Description
Stattic (19983-44-9) is a STAT3 inhibitor that inhibits binding of tyrosine-phosphorylated peptides to STAT3 SH2 domain and inhibiting STAT3 activation, dimerization and nuclear translocation.1 Displays selectivity over STAT1, STAT5, c-Myc/Max, Jun/Jun and Lck. Induces apoptosis in STAT3-dependent cancer cell lines. Alkyates four cysteine residues on STAT3.2 Exhibits potent antitumor activity.3 Protects against angiotensin II-induced vascular dysfunction and hypertension.4?Stattic is an extremely useful tool to probe involvement of STAT3 in cellular signaling.
Uses
Stattic is a Stat3 inhibitor which exhibited potent anti-tumor and induced chemo- and radio-sensitivity in nasopharyngeal carcinoma.
Definition
ChEBI: Stattic is a member of the class of 1-benzothiophenes that is 1-benzothiophene-1,1-dioxide substituted at position 6 by a nitro group. Used as a radiosensitising agent for esophageal squamous cell carcinoma. It has a role as an antineoplastic agent, a STAT3 inhibitor and a radiosensitizing agent. It is a member of 1-benzothiophenes, a C-nitro compound and a sulfone.
Biological Activity
Small molecule inhibitor of STAT3. Inhibits binding of tyrosine-phosphorylated peptide motifs to STAT3 SH2 domain and inhibits STAT3 activation, dimerization and nuclear translocation. Displays selectivity over STAT1, STAT5, c-Myc/Max, Jun/Jun and Lck. Induces apoptosis in STAT3-dependent cancer cell lines.
Biochem/physiol Actions
Stattic (Stat3 three inhibitory compound) alters the SH2 domain of Stat3 and indirectly inhibits with phosphopeptide binding. It is readily transported across the cell membrane compared to other phosphopeptides.2 Stattic induces increased formation of ROS and negatively affects the cardiomyocyte mitochondrial function,3 and sensitizes nasopharyngeal carcinoma cells to chemoradiotherapy.4
References
1) Schust et al. (2006), Stattic: a small molecule inhibitor of STAT3 activation and dimerization; Chem. Biol., 13 1235
2) Heidelberger et al. (2013), Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry; Bioorg. Med. Chem. Lett., 23 4719
3) Pan et al. (2013), Stat3 inhibitor Stattic exhibits potent anti-tumor activity and induces chemo- and radio-sensitivity in nasopharyngeal carcinoma; PLoS One, 8(1) e54565
4) Johnson et al. (2013), Small-molecules inhibitors of signal transducer and activator of transcription 3 protect against angiotensin II-induced vascular dysfunction and hypertension; Hypertension, 61 437
