Table 2.
Drugs Targeting Redox Systems for the Treatment of Cancer
| Drug | Target | Clinical activity | Statusa |
|---|---|---|---|
| Aurofin | Thioredoxin reductase | Ongoing trials |
NCT02089048 NCT01419691 I NCT01737502 I |
| Motexafin gadolinium | Thioredoxin reductase, ribonucleotide reductase | Radio/chemosensitizer | Not approved by FDA |
| Motexafin lutetium | Apoptosis | Photosensitization | No longer being developed |
| PX-12 | Thioredoxin, HIF-1 | Stable disease | Iv use no longer pursued |
| Arsenic trioxide | Mitochondria, Trx-1/-2,GSH | FDA approved for APL |
NCT00275067 NCT00661544 NCT00258245 |
| Buthionine sulfoximine | γ-glutamylcysteine ligase (GSH) | Chemosensitizer no clinical advantage |
No longer being developed |
| Telcyta (TLK-286) | Glutathione S-transferase -ρi | Chemosensitizer no clinical advantage |
Development status unknown |
| Telintra (TLK199) | Glutathione S-transferase -pi | Chemosensitizer | Development status unknown |
| Disulfiram | Acetaldehyde dehydrogenase, GSH/GSSG | Chemosensitizer no clinical advantage |
No longer being developed |
| NOV-002 | γ-glutamyl-transpeptidase, GSH/GSSG | Chemosensitizer no clinical advantage |
No longer being developed |
| N-acetylcysteine | GSH prodrug | Decrease side effects, no clinical advantage |
NCT02241876, |
| PX-478 | HIF-1 | Phase I trial only | Not currently being developed |
| EZN-2968 | HIF-1 | Lowers HIF-1 | NCT02564614 |
| BAY 87-2243 | HIF-1/2, mitochondrial complex-1 | Toxic at doses used | development status unknown |
| Topotecan | topoisomerase I (HIF-1) | Trend to lower HIF-1, a partial tumor response | FDA-approved drug, development status as HIF-1 inhibitor unknown |
| EZN-2208 | Topoisomerase I (HIF-1) | HIF-1 activity unknown, no clinical survival advantage | Company not developing clinical products |
| Bortezomib | Proteasome (NF-κB) | Significant clinical activity, not known if NF-κB related |
FDA-approved drug |
| Fenretinide | Retinoic acid receptor agonist, increases ROS | Induces apoptosis, not known if activity related to ROS |
NCT01535157 NCT00646230 |
| α-Tocopherol | Free radical scavenger | Large-scale clinical cancer prevention trials show no clinical benefit | NCT02397486 |
| Vitamin C | Free radical scavenger, H2O2 prodrug | No convincing evidence of clinical benefit | Development of high-dose iv vitamin C continues |
| Curcumin | Free radical scavenger | No convincing evidence of clinical advantage | Development of more bioavailable forms continues |
a
Refers to an ongoing clinical trial from the NIH Clinical Trials database at ClinicalTrials.gov.
APL, acute promyelocytic leukemia; FDA, Food and Drug Administration; GSH, glutathione; GSSG, oxidized glutathione; ROS, reactive oxygen species.