NSC 74859Stat3 inhibitor CAS# 501919-59-1 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 501919-59-1 | SDF | Download SDF |
PubChem ID | 252682 | Appearance | Powder |
Formula | C16H15NO7S | M.Wt | 365.36 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | S3I-201 | ||
Solubility | DMSO : 100 mg/mL (273.70 mM; Need ultrasonic) | ||
Chemical Name | 2-hydroxy-4-[[2-(4-methylphenyl)sulfonyloxyacetyl]amino]benzoic acid | ||
SMILES | CC1=CC=C(C=C1)S(=O)(=O)OCC(=O)NC2=CC(=C(C=C2)C(=O)O)O | ||
Standard InChIKey | HWNUSGNZBAISFM-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C16H15NO7S/c1-10-2-5-12(6-3-10)25(22,23)24-9-15(19)17-11-4-7-13(16(20)21)14(18)8-11/h2-8,18H,9H2,1H3,(H,17,19)(H,20,21) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Selectively inhibits STAT3 DNA-binding activity in vitro (IC50 values are 86, 160, and >300 μM for STAT3-STAT3, STAT1-STAT3 and STAT1-STAT1 DNA-binding activity respectively). Blocks growth and induces apoptosis preferentially in tumor cells that contain persistently active STAT3 in vitro and arrests tumor growth in a murine xenograft model in vivo. |
NSC 74859 Dilution Calculator
NSC 74859 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.737 mL | 13.6851 mL | 27.3703 mL | 54.7405 mL | 68.4257 mL |
5 mM | 0.5474 mL | 2.737 mL | 5.4741 mL | 10.9481 mL | 13.6851 mL |
10 mM | 0.2737 mL | 1.3685 mL | 2.737 mL | 5.4741 mL | 6.8426 mL |
50 mM | 0.0547 mL | 0.2737 mL | 0.5474 mL | 1.0948 mL | 1.3685 mL |
100 mM | 0.0274 mL | 0.1369 mL | 0.2737 mL | 0.5474 mL | 0.6843 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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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].
References:
[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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The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling.[Pubmed:19137011]
Oncogene. 2009 Feb 19;28(7):961-72.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, with few effective therapeutic options for advanced disease. At least 40% of HCCs are clonal, potentially arising from STAT3+, NANOG+ and OCT3/4+ liver progenitor/stem cell transformation, along with inactivation of transforming growth factor-beta (TGF-beta) signaling. Here we report significantly greater signal transducer and activator of transcription 3 (STAT3) and tyrosine phosphorylated STAT3 in human HCC tissues (P<0.0030 and P<0.0455, respectively) than in human normal liver. Further, in HCC cells with loss of response to TGF-beta, NSC 74859, a STAT3-specific inhibitor, markedly suppresses growth. In contrast, CD133(+) status did not affect the response to STAT3 inhibition: both CD133(+) Huh-7 cells and CD133(-) Huh-7 cells are equally sensitive to NSC 74859 treatment and STAT3 inhibition, with an IC(50) of 100 muM. Thus, the TGF-beta/beta2 spectrin (beta2SP) pathway may reflect a more functional 'stem/progenitor' state than CD133. Furthermore, NSC 74859 treatment of Huh-7 xenografts in nude mice significantly retarded tumor growth, with an effective dose of only 5 mg/kg. Moreover, NSC 74859 inhibited tyrosine phosphorylation of STAT3 in HCC cells in vivo. We conclude that inhibiting interleukin 6 (IL6)/STAT3 in HCCs with inactivation of the TGF-beta/beta2SP pathway is an effective approach in management of HCCs. Thus, IL6/STAT3, a major signaling pathway in HCC stem cell renewal and proliferation, can provide a novel approach to the treatment of specific HCCs.
NSC 74859-mediated inhibition of STAT3 enhances the anti-proliferative activity of cetuximab in hepatocellular carcinoma.[Pubmed:22098470]
Liver Int. 2012 Jan;32(1):70-7.
