Stattic
Stattic is a small molecule inhibitor of STAT3 with IC50 values of 2.562 ± 0.409 μM, 3.481 ± 0.953 μM, 2.282 ± 0.423 μM and 2.648 ± 0.542 μM, respectively, in UM-SCC-17B, OSC-19, Cal33 and UM-SCC-22B cell lines [1].
Stattic is reported to selectively inhibit dimerization, activation and nuclear translocation of STAT3. It can also induce the apoptosis of STAT3-dependent breast cancer cell lines [2].
The inhibition of STAT3 by Stattic results in decreased STAT3-mediated HIF-1 expression and subsequent radiosensitization of HNSCC cells. Inhibiting the STAT3 signaling pathway may represent an effective strategy in the treatment of HNSCC. The evidence of Stattic activity in vivo has also been found. Stattic pre-treatment sensitizes orthotopic xenograft HNSCC tumors to radiation, wich results in signi?cantly reduced tumor growth, although this effect was not as dramatic as anticipated by the in vitro studies [1].
References:
[1] Makoto Adachi, Caixia Cui, Cristina T. Dodge, Mihir K. Bhayani, Stephen Y. Lai. Targeting STAT3 inhibits growth and enhances radiosensitivity in head and neck squamous cell carcinoma. Oral Oncology. 2012 July(48):1220-1226.
[2] Jochen Schust, Bianca Sperl, Angela Hollis, Thomas U. Mayer, and Thorsten Berg. Stattic: A Small-Molecule Inhibitor of STAT3 Activation and Dimerization. Chemistry & Biology. 2006(13):1235-1242.
- 1. Junli Wang, Sijia Weng, et al. "PKCι induces differential phosphorylation of STAT3 to modify STAT3-related signaling pathways in pancreatic cancer cells." J Cell Commun Signal. 2023 Aug 7. PMID: 37548811
- 2. Jiang Li, Hong Huang, et al. "Complement factor H inhibits endothelial cell migration through suppression of STAT3 signaling." Exp Ther Med. 2023 Jul 10;26(2):408. PMID: 37522066
- 3. Weibo Zhong, Kaihui Wu, et al. "Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis." Microbiome. 2022 Jun 16;10(1):94. PMID: 35710492
- 4. Ying Zhang, Cong Liu, et al. "IL-22 promotes tumor growth of breast cancer cells in mice." Aging (Albany NY). 2020 Jul 15; 12(13): 13354–13364. PMID: 32649314
- 5. Li L, Shang L, et al. "Janus kinase inhibitor ruxolitinib blocks thymic regeneration after acute thymus injury." Biochem Pharmacol. 2019 Nov 11:113712. PMID: 31726048
- 6. Zhang Q, Liu RX, et al. "Exosomal transfer of p-STAT3 promotes acquired 5-FU resistance in colorectal cancer cells." J Exp Clin Cancer Res. 2019 Jul 19;38(1):320. PMID: 31324203
- 7. Linnan Yang, Jing Sun, et al. "Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment." Advanced Science. 16 February 2019.
- 8. Lee YC, Wang LJ, et al. "ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells." Cancer Lett. 2018 Jun 15;432:191-204. PMID: 29913235
- 9. Kim W, Khan SK, et al. "Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis." J Clin Invest. 2017 Jan 3;127(1):137-152. PMID: 27869648
- 10. Furtek SL, Matheson CJ, et al. "Evaluation of quantitative assays for the identification of direct signal transducer and activator of transcription 3 (STAT3) inhibitors." Oncotarget. 2016 Nov 22;7(47):77998-78008. PMID: 27793003
- 11. Syn Kok Yeo, Jian Wen, et al. "Autophagy differentially regulates distinct breast cancer stem-like cells in murine models via EGFR/Stat3 and Tgf?/Smad signaling." Published OnlineFirst April 13, 2016.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 211.19 |
Cas No. | 19983-44-9 |
Formula | C8H5NO4S |
Solubility | insoluble in H2O; insoluble in EtOH; ≥10.56 mg/mL in DMSO |
Chemical Name | 6-nitro-1-benzothiophene 1,1-dioxide |
SDF | Download SDF |
Canonical SMILES | C1=CC(=CC2=C1C=CS2(=O)=O)[N+](=O)[O-] |
Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Kinase experiment [1]: | |
High-throughput screening and fluorescence polarization assays |
Screening was performed at approximately 30°C. The specificity of screening hits was 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 were: 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 were used at 150 nM (STAT1, STAT3, and STAT5). For specificity analysis at 37 °C, proteins were used at 370 nM (STAT3) or 100 nM (Lck). Proteins were 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 were allowed to equilibrate for at least 30 mins. Test compounds were used at the indicated concentrations diluted from a 20× stock in DMSO. Binding curves and inhibition curves were fitted with SigmaPlot. All competition curves were repeated three times in independent experiment. |
Cell experiment [2]: | |
Cell lines |
Head and neck squamous cell carcinoma (HNSCC) cell lines UM-SCC-17B, OSC-19, Cal33, and UM-SCC-22B |
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions |
0 ~ 100 M; 24 hrs |
Applications |
Stattic significantly inhibited STAT3 activation and expression, leading to decreased cell survival and proliferation as well as increased radiosensitivity. The Stattic treatment also reduced STAT3-mediated HIF-1 expression. |
Animal experiment [2]: | |
Animal models |
UM-SCC-17B cells xenografted mouse model |
Dosage form |
50 mg/kg; p.o.; 5 days a week for 4 weeks |
Applications |
In a murine orthotopic xenograft, oral administration of Stattic effectively reduced the growth of HNSCC tumors, and analysis of tumor lysates validated decreased STAT3 phosphorylation. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Jochen Schust, Bianca Sperl, Angela Hollis, Thomas U. Mayer, and Thorsten Berg. Stattic: A Small-Molecule Inhibitor of STAT3 Activation and Dimerization. Chemistry & Biology. 2006(13):1235-1242. [2]. Makoto Adachi, Caixia Cui, Cristina T. Dodge, Mihir K. Bhayani, Stephen Y. Lai. Targeting STAT3 inhibits growth and enhances radiosensitivity in head and neck squamous cell carcinoma. Oral Oncology. 2012 July(48):1220-1226. |
Description | Stattic is a small-molecule inhibitor of STAT3 with IC50 values of 2.562 ± 0.409 μM, 3.481 ± 0.953 μM, 2.282 ± 0.423 μM and 2.648 ± 0.542 μM in UM-SCC-17B, OSC-19, Cal33 and UM-SCC-22B cell lines, respectively. | |||||
Targets | STAT3 | STAT3 | STAT3 | STAT3 | ||
IC50 | 2.562 ± 0.409 μM (UM-SCC-17B cell line) | 3.481 ± 0.953 μM (OSC-19 cell line) | 2.282 ± 0.423 μM (Cal33 cell line) | 2.648 ± 0.542 μM (UM-SCC-22B cell line) |
Quality Control & MSDS
- View current batch: