受注:045-509-1970 |
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Synonyms | GW683965 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C12H10FN3O2S |
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分子量 | 279.29 | CAS No. | 507475-17-4 | ||||
Solubility (25°C)* | 体外 | DMSO | 56 mg/mL (200.5 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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. |
製品説明 | TPCA-1 (GW683965) is an inhibitor of IKK-2 with IC50 of 17.9 nM in a cell-free assay, inhibits NF-κB pathway, exhibits 22-fold selectivity over IKK-1. TPCA-1 is also an inhibitor of STAT3 and enhances apoptosis. |
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in vitro | 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 | 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] |
キナーゼアッセイ | IKK-2 Assay | |
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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 | 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. |
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動物実験 | 動物モデル | Murine collagen-induced arthritis |
投薬量 | 3, 10, or 20 mg/kg | |
投与方法 | Administered via i.p. or b.i.d. |
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Data from [Mol Cancer, 2014, 13, 40]
, , J Cell Mol Med, 2017, 21(7):1373-1387
Data from [Data independently produced by , , Oncogene, 2016, 35(31):4036-47]
Tumor cell senescence-induced macrophage CD73 expression is a critical metabolic immune checkpoint in the aging tumor microenvironment [ Theranostics, 2024, 14(3):1224-1240] | PubMed: 38323313 |
Noncanonical TRAIL Signaling Promotes Myeloid-Derived Suppressor Cell Abundance and Tumor Growth in Cholangiocarcinoma [ Cell Mol Gastroenterol Hepatol, 2024, S2352-345X(24)00005-5] | PubMed: 38219900 |
Myeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB [ Nat Commun, 2023, 14(1):8082] | PubMed: 38057310 |
A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner [ Cell Death Differ, 2023, 10.1038/s41418-023-01141-0] | PubMed: 36869180 |
CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway [ Pharmaceuticals (Basel), 2023, 16(9)1210] | PubMed: 37765018 |
Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation [ Respir Res, 2023, 24(1):90] | PubMed: 36949482 |
CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway [ Pharmaceuticals (Basel), 2023, 16(9)1210] | PubMed: 37765018 |
TRAF6-TAK1-IKKβ pathway mediates TLR2 agonists activating "one-step" NLRP3 inflammasome in human monocytes [ Cytokine, 2023, 169:156302] | PubMed: 37480791 |
Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal cancers [ Research Square, 2023, ] | PubMed: none |
A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis [ Nat Cell Biol, 2022, 24(5):766-782] | PubMed: 35501370 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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