Table 3.
Preclinical data of drugs that target metabolic pathway.
| Pathway | Animal Model | Effect on Cells | Reference |
|---|---|---|---|
| glycolysis (HK II) | K/BxN | Genetic ablation of HK2 inhibits invasive capacities of FLS and secretion of inflammatory ctytokines. | [75,78], |
| glycolytic inhibitors (2DG, bromopyruvate and ionidamine) |
K/BxN, CIA, SKG | Glycolytic inhibitors reduced FLS aggressive phenotype, decrease effector CD4+ cells, and modulated Th17/Treg differentiation. | [60,76,77,78] |
| glycolysis (PFKFB) | CIA | PFKFB3 inhibition reduced FLS migration and invasion, and the production of inflammatory mediators | [86] |
| glycolysis (FPB) | AIA, zymosan | Systemic generation of extracellular adenosine and subsequent activation of adenosine receptor A2a | [87] |
| succinate receptor (SUCNR1) | AIA | Sucnr1 guides dendritic cells into the lymph nodes, leading the expansion of the Th17-cell population | [100] |
| glutaminase 1 (GLS1) | K/BxN | Inhibition or genetic ablation of glutaminase 1 (GLS1) inhibits RA-FLS proliferation | [43] |
| choline kinase | K/BxN | Blocking choline kinase activity limits the proliferative and migratory capacity of FLS | [109] |
| amino acid uptake (BCAT1) metformin |
CIA CIA, CAIA, K/BxN |
BCAT Inhibition reduces IRG1 and itaconate levels in macrophages. | [138] |
| Metformin modulated Th17/Treg differentiation and osteoclastogenesis. | [122,123,124] |
CIA: collagen-induced arthritis, AIA: antigen-induced arthritis, CAIA: collagen antibody-induced arthritis.