Table 1.

Mitochondrial targets of anticancer agents.

Biological process	Mitochondrial Target	Drug name	Level of evidence
TCA cycle enzymes	PDH and KGDHC inhibitor	CPI-613 (Devimistat)	•Failed phase III clinical trial in pancreatic cancer •Failed acute clinical trial in myeloid leukemia in combination with chemotherapy •Current clinical trial in pancreatic cancer in combination with chemoradiation
	IDH inhibitor	AG-221and AG-881	•Current clinical trial in acute myelogenous leukemia carrying IDH mutations
	IDH inhibitor	AGI-5198	•Preclinical anti-cancer effects in vivo
Metabolite transporters	MPC inhibitor	UK-5099	•Current clinical trial
	HSP90 inhibitor	Gamitrinib	•Preclinical safety and anti-cancer effects in vivo •Current phase I clinical trial
OXPHOS/ET	Complex II inhibitor Uncoupler	Sorafenib	•FDA-approved anti-cancer therapy
	Complex I and ATP synthase	Tamoxifen	•FDA-approved anti-cancer therapy
	Complex I inhibitor	Metformin	•Failed phase III clinical trial in breast cancer •Current clinical trials for colorectal, breast and prostate ccancer
	Complex I inhibitor	IACS-010759	•Failed phase I clinical trials in acute myeloid leukemia and solid tumors
	Complex II inhibitor	α-tocopherol succinate	•Anti-cancer effects in vitro
	Iron chelator that inhibits complexes I, II, and IV	VLX600	•Successful phase I trial in advanced solid tumors
	Methylation-controlled J protein that negatively regulates complex I	MCJ mimetics (MITOx20, MITOx30)	•Anti-cancer effects in vitro
	Uncoupler	NEN	•Failed clinical trial in prostate cancer •Terminated clinical trial in colon cancer due to low accrual •Current clinical trial in prostate cancer •Reformulated compound, successful phase 1b trial
	Uncoupler	Nitazoxanide	•Preclinical safety and anti-cancer effects in vivo
	Uncoupler DNA topoisomerase II inhibitor	Ellipticine and derivatives	•Failed phase II clinical trial
	Uncoupler	CRMP	•Preclinical anti-cancer effects in vivo
	Uncoupler	BAM15	•Preclinical anti-cancer effects in vivo
	Uncoupler	SR4	•Preclinical anti-cancer effects in vivo
	Uncoupler	FR58P1a	•Anti-cancer effects in vitro
	Uncoupler Tyrosine kinase inhibitor	Tyrphositn A9	•Anti-cancer effects in vitro
	Uncoupler EAPC inhibitor	ESI-09	•Anti-cancer effects in vitro
Antioxidants	Blocks GSH synthesis	Buthionine sulfoximine	•Successful phase I clinical trial in neuroblastoma
	Trx inhibitor	PX-12	•Terminated phase II clinical trial in pancreatic cancer
	GPD2-dependent ROS formation inhibitor	KM04416	•Anti-cancer effects in vitro