Stattic

Catalog No.S7024

Stattic, the first nonpeptidic small molecule, potently inhibits STAT3 activation and nuclear translocation with IC50 of 5.1 μM in cell-free assays, highly selectivity over STAT1.

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Stattic Chemical Structure

Stattic Chemical Structure
Molecular Weight: 211.19

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Product Information

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Product Description

Biological Activity

Description Stattic, the first nonpeptidic small molecule, potently inhibits STAT3 activation and nuclear translocation with IC50 of 5.1 μM in cell-free assays, highly selectivity over STAT1.
Targets STAT3 [1]
(Cell-free assay)
IC50 5.1 μM
In vitro Stattic inhibits binding of a phosphotyrosine-containing peptide derived from the gp130 receptor to the STAT3 SH2 domain in a strongly temperature-dependent manner. Stattic only has a very weak effect on binding of a tyrosinephosphorylated peptide to the SH2-domain of the tyrosine kinase Lck. And it doesn’t inhibit dimerization of two other dimeric transcription factors (c-Myc/Max and Jun/Jun). It also inhibits fluorescein-labeled phosphopeptides to the SH2 domains of STAT1 and STAT5b. Stattic selectively inhibits DNA binding of STAT3 homodimers at a concentration of 10 μM. Shown to inhibit cellular phosphorylation of STAT3 at Tyr705 with little effect towards STAT1 phosphorylation at Tyr701 (in HepG2 cells) or the phosphorylation of JAK1, JAK2, and c-Src (in MDA-MB-231 and MDA-MB-235S cells). Stattic increases the apoptotic rate of STAT3-dependent breast cancer cell lines. [1]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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MDA-MB-435SNES0NoFCeG:ydH;zbZMhSXO|YYm=M2LVWlExKM7:TR?=NHjXWGkzPCCqNGf2fJVFVVORwrC=NV[5RZVucW6mdXPld{BieG:ydH;zbZM>M{PVVlE4OTF2MEC1

... Click to View More Cell Line Experimental Data

In vivo
Features Stattic is the first non-peptide small molecule with inhibitory activity against STAT3 SH2 domain regardless of the STAT3 phosphorylation state in vitro.

Protocol(Only for Reference)

Kinase Assay: [1]

High-Throughput Screening and Fluorescence Polarization Assays Screening is performed at approximately 30 °C. The specificity of screening hits is validated in analogous assays for binding of the test compounds to the SH2 domains of STAT1, STAT5, and Lck. The final concentration of buffer components used for all FP assays is 10 mM HEPES (pH 7.5), 1 mM EDTA, 0.1% Nonidet P-40, 50 mM NaCl, and 10% DMSO. The absence of dithiothreitol is essential for inhibitory activity. The sequences of the peptides are: STAT3, 5-carboxyfluorescein-GY(PO3H2)LPQTV-NH2; STAT1, 5-carboxyfluorescein-GY(PO3H2)DKPHVL; STAT5, 5-carboxyfluorescein-GY(PO3H2)LVLDKW; and Lck, 5-carboxyfluorescein-GY(PO3H2)EEIP. For specificity analysis at 30 °C, proteins are used at 150 nM (STAT1, STAT3, and STAT5). For specificity analysis at 37 °C, proteins are used at 370 nM (STAT3) or 100 nM (Lck). Proteins are incubated with test compounds in Eppendorf tubes at the indicated temperatures for 60 min prior addition of the respective 5-carboxyfluorescein labeled peptides (final concentration: 10 nM). Before measurement at room temperature, the mixtures are allowed to equilibrate for at least 30 min. Test compounds are used at the indicated concentrations diluted from a 20× stock in DMSO. Binding curves and inhibition curves are fitted with SigmaPlot. All competition curves are repeated three times in independent experiment

Cell Assay: [2]

Cell lines Ly3 cells
Concentrations ~2.5 μM
Incubation Time 48 h
Method MTS

Animal Study: [2]

Animal Models Ly3 parental NOD/SCID IL2R null xenograft
Formulation
Dosages 3.75 mg/kg every day
Administration i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Schust J, et al. Chem Biol, 2006, 13(11), 1235-1242.

[2] Scuto A, et al. Cancer Res, 2011, 71(9), 3182-3188.

Chemical Information

Download Stattic SDF
Molecular Weight (MW) 211.19
Formula

C8H5NO4S

CAS No. 19983-44-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 42 mg/mL (198.87 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 2% DMSO+corn oil 5mg/mL
* <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.
Chemical Name Benzo[b]thiophene, 6-nitro-, 1,1-dioxide

Customer Product Validation(2)


Click to enlarge
Rating
Source J Biol Chem 2013 288(8), 5553-61. Stattic purchased from Selleck
Method Cell migration and Cell Invasion Assays
Cell Lines LN229 cells
Concentrations 10 uM
Incubation Time 24 h
Results Pharmacologic inhibition of the STAT3 SH2 domain with a small molecule inhibitor, Stattic, reversed the increased migration and invasion of CypD-silenced LN229 cells compared with control cultures.

Click to enlarge
Rating
Source FEBS Lett 2014 10.1016/j.febslet.2014.11.023. Stattic purchased from Selleck
Method Western blot
Cell Lines THP-1 cells
Concentrations 10 uM
Incubation Time 1 h
Results To address whether the upregulation of ABCA/G1 expression by DKK1 was mediated through an STAT3 pathway, it used Stattic, a selective STAT3 inhibitor, to inhibit STAT3 phosphorylation (C, P<0.05), and found a significantly impaired effect of rDKK1 on ABCA/G1 expression (D, P<0.05).

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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