STA-21, a promising STAT3 inhibitor that reciprocally regulates Th17 and Treg, inhibits osteoclastgenesis and alleviates autoimmune inflammation
STAT3 (signal transducer and activator of transcription 3) is the major transcription factor in the differentiation of Th17 cells, which along with IL-17 are significant in the development of RA. STA-21 is a new small molecule with significant inhibitory effects on STAT3, impeding DNA binding activity, dimerization and STAT3-dependent luciferase activity. While the effect of STA-21 in RA has not been fully determined, it has been hypothesised that STA-21 will suppress arthritis in animal models of RA. Park et al. used several measures, including in vivo testing in IL-1 receptor antagonist deficient mice, to show the therapeutic effect. The effects included the decreased activity of Th17 cells and increased Foxp3-expressing Treg cells. The effects on osteoclasts were also measured and an adoptive transfer of CD4+CD25+ T cells was performed to verify the Treg cells produced by STA-21 would work in vivo. The results obtained suggest that STA-21 presents a potential therapeutic option for RA.