Table 2.
Examples of activity-based drug repositioning for anticancer applications.
| Drugs | Original uses | Proposed anticancer mechanisms | Developmental status |
|---|---|---|---|
| Itraconazole | * Treatment for fungal infections | * Inhibiting endothelial cell cholesterol trafficking and angiogenesis 18, 25 * Inhibiting Hedgehog pathway 19 |
Phase I and II |
| Nelfinavir | * Treatment for HIV infections | * Inhibiting 20S proteasome and AKT signaling 38, 39 * Inhibiting HSP90 and HER2 signaling 36, 41 * Inducing ER stress and autophagy, and inhibiting angiogenesis 32, 42, 43 |
Phase I and II |
| Digoxin | * Treatment for cardiac diseases | * Inhibiting Na+/K+-ATPase 63 * Acting as a phytoestrogen and inhibiting androgen receptor signaling 59, 61 * Inhibiting HIF-1α synthesis 62 |
Phase I and II |
| Nitroxoline | * Treatment for urinary tract infections | * Inhibiting human MetAP2 and sirtuins in endothelial cells 67 * Inducing premature senescence and inhibiting angiogenesis 67 * Inhibiting cathepsin B 69 |
Preclinical trials |
| Riluzole | * Treatment for Amyotropic lateral sclerosis |
* Inhibiting the release of glutamate 72 * Inhibiting cell proliferation of metabotropic glutamate receptor 1 (GRM1)-expressing human melanoma cells 72 |
Phase I and II |
| Mycophenolic acid | * Immunosuppressant | * Inhibiting type-1 inosine monophosphate dehydrogenase (IMPDH-1) and angiogenesis 73 * Inhibiting c-Myc signaling network in endothelium 74 |
Phase I |
| Disulfiram | * Treatment for chronic alcoholism | * Inhibiting proteasome when complexed with metals 75 * Inhibiting DNA methyltransferase 1 (DNMT1) 76 |
Phase II and III |