing/BMP pathway	Cell culture and animal models	Preclinical	[102]
	Siltuximab (Slyvant™)	IL-6 pathway	Patients	FDA approved for MCDa	[103–105]
	Tocilizumab (ACTEMRA®)	IL-6 pathway	Patients	FDA approved for RA and JIAb	[106–108]
	AG490	IL-6 pathway	Cell culture and animal models	Preclinical	[109–112]
	PpYLKTK	IL-6 pathway	Cell culture	Preclinical	[110,111]
	Curcumin	IL-6 pathway	Cell culture and animal models	Phase 1/2/3/4 for several indications	[111,113–115]
	3,3′-Diindolyl-methane	IL-6 pathway	Rainbow trout model	Phase 1/2/3 for several indications	[116,117]
	Infliximab (REMICADE®)	TNFα/IL-6 pathway	Cell culture and patients	FDA-approved	[107]
Enhance negative regulators	Erythroferrone	Erythroferrone	Cell culture and animal models	Preclinical	[23,118,119,120]
	siHepcidin	Hepcidin	Cell culture and animal models	Preclinical	[102]
	12B9m	Hepcidin	Cell culture and animal models including nonhuman primates	Preclinical	[121]
Disrupt hepcidin–ferroportin (FPN) interaction	PRS-080	Hepcidin	Cell culture and animal models	Phase 1	[122–124]
	NOX-H94 (Lexaptepid Pegol)	Hepcidin	Cell culture, nonhuman primates, patients	Phase 2	[125–129]
	LY2787106	Hepcidin	None	Preclinical/discontinued	[130,131]
	LY2928057	FPN	Nonhuman primates	Phase 1	[132,133]
	Fursultiamine	FPN	Cell culture	Preclinical	[134]

^aMulticentric Castleman’s Disease (MCD).

^bRheumatoid (RA) and juvenile idiopathic arthritis (JIA).