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Overview
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Background
IC50: 12.2 μM for DU145 cellsSTA-21 is a STAT3 inhibitor.STAT-3, a transcription factor encoded by the STAT-3 gene, exists in a latent form in the cytoplasm. STAT-3 will be phosphorylated on tyrosine residues upon receptor activation by cytokines including IL-6, and forms homo- or heterodimers translocating to the cell nucleus. STAT-3 is also the major transcription factor in Th17 cell differentiation, and STAT-3 can be activated in inflamed synovium, which has been demonstrated in a RA animal model.In vitro: Previous in vitro study showed that, in both mouse and human CD4+ T cells, the treatment with STA-21 could induce the expression of FoxP3 and repressed IL-17 expression. In addition, STA-21 was able to prevent both human monocytes and mouse BMM cells from differentiating into osteoclasts [1]. In vivo: In previous animal study, IL-1Ra-KO mice were treated with i.p. injections of STA-21 at 0.5 mg/kg 3 times per week for 3 weeks. Results showed that STA-21 could suppress inflammatory arthritis in IL-1Ra-KO mice. The Th17 cell proportion decreased and the proportion of Treg cells expressing FoxP3 was increased in the spleens of STA-21-treated mice markedly. Moreover, the adoptive transfer of CD4+CD25+ T cells from STA-21-treated IL-1Ra-KO mice suppressed inflammatory arthritis markedly [1]. Clinical trial: The topical efficacy of STA-21on psoriasis has been conducted at 2010, however, this study has been completed [https://clinicaltrials.gov/ct2/show/NCT01047943].
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