BACKGROUND: Cetuximab [an epidermal growth factor receptor (EGFR) inhibitor], which was shown to be effective in rectal and non-small cell lung cancers (NSCLCs), was only modestly effective in clinical trials of hepatocellular carcinoma (HCC). STAT3, which is thought to be a determinant of HCC sensitivity to antitumour drugs, may be involved. AIMS: To evaluate the efficacy of combination therapy using cetuximab and NSC 74859 (a novel STAT3 inhibitor) in EGFR and STAT3 overexpressing hepatoma cells. METHODS: Hepatoma cell lines were treated with cetuximab, NSC 74859 or a combination of both drugs. Efficacy of treatment was evaluated by determining cell viability using MTT assays and proliferation by cell counting. Expression and activation of STAT3 were determined using Western blot analysis. We evaluated the role of STAT3 in single and combination therapy using siRNA-mediated knock-down of STAT3 or STAT3 overexpression strategies. RESULTS: HepG2 and Huh-7 cells, which had lower levels of pSTAT3 than SK-HEP1 cells, were more sensitive to cetuximab treatment when compared with SK-HEP1 cells. Although none of these cell lines was sensitive to NSC 74859 alone, NSC 74859 potentiated the antiproliferative effect of cetuximab in all three cell lines. siRNA knock-down of STAT3 increased the sensitivity of these cell lines to cetuximab, whereas STAT3 overexpression antagonized these effects. CONCLUSIONS: Enhanced growth inhibition in hepatoma cells treated with both NSC 74859 and cetuximab suggests that cetuximab resistance is probably mediated via STAT3. Combination therapy using both inhibitors of EGFR and STAT3 signalling warrants further investigation under in vivo condition.
NSC 74859 enhances doxorubicin cytotoxicity via inhibition of epithelial-mesenchymal transition in hepatocellular carcinoma cells.[Pubmed:22781398]
Cancer Lett. 2012 Dec 28;325(2):207-13.
Doxorubicin-based therapy is not effective for the treatment of hepatocellular carcinomas (HCCs), which often undergo epithelial-mesenchymal transition (EMT) during tumor progression. Activation of signal transducer and activator of transcription 3 (STAT3) is associated with chemosensitivity and may contribute to EMT during HCC chemotherapy. Low doses of NSC 78459 (a novel STAT3 inhibitor) have little effect on HCC cell proliferation, but efficiently inhibit STAT3. HuH-7, Hep3B, and HepG2 cells, with epithelial phenotypes, show significantly enhanced doxorubicin cytotoxicity following co-treatment with NSC 74859, whereas mesenchymal SNU-449 cells show no such enhancement. NSC 74859 inhibits STAT3 activity and suppressed doxorubicin-induced EMT in epithelial HCC cells. siRNA-mediated STAT3 knockdown resulted in EMT inhibition, which led to attenuation of NSC 74859-mediated chemosensitivity. Our data indicate NSC 74859 co-administration enhances doxorubicin cytotoxicity by inhibiting STAT3 in epithelial HCC cells. STAT3 deactivation and associated EMT attenuation contribute to the synergistic anti-tumor effects of combined NSC 74859/doxorubicin therapy.
Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity.[Pubmed:17463090]
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7391-6.
S3I-201 (NSC 74859) is a chemical probe inhibitor of Stat3 activity, which was identified from the National Cancer Institute chemical libraries by using structure-based virtual screening with a computer model of the Stat3 SH2 domain bound to its Stat3 phosphotyrosine peptide derived from the x-ray crystal structure of the Stat3beta homodimer. S3I-201 inhibits Stat3.Stat3 complex formation and Stat3 DNA-binding and transcriptional activities. Furthermore, S3I-201 inhibits growth and induces apoptosis preferentially in tumor cells that contain persistently activated Stat3. Constitutively dimerized and active Stat3C and Stat3 SH2 domain rescue tumor cells from S3I-201-induced apoptosis. Finally, S3I-201 inhibits the expression of the Stat3-regulated genes encoding cyclin D1, Bcl-xL, and survivin and inhibits the growth of human breast tumors in vivo. These findings strongly suggest that the antitumor activity of S3I-201 is mediated in part through inhibition of aberrant Stat3 activation and provide the proof-of-concept for the potential clinical use of Stat3 inhibitors such as S3I-201 in tumors harboring aberrant Stat3.