TABLE 2.
The mechanisms and research status of typical drugs that target ROS modulators mentioned above.
| Agent | Mechanisms | Status | Clinical trial no. | References |
|---|---|---|---|---|
| Targeting mitochondrial electron transport chain complexes (ETC) | ||||
| Elesclomol | Transport copper ions into cells and cause the oligomerization of lipoylated dihydrolipoamide S‐acetyl‐transferase | Clinical trials phase I/II/III | NCT00522834 a | 335 , 336 |
| MitoQ | Inactivate mitochondrial tumor necrosis factor, target mitochondrial ETC I, III, and IV | Clinical trials phase I/II | NCT06069245 a | 337 , 338 , 339 |
| DT‐010 | Inhibit mitochondrial respiratory chain complex II and the glycolysis pathway, increase DOX accumulation in cells | Preclinical study | – | 340 , 341 |
| Targeting NOXs | ||||
| GKT137831 | Inhibit NOX1, NOX4, and NOX5, downregulate MAPK pathway | Clinical trials phase I/II | NCT03226067 a | 342 , 343 , 344 , 345 |
| NOS31 | Inhibit NOX1, NOX4 | Preclinical study | – | 311 |
| Capsaicin | Inhibit SIRT1/NOX4 signaling pathway, inhibit NAD+‐dependent SIRT1 deacetylase, suppress activated microglia‐derived NADPH oxidase | Clinical trials phase I/II/III | NCT00993070 a | 346 , 347 , 348 , 349 |
| Targeting xCT | ||||
| Erastin | INHIBIT VDAC2/VDAC3, block GSH synthesis, increase lipid peroxidation and lipid ROS | Preclinical study | – | 350 , 351 |
| Sulfasalazine | Regulate CD44v9‐xCT system, inhibit GPX4, trigger ferroptosis | FDA approved | – | 352 , 353 |
| Aspirin | Inhibit xCT, induce ROS‐dependent depolarization and activate voltage‐gated Ca2+ entry | FDA approved | – | 354 , 355 |
| Targeting TrxRs | ||||
| Auranofin | Reduce activity of TrxR1, decrease GSH levels, increase intracellular ROS levels, inhibit the activity of STAT3 and telomerase | FDA approved | – | 330 , 356 , 357 |
| Ethaselen | Inhibit TrxR1 and NF‐κB, increase ratio of Bax to B cell lympoma‐2 protein | Preclinical study | – | 333 , 358 |
| Ruthenium(II) complex | Induce the potential loss of mitochondria membrane, inhibit TrxR activity, promote oxidative stress‐sensitive MAPK | Preclinical study | – | 359 , 360 , 361 |
Abbreviations: DOX, doxorubicin; GSH, glutathione; MAPK, mitogen activated protein kinase; NOXs, nicotinamide adenine dinucleotide phosphate oxidases; NADPH, nicotinamide adenine dinucleotide phosphate; SIRT1, sirtuin1; STAT3, signal transducer and activator of transcription 3; TrxRs, thioredoxin reductases; VDAC, voltage‐dependent anion channel; xCT, the glutamate/cystine antiporter solute carrier family 7 member 11 (SLC7A11); clinical trials are available from: http://ClinicalTrials.gov/.
a
Trials with reported results.