Table 6.

Small-molecule compounds that induce ferroptosis to inhibit CSCs

Name	Target	Mechanism	Type of cancer	Phase	NCT number (starting time)/publication date	Assessment
Salinomycin	Ferroptosis	Increases the production of lipid peroxidation by blocking iron transport and depleting ferritin; these can specifically kill CSCs	Breast cancer	Preclinical	October, 2017	Induces neural and muscular toxicity; changing dosages and making chemical modifications may reduce toxicity [159]
	Ferroptosis	Combined with docetaxel can kill gastric CSCs	Gastric cancer	Preclinical	October, 2017
Ironomycin	Ferroptosis	Reduces the number of CSCs in docetaxel-resistant xenograft models	Breast cancer	Preclinical	February 21, 2020	The potency against CSCs is ten-fold that of salinomycin; may cause nephrotoxicity and hepatotoxicity [160]
Ebselen	Ferroptosis	Targets BCSCs by blocking iron in lysosomes	Breast cancer	Preclinical	February 21, 2020	Induces low toxicity and shows good blood-brain barrier permeability and oral absorption [161]
Substituted pyrazoles					February 21, 2020	Not reported; need studies to prove
Benzylisothioureas					February 21, 2020	Hemoglobinopathy including thalassemia [162]
TMZ and CQ	Ferroptosis	Causes glioblastoma stem cells (GSCs) to die through a form of ferroptosis and reduce the self-renewal ability of GSCs	Glioblastoma	Preclinical	August 6, 2018	TMZ is well tolerated, but may induce hematological toxicity and infection; CQ shows cardiotoxicity [117, 163]
DHA	Ferroptosis	Ferroptosis	Lung, colorectal, and breast cancer cells	Preclinical	January, 2020	Induces neurotoxicity, cardiotoxicity and the toxicity in embryos [164]
	Apoptosis	Inhibits sphere formation and stem marker (CD133, SOX2, and nestin) expression in glioma CSCs	Gliomas	Preclinical	October, 2014
Artesunate	Mitochondrial	Inhibits the stemness of CSCs	Not mentioned	Preclinical	September 2, 2016	Excellently tolerated, and with low adverse effects [165, 166]
	Ferroptosis	Induces cell death through ferroptosis	Pancreatic cancer	Preclinical	May 2, 2015
Ferumoxytol	Ferroptosis	Selectively kills CSCs (A549 and MDA-MB-231 cells)	Lung cancer and breast cancer	Preclinical	August 26, 2013	Well tolerated, but intravenous may cause hypersensitivity, hypotension, and gastrointestinal side effects [167–169]
Sulfasalazine	System Xc−	Inhibits the progression of CSCs overexpressing CD44	Gastrointestinal cancer	Preclinical	March 8, 2011	Induces gastrointestinal toxicity, and combed with other drugs, this side effect may be overcome [170]