Table 2.

A nonexhaustive list of OXPHOS inhibitors under study in vivo or in the clinic as anticancer therapeutics

CompoundClinical useComplexIn vivo resultsSelected oncology clinical trialsRef.
MetforminDiabetesIInhibits tumor growth in many tumor types, alleviates hypoxia, and improves IR responseSeveral hundred trials in progress(3, 42, 49)
PhenforminDiabetesITumor growth delay, NSCLC with oncogenic Kras and LKB1 loss, and in MCF7/MDA-MB-231Preclinical(35, 49, 51)
BAY87-2243ExperimentalIAlleviates hypoxia and improves IR response, UT-SCC5 tumorsPhase I, solid tumors, terminated NCT01297530, dose escalation(71, 72)
CAIExperimentalIGrowth delay, LLC tumorsPhase III, NSCLC, completed NCT00003869(63, 64)
ME344ExperimentalIGrowth delay, PyMT spontaneous breastPhase 0, HER2-negative breast, recruiting NCT02806817(65, 66)
FenofibrateHyperlipidemiaIGrowth delay, U87-MG tumors after intercranial deliveryPhase II, myeloma, not recruiting NCT01965834, dose response(67, 68)
LonidamineExperimentalIIGrowth delay in many tumor typesPhase III, breast, completed(61, 76)
α-TOSVitamin E analogueIIInhibits complex II in Chinese Hamster fibroblast tumorsPreclinical(62)
AtovaquoneMalariaIIIAlleviates hypoxia and improves IR response, FaDu tumorsPhase 0, NSCLC, recruiting NCT02628080, 18F-MISO-PET(40, 56, 57)
Arsenic trioxideAPLIVImproves IR response, TLT tumorsClinical use for APL(41, 58)
HydrocortisoneEczemaIVAlleviates hypoxia in FSaII tumors, improves IR responsePreclinical(59, 60)
NOExperimentalIVAlleviates hypoxia in many tumors, improves IR responsePhase II, NSCLC, not yet recruiting NCT01210378(39)
mIBGRadioactive tracerI and IIIAlleviates hypoxia in melanoma, improves IR response under hyperglycemia, R3230 Ac tumorsPreclinical(69, 70)
VLX600ExperimentalI, II, and IVGrowth delay, HT29 tumorsPhase I, solid tumors, recruiting NCT02222363, dose escalation(77)
  • Abbreviations: APL, acute promyelocytic leukemia; αTOS, α-tocopheryl succinate; CAI, carboxyamidotriazole; IR, ionizing radiation; mIBG, meta-iodobenzylguanidine; NO, nitric oxide; TLT, transplantable mouse liver.