Table 5.
Drug repurposing candidates for inflammatory diseases targeting NF-κB signaling.
| New Indication | Drug | Original Implication | Effect on NF-κB Signaling | Effect On Inflammation | References |
|---|---|---|---|---|---|
| MS | Imatinib mesylate | Cancer (CML, ALL, GIST, HES, CEL) | Inhibits IκB phosphorylation and DNA binding of NF-κB | Attenuates inflammation and enhances BBB integrity in EAE, Phase II clinical trial for MS | [183,184,185] |
| Clemastine | Relief of allergy symptoms | Decreases NF-κB activity and TLR4 expression | Promotes oligodendrocyte differentiation and remyelination in EAE/MS, inhibits inflammation and microglial M1-like activation | [52,53,55,56,57,58,61] | |
| Ibudilast | Asthma, stroke | Inhibits NF-κB activity (possibly by preventing nuclear translocation) | Reduces inflammation in rats with chronic cerebral reperfusion and MS patients, Phase II clinical trial for MS | [186,187,188,189] | |
| Topotecan | Cancer (ovarian cancer, lung cancer, SCLC) | Inhibits IKKβ and thus IκBα degradation | Attenuates inflammation in EAE | [99] | |
| RA | Ibrutinib | Cancer (MCL, CLL, WM) | Inhibits NF-κB nuclear translocation | Anti-inflammatory effects in models of RA, sepsis and diabetes | [190,191,192,193] |
| Bortezomib | Cancer (MM, MCL) | Proteasome inhibitor, prevents degradation of IκBα | Anti-inflammatory effects in models of MS, RA, lupus erythematosus and colitis, promotes osteoblast activation and RA pathogenesis, Phase II clinical trial for RA | [194,195,196,197,198,199] [200,201] | |
| TDZ | Schizophrenia, psychosis | Inhibits IKKβ phosphorylation and IκBα degradation | Attenuates inflammation in endotoxemia model | [83] | |
| Dasatinib | Cancer (CML, ALL) | Inhibits phosphorylation of IKKα, p65/p100/p105 and c-Rel | Inhibits inflammation and bone erosion in CIA and human FLS, increases IL-10 in CIA | [122,202,203,204] | |
| COVID-19 | Dexamethasone | Inflammatory conditions (RA, asthma, allergies etc.) | Induces the expression of IκBα | Reduces mortality in later stage COVID-19 patients | [205,206,207,208] |
| Anakinra | Relief of RA symptoms | Prevents activation of IL-1R | Reduces hyperinflammation and mortality and improves clinical signs of COVID-19 | [209,210,211,212,213,214] |