Uses
STA 21 selectively inhibits signal transducers and activators of transcription 3 (Stat3), which is transcription factor that is often found to be constitutively active in human breast cancer (1). It also inhibits osteoclastogenesis in mice and humans (2). In addition, STA 21 has been shown to attenuates the development and progression of inflammation in collagen antibody-induced arthritis and therefore, this compound may be used to develop therapeutic strategies to treat rheumatoid arthritis (3).
Biological Activity
sta-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].
IC 50
12.2 μm for du145 cells
References
[1] park js et al. sta-21, a promising stat-3 inhibitor that reciprocally regulates th17 and treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis. arthritis rheumatol.2014 apr;66(4):918-29.
