TPCA-1 化学構造
分子量: 279.29

高品質保証

カスタマーフィードバック(2)

Quality Control & MSDS

製品説明

  • Compare IκB/IKK Inhibitors
    IκB/IKK製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 TPCA-1は、IKK-2の阻害剤で、IC50 が 17.9 nMです。
ターゲット IKK-2
IC50 17.9 nM [1]
In vitro試験 In a time-resolved fluorescence resonance energy transfer assay, TPCA-1 inhibits human IKK-2 activity with an IC50 of 17.9 nM. In addition, TPCA-1 is demonstrated to be ATP-competitive. Besides, TPCA-1 exhibits IC50 values of 400 nM and 3600 nM against IKK-1 and JNK3, respectively. TPCA-1 inhibits the production of TNF-α, IL-6, and IL-8 in a concentration-dependent manner, exhibiting IC50 values of 170, 290, and 320 nM, respectively. [1] TPCA-1 inhibits glioma cell proliferation, as well as TNF-induced RelA (p65) nuclear translocation and NFκB-dependent IL8 gene expression. Importantly, TPCA-1 inhibits IFN-induced gene expression, completely suppressing MX1 and GBP1 gene expression, while having only a minor effect on ISG15 expression. [2]
In vivo試験 Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg, i.p., b.i.d., results in a dose-dependent reduction in the severity of murine collagen-induced arthritis (CIA). The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg, i.p., b.i.d. are comparable to the effects of the antirheumatic drug, etanercept, when administered prophylactically at 4 mg/kg, i.p., every other day. Nuclear localization of p65, as well as levels of IL-1beta, IL-6, TNF-alpha, and interferon-gamma, is significantly reduced in the paw tissue of TPCA-1- and etanercept-treated mice. In addition, administration of TPCA-1 in vivo results in significantly decreased collagen-induced T cell proliferation ex vivo. Therapeutic administration of TPCA-1 at 20 mg/kg, but not at 3 or 10 mg/kg, i.p., b.i.d., significantly reduces the severity of CIA, as does etanercept administration at 12.5 mg/kg, i.p., every other day. [1]
臨床試験
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

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.

細胞アッセイ: [2]

細胞株 U87, MT330, SJ-G2, and GBM6 human glioma lines
濃度 0-50 μM
反応時間 3 days
実験の流れ 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.

動物実験: [1]

動物モデル Murine collagen-induced arthritis
製剤 0.9% DMSO, 7% dimethylacetoacetamide (DMA), and 10% Cremophor El
投薬量 3, 10, or 20 mg/kg
投与方法 Administered via i.p. or b.i.d.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download TPCA-1 SDF
分子量 279.29
化学式

C12H10FN3O2

CAS No. 507475-17-4
保管 2年-20℃
6月-80℃in solvent
別名 GW683965
溶解度 (25°C) * In vitro DMSO 56 mg/mL (200.5 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 2% Cremophor EL, 2% N,N-dimethylacetamide 15 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 3-Thiophenecarboxamide, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-

文献中の引用 (5)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related IκB/IKK 阻害剤

  • WS3

    WS3 is a β cell proliferation inducer via modulation of Erb3 binding protein-1 (EBP1) and the IκB kinase pathway.

  • LY2409881

    LY2409881 is a potent and selective IKK2 inhibitor with IC50 of 30 nM, >10-fold selectivity over IKK1 and other common kinases.

  • AZD3264

    AZD3264 is a novel IKK2 inhibitor.

  • BAY 11-7082

    Bay 11-7082は、IκBα によるリン酸化の阻害剤で、IC50 が10μMです。

  • IKK-16 (IKK Inhibitor VII)

    IKK-16 (IKK Inhibitor VII) is a selective IκB kinase (IKK) inhibitor for IKK-2, IKK complex and IKK-1 with IC50 of 40 nM, 70 nM and 200 nM, respectively.

  • BMS-345541

    BMS-345541 is a highly selective inhibitor of the catalytic subunits of IKK-2 and IKK-1 with IC50 of 0.3 μM and 4 μM, respectively.

  • Bardoxolone Methyl

    Bardoxolone Methyl is an IKK inhibitor, showing potent proapoptotic and anti-inflammatory activities. Phase 3.

    Features:The only IKKβ inhibitor in clinical use for solid tumors, type 2 diabetes, and chronic kidney disease. An orally-available antioxidant inflammation modulator.

  • IMD 0354

    IMD 0354 is an IKKβ inhibitor and blocks IκBα phosphorylation in NF-κβ pathway.

  • Bay 11-7085

    BAY 11-7085 is an irreversible inhibitor of TNFα-induced IκBα phosphorylation with IC50 of 10 μM.

最近チェックしたアイテム

Tags: TPCA-1を買う | TPCA-1供給者 | TPCA-1を購入する | TPCA-1費用 | TPCA-1生産者 | オーダーTPCA-1 | TPCA-1代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