A STAT3 inhibitor
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].
参考文献:
[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.
| Cell experiment: [1] | |
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Cell lines |
NIH 3T3/v-Src cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
100 μM, 24 hours |
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Applications |
Viral Src transformed (NIH 3T3/v-Src) mouse fibroblasts stably expressing Stat3-YFP were transiently transfected with Flag-Stat3, treated with NSC-74859, and then subjected to pull-down assay and SDS/PAGE. Western blot analysis for FLAG of whole-cell lysates shows equal expression of the FLAG-ST3 protein in the lysates in the transiently transfected cells in both the control and NSC-74859-treated cells. Western blot analysis probing with anti-FLAG antibody showed no detectable level of FLAG-ST3 protein in the Stat3-YFP immunoprecipitates from NSC-74859-treated cells, suggesting the disruption by NSC-74859 of the complex formation between Stat3-YFP and FLAG-ST3 proteins. |
| Animal experiment: [1] | |
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Animal models |
Female athymic nude mice injected with MDA-MB-231 cells |
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Dosage form |
Intravenous injection, 5 mg/kg every 2 or 3 days for 2 weeks |
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Applications |
Compared with control (vehicle-treated) tumors, which continued to grow, human breast tumors in mice that received NSC-74859 displayed strong growth inhibition. Continued evaluation of treated mice on termination of treatment showed no resumption of tumor growth, suggesting potentially a long-lasting effect of NSC-74859 on tumor growth. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [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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