| 名稱 | TPCA-1 |
| 描述 | TPCA-1 (TPCA1) is an effective and specific IKK-2 inhibitor (IC50: 17.9 nM); shows >22-fold selectivity over IKK-1 and >550-fold selectivity over others kinases and enzymes. |
| 細(xì)胞實(shí)驗(yàn) | Ten microliters of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) from stock solution (10?mg/mL) is added to each well of 96-well plates containing glioma cells and incubated at 37 °C for 2–4?h. Oxidized MTT is solubilized by adding 100?μL of 10% sodium dodecyl sulfate (SDS) in 0.01?N HCL, and plates are incubated at 37 °C for 4?h in a humidified chamber. Plates are read at 570?nm on a plate reader.(Only for Reference) |
| 激酶實(shí)驗(yàn) | IKK-2 Assay: Recombinant human IKK-2 (residues 1-756) is expressed in baculovirus as an N-terminal GST-tagged fusion protein, and its activity is assessed using a time-resolved fluorescence resonance energy transfer assay. In brief, IKK-2 (5 nM final) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM CHAPS, pH 7.4, with 1 mM DTT and 0.01% w/v BSA) is added to wells containing various concentrations of compound or dimethyl sulfoxide (DMSO) vehicle (3% final). The reaction is initiated by the addition of GST-IκBα substrate (25 nM final)/ATP (1 μM final), in a total volume of 30 μL. The reaction is incubated for 30 min at room temperature, then terminated by the addition of 15 μL of 50 mM EDTA. Detection reagent (15 μL) in buffer (100 mM HEPES, pH 7.4, 150 mM NaCl, and 0.1% w/v BSA) containing antiphosphoserine- IκBα-32/36 monoclonal antibody 12C2, labeled with W-1024 europium chelate, and an allophycocyanin-labeled anti-GST antibody is added, and the reaction is further incubated for 60 min at room temperature. The degree of phosphorylation of GST- IκBαis measured as a ratio of specific 665-nm energy transfer signal to reference europium 620-nm signal, using a Packard Discovery plate reader. |
| 體外活性 | TPCA-1可顯著減少體內(nèi)膠原誘導(dǎo)的T細(xì)胞增殖.TPCA-1（3/10/20 mg/kg,i.p.,b.i.d.）預(yù)防性給藥,使小鼠體內(nèi)膠原誘導(dǎo)性關(guān)節(jié)炎的嚴(yán)重程度呈劑量依賴性降低.TPCA-1（20 mg/kg,i.p.,b.i.d.）可明顯降低CIA的嚴(yán)重程度,與依那西普（12.5 mg/kg,i.p.）每隔一天給藥的效果相同.TPCA-1（10 mg/kg,i.p.,b.i.d.）使疾病嚴(yán)重程度明顯降低,并使疾病發(fā)作的延遲,這與依那西普（4 mg/kg,i.p.）每隔一天預(yù)防性給藥的效果相當(dāng). |
| 體內(nèi)活性 | TPCA-1對(duì)TNF-α（IC50：170 nM）,IL-6（IC50：290 nM）和IL-8（IC50：320 nM）的產(chǎn)生具有濃度依賴性的抑制作用。 TPCA-1對(duì)膠質(zhì)瘤細(xì)胞增殖、TNF誘導(dǎo)的RelA (p65)核轉(zhuǎn)運(yùn)及NFκB依賴性IL8基因表達(dá)均有抑制作用。TPCA-1對(duì)IFN誘導(dǎo)的基因表達(dá)有抑制效果,并完全抑制MX1和GBP1基因表達(dá),但對(duì)ISG15表達(dá)的作用很小。此外,TPCA-1對(duì)IKK-1（IC50：400 nM）和JNK3（IC50：3600 nM）也有一定抑制效果。 |
| 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 | H2O : Insoluble
Ethanol : 2.8 mg/mL (10.03 mM), Sonication is recommended.
DMSO : 1 mg/mL (3.58 mM), Sonication is recommended.
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| 關(guān)鍵字 | TPCA-1 | TPCA 1 | STAT | IκB kinase | IκB | Inhibitor | inhibit | IKK2 | IKK | IkB/IKK | IkB | I kappa B kinase | GW-683965 | GW 683965 | Apoptosis |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Cysteamine hydrochloride | Alginic acid | Flubendazole | 5-Fluorouracil | Stavudine | Dextran sulfate sodium salt (MW 4500-5500) | Tributyrin | Myricetin | L-Ascorbic acid sodium salt | L-Ascorbic acid | Sodium 4-phenylbutyrate |
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