TPCA-1

製品コードS2824 バッチS282404

印刷

化学情報

Synonyms

GW683965

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₂H₁₀FN₃O₂S

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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	2% Cremophor EL 1 2% N 2 N-dimethylacetamide この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	15.000mg/ml (53.71mM)
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.500mg/ml (8.95mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

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.
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, this compound is demonstrated to be ATP-competitive. Besides, it exhibits IC50 values of 400 nM and 3600 nM against IKK-1 and JNK3, respectively. This chemical 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] It inhibits glioma cell proliferation, as well as TNF-induced RelA (p65) nuclear translocation and NFκB-dependent IL8 gene expression. Importantly, this compound 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 this compound at 10 mg/kg, i.p., b.i.d. are comparable to the effects of the antirheumatic drug, 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 this compound-treated mice. In addition, administration of this chemical in vivo results in significantly decreased collagen-induced T cell proliferation ex vivo. Therapeutic administration of this compound at 20 mg/kg, but not at 3 or 10 mg/kg, i.p., b.i.d., significantly reduces the severity of CIA. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	IKK-2 Assay
キナーゼアッセイ	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 this compound or 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 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	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.

参考

https://pubmed.ncbi.nlm.nih.gov/15316093/
https://pubmed.ncbi.nlm.nih.gov/22509977/
https://pubmed.ncbi.nlm.nih.gov/24401319/

カスタマーフィードバック

: 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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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Targeting synergetic endothelial inflammation by inhibiting NFKB and JAK-STAT pathways [ iScience, 2025, 28(9):113307]	PubMed: 40894883
Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis [ Sci Adv, 2025, 11(4):eadq2395]	PubMed: 39841821
NF-κB signaling directs a program of transient amplifications at innate immune response genes [ bioRxiv, 2025, 2025.03.11.641929]	PubMed: 40161744
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
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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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