| 名稱 | Stattic |
| 描述 | Stattic (STAT3 Inhibitor V) is a STAT3 inhibitor (IC50=5.1 μM) that selectively inhibits STAT3 activation, dimerization, and nuclear translocation. Stattic has antitumor activity and induces apoptosis. |
| 細胞實驗 | MDA-MB-231, MDA-MB-435S, and MDA-MB-453 cells were seeded. at 5 × 10^4 cells in 6-well plates, grown for 24 hr before adding DMSO or Stattic (final DMSO concentration 0.1%) and then incubated with the inhibitor for 24 hr. All cells were collected and resuspended in buffer (0.1% sodium citrate, 0.1% Triton X-100, 20 μM propidium iodide) and incubated for 3 hr before 10^4 cells per sample were analyzed by flow cytometry with a FACSCalibur equipped with a 488 nm laser [1]. |
| 激酶實驗 | The screening was performed at approximately 30C. 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 was 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. Peptides were >95% pure. 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 tubes at the indicated temperatures for 60 min prior addition of the respective 5-carboxyfluorescein labeled peptides (final concentration: 10 nM). Analysis of c-Myc/Max and Jun/Jun dimerization and DNA binding at 37°C was performed as described but in the absence of DTT. Before measurement at room temperature, the mixtures were allowed to equilibrate for at least 30 min. Test compounds were used at the indicated concentrations diluted from 20× stock in DMSO. Binding curves and inhibition curves were fitted with SigmaPlot. All competition curves were repeated three times in independent experiments. For the analysis of time dependence of the inhibition, the components were mixed from stock solutions kept at 0C and then incubated at 37C. Aliquots were taken at the indicated time points [1]. |
| 體外活性 | 方法：人胰腺癌細胞 PANC-1 和 BxPc-3 用 Stattic (1-10 μM) 處理 12-48 h，使用 CCK-8 方法檢測細胞活力。
結果：Stattic 以濃度和時間依賴的方式降低 PANC-1 和 BxPc-3 細胞增殖。Stattic 處理 24 h 后對 BxPc-3 和 PANC-1 細胞的 IC50 分別為 3.135-5.296?μM 和 3.835-4.165?μM。[1]
方法：人肝癌細胞 HepG2 用 Stattic (5-20 μM) 處理 1 h，隨后用 IL-6 或 IFN-γ刺激，使用 Western Blot 方法檢測靶點蛋白表達水平。
結果：Stattic 的預孵育導致 STAT3 Tyr705 的磷酸化選擇性降低，而 STAT1 Tyr701 的激活保持不變。[2] |
| 體內活性 | 方法：為檢測體內抗腫瘤活性，將 Stattic (10 mg/kg) 腹腔注射給攜帶人胰腺癌腫瘤 PANC-1 的 BALB/c nude 小鼠，每天一次，持續(xù)四周。
結果：Stattic 通過滅活 STAT3 來抑制裸鼠腫瘤模型中的 PC 生長。[1]
方法：為研究在急性肝損傷中的作用，將 Stattic (5 mg/kg in DMSO:olive oil?=?1:19) 單次腹腔注射給? LPS/d-GalN 誘導急性肝損傷的 BALB/c 小鼠。
結果：Stattic 對 LPS/d-GalN 誘導的肝損傷具有保護作用，其保護作用可能與其抗炎和抗凋亡作用有關。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 1.1 mg/mL (5 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1.06 mg/mL (5.02 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
DMSO : 55 mg/mL (260.43 mM)
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| 關鍵字 | inhibit | Alport | PC3M-1E8 | cancer | p-STAT3 | prostate | Stattic | S727 | Apoptosis | syndrome | Inhibitor | P-ERK1/2 | SH2 | STAT | S phase | Y705 |
| 相關產品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
| 相關庫 | 抑制劑庫 | 經典已知活性庫 | 已知活性化合物庫 | 細胞凋亡化合物庫 | 高選擇性抑制劑庫 | 抗衰老化合物庫 | 干細胞分化化合物庫 | 癌細胞分化化合物庫 | 抗肺癌化合物庫 | 表型篩選靶點鑒定庫 |