| 名称 | ACHP Hydrochloride |
| 描述 | ACHP Hydrochloride (IKK-2 Inhibitor VIII) is a highly potent and selective IKK-β inhibitor with an IC50 of 8.5 nM. |
| 细胞实验 | HTLV-1-infected T-cell lines, ATL-35T, 81-66/45, MJ, and MT-2 cells, human ATL cell lines established from ATL patients, ATL-102, ED-40515(?) and TL-Om1 cells, and an HTLV-1-negative T-cell leukemia cell line Jurkat are used in this study. Approximately 1.5×10^4 cells are cultured in 96-well plates in triplicates at 37°C. Growth inhibitory effect of ACHP (0.01, 0.1, 1, 5, 10, 50 and 100 μM) is determined using MTT assay. Optical densities (OD) at 570 and 630?nm are measured with a multi-plate reader. Cell viability (%) is calculated [2]. |
| 动物实验 | In vivo arachidonic acid-induced ear edema in mice: ear edema is induced by topical application of arachidonic acid (500 μg/ear). ACHP (0.3, 1 and 3 mg/kg, p.o.), Dexamethasone, and vehicle (10% cremophor in saline) are given po 60 min before the arachidonic acid application. Ear thickness is measured at 0, 1, 3, and 6 h after the arachidonic acid application [1]. |
| 体外活性 | ACHP Hydrochloride展现出强效的IKK-β抑制作用（IC50：8.5 nM），以及显著的细胞内活性（IC50：40 nM，在A549细胞中）。ACHP对IKK-α具有适度抑制效果（IC50为250 nM），但对其他激酶如IKK3、Syk和MKK4则表现出良好的选择性（IC50>20,000 nM）。此化合物能抑制TNFα激活的HEK293细胞和PMA/钙离子载体激活的Jurkat T细胞中NF-κB依赖性报告基因的激活。然而在超过10μM的浓度下，ACHP未能抑制MRC-5细胞中PMA诱导的AP-1激活，也未能抑制Jurkat细胞中PMA/钙离子载体诱导的NF-κB依赖性报告基因转录。ACHP通过抑制活细胞中的IKK-β选择性干预NF-κB信号通路[1]。此化合物以剂量依赖方式抑制这些细胞的生长。Tax活跃细胞系对ACHP的敏感度高于Tax非活跃细胞系及Jurkat细胞（Tax活跃、非活跃细胞系或Jurkat细胞的IC50值分别为3.1±1.3μM、10.7±1.7μM和23.6μM），这表明Tax活跃细胞的生长更依赖NF-κB[2]。 |
| 体内活性 | ACHP在小鼠和大鼠体内具有可口服和生物利用度，并在抗炎模型中显示出显著的体内活性（花生四烯酸引起的小鼠耳肿炎模型）。ACHP在水中具有合理的溶解度（在pH 7.4的等渗缓冲液中为0.12 mg/mL）和优秀的Caco-2透过性（Papp 62.3×10^-7 cm/s）。ACHP在大鼠中的良好生物利用度可能归因于其低清除率（0.33 L/h/kg）。在急性炎症模型中，ACHP以1 mg/kg的剂量依赖性方式表现出口服有效性[1]。 |
| 存储条件 | Store under nitrogen,
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.99 mM), Sonication is recommended.
DMSO : 45 mg/mL (112.25 mM), Sonication is recommended.
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| 关键字 | IκB kinase | IκB | Inhibitor | inhibit | IKKβ | IKKα | IKK | IkB/IKK | IkB | I kappa B kinase | ACHP Hydrochloride | ACHP |
| 相关产品 | GSK8612 | Rosmarinic acid | Amlexanox | Peramivir Trihydrate | Dehydrocostus Lactone | Malachite green oxalate | Resveratrol | Allicin | CCCP | MRT 67307 dihydrochloride | Abietic Acid | Vinpocetine |
| 相关库 | 抑制剂库 | 抗乳腺癌化合物库 | 经典已知活性库 | 抗癌化合物库 | 已知活性化合物库 | 激酶抑制剂库 | 抗纤维化化合物库 | 抗衰老化合物库 | 抗卵巢癌化合物库 | 免疫/炎症分子化合物库 | NF-κB 通路分子库 | 共价抑制剂库 |