Table 2.

Overview of Drugs that Target Redox Platforms

Drug	Mechanism of Action	Notes	Reference
Amifostine	aminothiol used to protect normal tissues against radiation toxicities	FDA approved in esophageal cancer	Shen et al. (2001)
MESNA	thiol used with alkylating agents to protect bladder	as an adjuvant, reduces incidence of hemorrhagic cystitis	Verschraagen et al. (2003)
NOV-002	mimetic of GSSG; designed to interfere with cancer cell GSH homeostasis while protecting bone marrow	negative results in phase 3 clinical trials	Townsend et al. (2008)
Buthionine sulfoximine	inhibitor of de novo GSH biosynthesis	phase 1/2 clinical trials showed dose-limiting liver toxicity	O’Dwyer et al. (1992)
Sulforaphane	organosulfur isothiocyanate with reported chemoprevention properties	tested in a variety of preclinical and clinical settings	Hail et al. (2008)
Arsenic trioxide	crosslinks vicinal thiols in sensitive proteins	FDA approved in promyelocytic leukemia	Wang and Chen (2008)
Auranofin	non-specific binding, but inhibits thioredoxin reductase	plausible use in ovarian cancer	Fan et al. (2014a)
PX-12	irreversible inhibitor of thioredoxin-1	following drug administration, patients experienced strong, dose-limiting sulfurous odors	Baker et al. (2006)
Telcyta	Alkylating prodrug activated by GSTP	Negative results phase 3 clinical trials	Tew (2005)
Telintra	small-molecule inhibitor of GSTP	clinical benefit in myelodysplastic syndrome patients	Ruscoe et al. (2001)
Ethacrynic acid	Michael addition chemistry reacts with thiols	FDA approved as a diuretic; used in combination with alkylating agents; dose-limiting fluid imbalance in cancer patients	O’Dwyer et al. (1991)
PRIMA-1 or APR-246	Michael addition chemistry with apparent specificity toward p53	restores wild-type functions of p53; testing in progress	Ogiwara et al. (2019)
Erastin	small-molecule modulator of voltage-dependent anion channels and inhibitor of Gpx4	analog development leads to phase 1 study of PRLX 93936	Yang et al. (2014)
Ascorbate	high doses cause high H2O2 and deplete GSH and NADPH	numerous phase 1/2 trials but as yet, no consensus on efficacy	Chen et al. (2005)
CB-839	inhibits glutaminase 1 (GLS1), limits glutamine, reduces glutamate and cysteine	evidence of cancer specificity based on salvage pathways; ongoing phase 1/2 trials in combinations	Romero et al. (2017)
Ivosidenib (AG-120)	inhibits mutant IDH1 variants with concomitant depletion of NADPH and GSH pools	numerous phase 1/2 trials; phase 3 with azacytidine in AML	Popovici-Muller et al. (2018)