2-hydroxy-4-{2-[(4-methylbenzenesulfonyl)oxy]acetamido}benzoic acid

• ChemBase ID: 72549
• Molecular Formular: C16H15NO7S
• Molecular Mass: 365.3578
• Monoisotopic Mass: 365.05692283
• SMILES: c1(ccc(cc1)S(=O)(=O)OCC(=O)Nc1ccc(c(c1)O)C(=O)O)C
• Canonical SMILES: O=C(Nc1ccc(c(c1)O)C(=O)O)COS(=O)(=O)c1ccc(cc1)C
• 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)
• InChIKey: HWNUSGNZBAISFM-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-hydroxy-4-{2-[(4-methylbenzenesulfonyl)oxy]acetamido}benzoic acid
• IUPAC Traditional name: 2-hydroxy-4-{2-[(4-methylbenzenesulfonyl)oxy]acetamido}benzoic acid
• Synonyms: NSC 74859; S31-201

Database IDs

• CAS Number: 501919-59-1
• PubChem SID: 162037474
• PubChem CID: 252682

CALCULATED PROPERTIES

• Acid pKa: 2.872063
• H Acceptors: 6
• H Donor: 3
• LogD (pH = 5.5): 0.384205
• LogD (pH = 7.4): -0.5261129
• Log P: 2.9618375
• Molar Refractivity: 89.803 cm^3
• Polarizability: 34.471756 Å^3
• Polar Surface Area: 130.0 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: STAT

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1155

Research Area

• Description: Cancer

Biological Activity

• Description: S3I-201 (NSC 74859) is a Stat3 inhibitor with IC50 of 86 μM.
• Targets: Stat3
• IC50: 86 μM ^[1]
• 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: S3I-201 is a chemical probe inhibitor of Stat3 activity.

Protocol

• Protocol: 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 reader.
• Protocol: Cell Assay ^[2]
• Cell Lines: MDA-MB-435, MDA-MB-453 and MDA-MB-231 cells lines
• Concentrations: ~ 250 μM
• Incubation Time: 72 hours
• Methods: 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.
• Protocol: 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.
• Formulation: S3I-201 is formulated in DMSO.
• Doses: ≤5 mg/kg
• Administration: Administered via i.v.

References

• References: [1] Siddiquee K, et al. Proc Natl Acad Sci U S A, 2007, 104(18), 7391-7396.
• References: [2] Lin L, et al. Oncogene, 2009, 28(7), 961-972.
• References: [3] Chen W, et al. Liver Int, 2012, 32(1), 70-77.
• References: [4] Sen N, et al. Proc Natl Acad Sci U S A, 2012, 109(2), 600-605.

REFERENCES

• Siddiquee K, et al. Proc Natl Acad Sci U S A, 2007, 104(18), 7391-7396.
• Lin L, et al. Oncogene, 2009, 28(7), 961-972.
• Sen N, et al. Proc Natl Acad Sci U S A, 2012, 109(2), 600-605.
• Chen W, et al. Liver Int, 2012, 32(1), 70-77.