Emerging Potential Therapeutic Targets of Ferroptosis in Skeletal Diseases

Table 2

Overview of inducers of ferroptosis.

Target	Inducer	Mechanisms associated with ferroptosis
System Xc^-	Erastin	Inhibit system Xc^- activity
	Erastin2	Inhibition of system Xc^- cystine/glutamate transporter
	Imidazole ketone Erastin	Metabolic stabilization inhibitor of system X-
	Glutamate	Inhibit system Xc^- activity
GPX4	RSL3	GPX4 bound to selenocysteine sites
	DPI7 (ML162)	Covalently bind GPX4 (same binding site as RSL3)
	DPI10 (ML210)	Indirectly inhibit GPX4 activity or bind to sites different from RSL3
	Altretamine	Inhibit GPX4 activity
GSH	Buthionine sulfoximine	Reduce GSH synthesis
	N-Acetyl-4-benzoquinone imine	Toxic doses deplete glutathione reserves in the liver
	Cisplatin	Binding to GSH inactivates GXP4
	DPl2	Excessive consumption of GSH
	Piperlongumine	Consume GSH and inhibit GPX4 activity
ROS and iron ions	Heme	Increase of intracellular unstable iron
	Withaferin A	Medium dose upregulated HMOX1 expression and increased intracellular unstable iron. High dose inhibited GPX4 activity
	BAY 11-7085	Upregulation of HMOX1 expression and increase of intracellular unstable iron
	FINO2	Oxidation of Fe^2+ promotes ROS accumulation in cells
	Artesunate	Induce ferritin autophagy and release unstable iron
	Dihydroartemisinin	Induce ferritin autophagy and release unstable iron; binding to free iron inhibits ferritin translation
	Siramesine	Decrease the expression of FPN, increased the expression of transferrin, increased the intracellular unstable iron
	BAY 87-2243	Inhibit mitochondrial respiratory chain complex 1 and increase ROS
	iFSP1	Inhibition of FSP1 inhibits ferroptosis unrelated to glutathione activity
ROS	Auranofin	Inhibit thioredoxin reductase activity
	Statins	Inhibits HMG-COA reductase, which catalyzes rate-limiting steps of the MVA pathway
ROS and GSH	QD-394	Induce lipid peroxidation and decrease GSH/GSSH ratio
ROS and SQS	FIN56	Induce GPX4 degradation. Bind and activate SQS to reduce CoQ10