S3I-201 shows potent inhibition of STAT3 DNA-binding activity with IC50 of 86 μM, and low activity towards STAT1 and STAT5.

Signal transducers and activators of transcription (STATs) are a family of latent cytoplasmic transcription factors that convey signals from the cell membrane to the nucleus. In various human tumors, STAT3 is constitutively activated by aberrant upstream tyrosine kinase activities.STAT signaling is also suspected to play a role in vascular disease since it can be activated through angiotensin II type 1 receptors or the inflammatory mediator interleukin (IL)-6.S3I-201 is an inhibitor of STAT3 transcription factor activation, dimerization, and gene transcription. It can suppress IL-6-induced phosphorylation of STAT3 in T cells with an IC50 value of 38 μM.Inhibiting STAT3 activation with 10 μM S3I-201 was demonstrated to be protective against angiotensin II-induced oxidative stress, endothelial dysfunction, and hypertension in two different models of vascular disease.At 10 μM, S3I-201 has also been used as a means to regress cardiac hypertrophy by inhibiting collagen biosynthesis and decreasing atrial natriuretic factor and β-myosin heavy chain in an in vitro model.