Table 1.
Inhibitors of the metabolic pathways, their influence on Treg cells and disease applied.
| Related Mechanism Pathways | Drugs | Pharmacological Effects | Influence on Treg Cells | Other biological Functions | Experimental Subject | Associated Disease | Reference |
|---|---|---|---|---|---|---|---|
| carbohydrate metabolism | CG-5 | Decrease Glut1 expression | Increase Treg cells differentiation | In vitro: block glycolysis in CD4+ T cells | Lupus-prone mouse model | SLE | (220) |
| 2-DG | Compete with glucose in binding to HKII to inhibit cellular glycolysis activity and regulate the glycolytic pathway | Induce Treg cells differentiation and suppression | In vivo: dampen Th1 and Th17 cells development | Lewis rats | GBS | (221) | |
| Decreased ECAR and OCR in TC CD4+ T cells | TC mice | SLE | (210) | ||||
| DCA | Inhibit the dephosphorylation and deactivation of PDC to keep PDC active | Increase Treg cells expansion | Inhibit Th17 cells survival and proliferation | C57BL/6J mice | EAE | (222, 223) | |
| Metho- trexate |
Act by competitive inhibition of dihydrofolate reductase to deplete One-carbon metabolism | Increase Treg cells expansion | Deplete purine biosynthesis enzymes | Patients with RA and healthy controls | RA | (224) | |
| Lipid metabolism | Piogli- tazone |
Activate PPARγ and high affinity binding to the PPARγ ligand-binding | Induce VAT Treg cells | Decrease the elevated serum levels of both creatinine and CK-MB | C57Bl/6 mice | Obesity | (225, 226) |
| Sora-phen A | Lower cellular malonyl CoA, attenuate DNL and the formation of fatty acid elongation products derived from exogenous fatty acids | Induce Treg cells differentiation | In vivo: inhibit TH17 cell–associated inflammatory diseases | TACC1 mice | EAE | (211, 227) | |
| TOFA | Inhibit ACCA to decrease fatty acid synthesis and induce caspase activation | Inhibit Treg cells proliferation | In vitro: reduce the MCA38 cell viability in a dose-dependent fashion | Tumor-bearing mice | Tumor | (171, 228) | |
| Etomo- xir |
Bind irreversibly to the catalytic site of CPT-1 to inhibit CPT-1 and up-regulate fatty acid oxidase activity | Abrogate Treg cells development and suppressive function | Reduce the production of pro-inflammatory cytokines in MOG specific T cells and promote their apoptosis | C57BL/6J mice | MS | (229, 230) | |
| Amino acid metabolism | DON | Inhibit glutaminase and glutamine transporters | Promote Treg cells generation and frequency | Decrease IFN-γ production and proliferation in activated CD4+ and CD8+ T cells | C57BL/6 mice | Skin and heart transplantation | (231, 232) |
| mTOR/AMPK signal pathway | Rapa-mycin | Block mTOR downstream targets, such as p70S6K phosphorylation and activation | Enhance nTreg cells proliferation and function | Suppress proliferation of CD4+ CD25- effector T-cells | Patients with type 1 diabetes and healthy controls | Type 1 diabetes | (233–235) |
| Metfor-min | Activate AMPK in liver cells leads to decreased ACC activity, induction of fatty acid oxidation, and inhibition of adipogenic enzyme expression | Induce Treg cells differentiation | Inhibit IL-17, p-STAT3, and p-mTOR expression | C57BL/6 mice | IBD | (236, 237) |
2-DG, 2-deoxy-d-glucose; ACC, acetyl-coa carboxylase; CK-MB, creatine kinase-mb; DCA, dichloroacetate; DON, 6-diazo-5-oxo-L-norleucine; EAE, experimental autoimmune encephalomyelitis; ECAR, extracellular acidification rate; GBS, Guillain-Barré syndrome; IBD, inflammatory bowel disease; MS, multiple sclerosis; OCR, oxygen consumption rate; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TOFA, 5-tetradecyl-oxy-2-furoic acid.