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Overview
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Background
S3I-201 is a selective inhibitor of Stat3 with IC50 value of 86 μM [1].
In the in vitro Stat3 DNA-binding assay, S3I-201 showed potent inhibition of the Stat3 DNA-binding activity with an average IC50 of 86 μM. In the EMSA assay, S3I-201 selectively inhibited Stat3 DNA-binding activity over that of Stat1 and Stat5. It suppressed the complex formation of Stat1-Stat3 and Stat1-Stat1 with IC50 values of 160 and > 300 μM, respectively. Besides that, the unphosphorylated, inactive Stat3 monomer was found to restore the Stat3 DNA-binding activity inhibited by S3I-201, suggesting that the inhibition was independent on the activation status. In NIH 3T3/v-Src fibroblasts, S3I-201 inhibited the constitutive activation of Stat3 and reduced the pTyr-705 Stat3 levels. Moreover, S3I-201 was found to significantly induce apoptosis in cells with constitutively active Stat3 at concentration of 30–100 μM. S3I-201 also reduced the expression of cyclin D1, Bcl-xL and surviving in these cells [1].[1] Siddiquee K, Zhang S, Guida W C, et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proceedings of the National Academy of Sciences, 2007, 104(18): 7391-7396.
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