YE6144 is a prototypical interferon regulatory factor 5 (IRF5) inhibitor. YE6144 selectively suppresses IRF5 activity through inhibition of IRF5 phosphorylation[1].
YE6144 (1 or 3 μM; 30 min) inhibits the phosphorylation of IRF5 in both human PBMCs and mouse splenocytes[1].
YE6144 (0-10 μM; 30 min) inhibits the production of type I IFNs with an IC50 of approximately 0.09 μM in human HC PBMCs[1].
Western Blot Analysis[1]
| Cell Line: | Human HC PBMCs and mouse WT splenocytes |
| Concentration: | 1 μM (PBMCs) and 3 μM (splenocytes) |
| Incubation Time: | 30 min |
| Result: | Inhibited the phosphorylation of IRF5. |
RT-PCR[1]
| Cell Line: | Mouse WT splenocytes |
| Concentration: | 3 μM |
| Incubation Time: | 30 min |
| Result: | Induction of type I IFN genes, Ifnb1 and Ifna stimulated by TLR7 ligands or TLR9 ligands was remarkably weakened. |
YE6144 (40.0 mg/kg; s.c.; once) suppresses the progression of mouse systemic lupus erythematosus[1].
| Animal Model: | NZB/W F1 mouse model of systemic lupus erythematosus (SLE)[1] |
| Dosage: | 40.0 mg/kg |
| Administration: | Subcutaneous injection, once |
| Result: | Suppressed the exacerbation of autoantibody production. Splenomegaly and renal dysfunction were also suppressed by the treatment after disease onset. |
[1]. Ban T, et al. Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease. Nat Commun. 2021 Jul 19;12(1):4379.