2-Hydroxy-4-[[[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino]-benzoic acid

an inhibitor of STAT3 with anti-tumor activity; NSC 74859 in inhibition of STAT3 dimerization assays demonstrated an IC50 = 100 µM

OTAVAchemicals Catalogue Number: 7070707021

CAS Registry Number: 501919-59-1

Purity: 98% (HPLC)

Ref. : Siddiquee et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proceedings of the National Academy of Sciences of the United States of America (2007), 104, 7391-7396

Abstract: 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 Stat3β 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. A cell-permeable amidosalicylic acid compound that binds Stat3-SH2 domain and prevents Stat3 phosphorylation/activation, dimerization, DNA-binding, and Stat3-dependent transcription. Shown to arrest Stat3-dependent tumor growth both in cultures in vitro (effective conc. =100 µM) and in a murine xenograft model in vivo (5 mg/kg, i.v.). Also available as a 50 mM solution in DMSO.

DOI: 10.1073/pnas.0609757104

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