Table 2.
Pharmacologic targeting of metabolic pathways in the rheumatic diseasesa
| Drug | Mechanism of action | Molecular target | Disease |
|---|---|---|---|
| Methotrexate | Purine metabolism | DHFR | RA, PsA |
| Azathioprine | Guanine metabolism | TPMT/PRT | RA |
| Mycophenolate | Guanine synthesis | IMPDH | SLE |
| Leflunomide | Pyrimidine metabolism | DHODH | RA |
| Apremilast | PKA | PDE4 | PsA |
| Hydroxychloroquine | Autophagy | Lysosomal ATPase | RA, SLE, PsA |
| Corticosteroid | Glycolysis, autophagy | GCR | SLE, RA, PsA |
| Rapamycin | Autophagy | mTORC1 | SLE, lupus nephritis, SSc, RA/JRA, SS |
| Everolimus | Autophagy | mTORC1 | PH |
| OSI‐027 | ATP‐competitive | mTORC1/mTORC2 | SSc, RA |
| NAC | Antioxidant | GSH | SLE, RA/CIA, SS, ILD |
| Metformin | Antioxidant | ETC complex I | SLE, CIA |
| Fingolimod | Receptor modulator | S1P receptor | SLE, RA, MS, IBD |
| DHS1P | S1P antagonist | PTEN | SSc |
| PAT‐048 | Autotaxin inhibitor | LPA synthesis | SSc |
Literature references are listed in Supplementary Table 1 (available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/doi/10.1002/art.40223/abstract). DHFR = dihydrofolate reductase; RA = rheumatoid arthritis; PsA = psoriatic arthritis; TPMT/PRT = thiopurine methyltransferase/phosphoribosyltransferase; IMPDH = inosine monophosphate dehydrogenase; SLE = systemic lupus erythematosus; DHODH = dihydroorotate dehydrogenase; PKA = protein kinase A; PDE4 = phosphodiesterase 4; GCR = glucocorticoid receptor; mTORC1 = mechanistic target of rapamycin complex 1; SSc = systemic sclerosis; JRA = juvenile RA; SS = Sjögren's syndrome; PH = pulmonary hypertension; GSH = glutathione; ILD = interstitial lung disease; ETC = electron transport chain; CIA = type II collagen–induced arthritis; S1P = sphingosine‐1‐phosphate; MS = multiple sclerosis; IBD = inflammatory bowel disease; LPA = lysophosphatidic acid.