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Table 1 Chemotherapeutics that alter cellular redox balance

From: Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side

Compound Status ROS modulation Clinical Trials
Arsenic trioxide (As2O3, trisenox) FDA-approved for the treatment of relapsing AML. ROS:
Inhibits MRC, TrxR and SOD; induces the expression of Nox2 complex genes and depletes Prx III
Phase II study of As2O3 plus decitabine and cytarabine AML with p53 mutations (NCT03381781, not yet recruiting).
Phase I studies of As2O3 plus decitabine (NCT00671697, completed in 2011), plus cytarabine and idarubicin (NCT00093483, completed in 2009) for AML treatment.
Phase II/III study of As2O3 plus altezumab and other chemoteraputic agents for AML or MDS treatment (NCT00454480, completed).
Metformin FDA-approved for the treatment of type 2 diabetes. ROS:
Inhibits mitochondrial ATP production
Phase II study for CLL treatment (NCT01750567, recruiting).
Phase I study of metformin plus ritonavir for relapsed/refractory MM or CLL treatment (NCT02948283, active).
Phase I study for relapsed childhood ALL (NCT01324180; completed).
Phase I study of metformin plus cytarabine for relapsed/refractory AML treatment (NCT01849276, active).
Tigecycline FDA-approved for complicated skin and intra-abdominal infections. ROS:
Inhibits mitochondrial biogenesis
Phase I study for AML treatment (NCT01332786, completed in 2015).
In vitro study of tigecycline in cells from CML patients (NCT02883036, not yet recruiting).
NOV-002 Under clinical trial. ROS:
GSSG mimetic
Phase III study of NOV-002 plus cis-platinum and placlitaxel for NSCLC treatment (NCT00347412, completed in 2010).
2-methoxyestradiol (2-ME, panzem) FDA-approved for ovarian cancer, metastatic malignant melanoma, MM and pancreatic adenocarcinoma. ROS:
SOD inhibitor
Phase II study for the treatment of relapse or plateau phase myeloma (NCT00592579, completed in 2008).
Imexon FDA-approved for pulmonary arterial hypertension, ovarian cancer, multiforme glioblastoma and MM treatment. ROS:
GSH pool depletion
Phase I/II study in MM (NCT00327249, completed in 2008).
Phase II study for the treatment of aggressive lymphomas (NCT01314014, completed in 2014).
ATN-224 Under clinical trial. ROS:
SOD inhibitor
Phase I/II study of ATN-224 plus bortezomib in MM patients (NCT00352742, completed in 2008).
PX-12 Under clinical trial. ROS:
Thioredoxin system inhibitor
Phase I (NCT00736372, completed in 2009) and phase II studies (NCT00417287, completed in 2009) against solid tumours.
Phenethyl isothiocyanate (PEITC) Under clinical trial. ROS:
Export GSH outside of the cell and inhibits GPx
Phase I study for preventing lung cancer (NCT00005883, completed).
PEITC as support care in head and neck cancer patients (NCT03034603, recruiting).
GKT137831 Under clinical trial. ROS:
NOX1 and NOX4 inhibitor
Phase II study for the treatment of patient with type 2 diabetes (NCT02010242, completed in 2015).
Allopurinol FDA-approved for gout treatment and as prophylaxis treatment to prevent chemotherapy-induced uric acid elevation. ROS:
XOD inhibitor
Phase II study of allopurinol in pediatric ALL treatment to improve 6-mercaptopurine treatment (NCT03022747, recruiting).