| 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(xì)胞實(shí)驗(yàn) | 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(shí)驗(yàn) | 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(xì)胞 PANC-1 和 BxPc-3 用 Stattic (1-10 μM) 處理 12-48 h，使用 CCK-8 方法檢測(cè)細(xì)胞活力。
結(jié)果：Stattic 以濃度和時(shí)間依賴的方式降低 PANC-1 和 BxPc-3 細(xì)胞增殖。Stattic 處理 24 h 后對(duì) BxPc-3 和 PANC-1 細(xì)胞的 IC50 分別為 3.135-5.296?μM 和 3.835-4.165?μM。[1]
方法：人肝癌細(xì)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(cè)靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：Stattic 的預(yù)孵育導(dǎo)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(nèi)活性 | 方法：為檢測(cè)體內(nèi)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(jié)果：Stattic 通過滅活 STAT3 來抑制裸鼠腫瘤模型中的 PC 生長(zhǎng)。[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(dǎo)急性肝損傷的 BALB/c 小鼠。
結(jié)果：Stattic 對(duì) LPS/d-GalN 誘導(dǎo)的肝損傷具有保護(hù)作用，其保護(hù)作用可能與其抗炎和抗凋亡作用有關(guān)。[3] |
| 存儲(chǔ)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), Working solution is recommended to be prepared and used immediately.
DMSO : 55 mg/mL (260.43 mM)
|
| 關(guān)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(guān)產(chǎn)品 | Lidocaine hydrochloride | Metronidazole | 5-Fluorouracil | Stavudine | Tributyrin | Dextran sulfate sodium salt (MW 4500-5500) | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Sodium 4-phenylbutyrate | Kaempferol |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 細(xì)胞凋亡化合物庫(kù) | 高選擇性抑制劑庫(kù) | 抗衰老化合物庫(kù) | 干細(xì)胞分化化合物庫(kù) | 癌細(xì)胞分化化合物庫(kù) | 抗肺癌化合物庫(kù) | 表型篩選靶點(diǎn)鑒定庫(kù) |