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Table 6 Small-molecule compounds that induce ferroptosis to inhibit CSCs

From: Emerging agents that target signaling pathways in cancer stem cells

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 [167,168,169]
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]