NSC 74859 (S3I-201)

Catalog No.S1155 Batch:S115501

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Technical Data

Formula

C16H15NO7S
Molecular Weight 365.36 CAS No. 501919-59-1
Solubility (25°C)* In vitro DMSO 73 mg/mL (199.8 mM)
Ethanol 3 mg/mL (8.21 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description NSC 74859 (S3I-201) shows potent inhibition of STAT3 DNA-binding activity with IC50 of 86 μM in cell-free assays, and low activity towards STAT1 and STAT5.
Targets
STAT3 [1]
(Cell-free assay)
86 μM
In vitro S3I-201 inhibits growth and induces apoptosis preferentially in tumor cells that contain persistently activated Stat3 by inhibiting Stat3·Stat3 complex formation and Stat3 DNA-binding and transcriptional activitie. Moreover, S3I-201 also inhibits the expression of the Stat3-regulated genes encoding cyclin D1, Bcl-xL, and survivin. [1] S3I-201 inhibits breast carcinoma MDA-MB-435, MDA-MB-453 and MDA-MB-231 cell lines with IC50 of 100 μM. In addition, the cells with impaired TGF-β signaling are four times as sensitive to the STAT3 inhibitor S3I-201. [2] A recent study shows that S3I-201 potentiates the antiproliferative effect of cetuximab in HepG2 and Huh-7 cells via the STAT3 signalling pathway. [3]
In vivo S3I-201 (5 mg/kg, i.v. every 2 or every 3 days) shows the antitumor efficacy in mouse models with human breast tumor xenografts that harbor constitutively active Stat3. [1] S3I-201 treatment reduces Varicella-zoster virus (VZV) replication on the basis of the bioluminescence signal and the number of positive skin xenografts compared with DMSO-treated mice by inhibiting STAT3 phosphorylation. [4]
Features A chemical probe inhibitor of Stat3 activity.

Protocol (from reference)

Kinase Assay:[1]
  • In vitro Stat3 DNA-binding assay and EMSA analysis

    Briefly, 100 mL of biotinyl-e-Ac-EPQpYEEIEL-OH (in 50 mM Tris/150 mM NaCl, pH 7.5) is added to each well of streptavidin-coated 96-well microtiter plates and incubated with shaking at 4 °C overnight. Then plates are rinsed with PBS/Tween 20 and then two times with 200 mL of BSA-T-PBS (0.2% BSA/0.1% Tween 20/PBS). Then 50 mL of Lck-SH2-GST fusion protein (6.4 ng/ml in BSA-T-PBS) is added to each well of the 96-well plate in the presence and absence of 50 mL of S3I-201 (for 30 and 100 mM final concentrations), and the plate is shaken at room temperature for 4 hours. After solutions are removed, each well is rinsed four times with BSA-T-PBS (200 mL), and 100 mL of polyclonal rabbit anti-GST antibody (100 ng/mL in BSA-T-PBS) is added to each well and incubated at 4 °C overnight. After washing with BSA-T-PBS, 100 mL of 200 ng/mL BSA-T-PBS horseradish peroxidase-conjugated mouse anti-rabbit antibody is added to each well and incubated for 45 minutes at room temperature. After four washing steps with BSA-T-PBS and three washing steps with PBS-T, 100 mL of peroxidase substrate is added to each well and incubated for 5-15 minutes. The peroxidase reaction is stopped by adding 100 mL of 1 M sulfuric acid solution, and absorbance is read at 450 nm with an ELISA plate rea
Cell Assay:[2]
  • Cell lines

    MDA-MB-435, MDA-MB-453 and MDA-MB-231 cells lines

  • Concentrations

    ~ 250 μM

  • Incubation Time

    72 hours

  • Method

    The MTT assay is based on the conversion of the yellow tetrazolium salt MTT to purple formazan crystals by metabolically active cells. The MTT assay provides a quantitative determination of viable cells. Cells are seeded in 96-well microplates in complete culture medium in the absence or presence of increasing serial dosages of S3I-201 as indicated. At 72 hours after culture, the number of viable cells is measured by adding 100 μL/well of 2 mg/mL MTT solution. After 2 hours, the medium is removed, and the formazan crystals are dissolved by adding 100 μL dimethylsulfoxide per well. The absorbance is read at 590 nm with an enzyme-linked immunosorbent assay reader. Each treatment point is performed in 10 wells or sextuplicate.
Animal Study:[1]
  • Animal Models

    Human breast cancer MDA-MB-231 cells are injected s.c. into the left flank of athymic nu/nu mice.

  • Dosages

    ≤5 mg/kg

  • Administration

    Administered via i.v.

Customer Product Validation

Data from [Data independently produced by Mol Cancer, 2014, 13:176]

Data from [Data independently produced by Int Immunopharmacol, 2014, 20(1), 117-23]

Data from [Data independently produced by Microbes Infect, 2014, 16(1), 17-27]

Data from [Data independently produced by Clin Cancer Res, 2013, 19(6), 1422-32]

Selleck's NSC 74859 (S3I-201) has been cited by 232 publications

Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation [ Am J Respir Cell Mol Biol, 2024, 70(1):26-38] PubMed: 37699145
SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation [ Mol Ther, 2023, 31(3):774-787] PubMed: 36523164
Nuclear translocation of thioredoxin-1 promotes colorectal cancer development via modulation of the IL-6/STAT3 signaling axis through interaction with STAT3 [ Theranostics, 2023, 13(14):4730-4744] PubMed: 37771783
Nuclear translocation of thioredoxin-1 promotes colorectal cancer development via modulation of the IL-6/STAT3 signaling axis through interaction with STAT3 [ Theranostics, 2023, 13(14):4730-4744] PubMed: 37771783
A large-scale transcriptional analysis reveals herb-derived ginsenoside F2 suppressing hepatocellular carcinoma via inhibiting STAT3 [ Phytomedicine, 2023, 120:155031] PubMed: 37666060
Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling [ Breast Cancer Res, 2023, 25(1):43] PubMed: 37069669
Adjuvant activity of tubeimosides by mediating the local immune microenvironment [ Front Immunol, 2023, 14:1108244] PubMed: 36845089
IL-21 is required for the maintenance and pathogenesis of murine Vγ4+ IL-17-producing γδT cells [ Front Immunol, 2023, 14:1211620] PubMed: 37662923
IGFBP2 promotes proliferation and cell migration through STAT3 signaling in Sonic hedgehog medulloblastoma [ Acta Neuropathol Commun, 2023, 11(1):62] PubMed: 37029430
Analyzing the role of cancer-associated fibroblast activation on macrophage polarization [ Mol Oncol, 2023, 17(8):1492-1513] PubMed: 37199012

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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