2-氨基-6-[2-(环丙基甲氧基)-6-羟基苯基]-4-(4-哌啶基)-3-吡啶甲腈盐酸盐
中文名称 | 2-氨基-6-[2-(环丙基甲氧基)-6-羟基苯基]-4-(4-哌啶基)-3-吡啶甲腈盐酸盐 |
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中文同义词 | 2-氨基-6-[2-(环丙基甲氧基)-6-羟基苯基]-4-(4-哌啶基)-3-吡啶甲腈盐酸盐;化合物ACHP HYDROCHLORIDE;IKK-2 抑制剂 VIII;2-氨基-6-(2-(环丙基甲氧基)-6-羟基苯基)-4-(哌啶-4-基)烟腈盐酸盐 |
英文名称 | 2-Amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridinecarbonitrile hydrochloride |
英文同义词 | 2-Amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridinecarbonitrile hydrochloride;Bayer IKK-beta inhibitor;IKK-2 inhibitor VIII;IKK-beta inhibitor;3-Pyridinecarbonitrile, 2-aMino-6-[2-(cyclopropylMethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-, hydrochloride (1:1);ACHP (Hydrochloride );2-amino-6-[2-(cyclopropylmethoxy)-6-oxocyclohexa-2,4-dien-1-ylidene]-4-piperidin-4-yl-1H-pyridine-3-carbonitrile;(6Z)-2-amino-6-[2-(cyclopropylmethoxy)-6-oxocyclohexa-2,4-dien-1-ylidene]-4-piperidin-4-yl-1H-pyridine-3-carbonitrile |
CAS号 | 406209-26-5 |
分子式 | C21H25ClN4O2 |
分子量 | 400.91 |
EINECS号 | |
相关类别 | |
Mol文件 | 406209-26-5.mol |
结构式 |
2-氨基-6-[2-(环丙基甲氧基)-6-羟基苯基]-4-(4-哌啶基)-3-吡啶甲腈盐酸盐 性质
储存条件 | Store at -20°C |
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溶解度 | DMSO:50 mg/mL(124.72 mM;需要超声波) |
形态 | 粉末 |
颜色 | 米白色至黄色 |
IKK-β 8.5 nM (IC 50 ) |
IKK-α 250 nM (IC 50 ) |
ACHP Hydrochloride (Compound 4j) exhibits potent IKK-β inhibitory (IC 50 : 8.5 nM) and cellular activities (IC 50 =40 nM, in A549 cells). ACHP moderately inhibits IKK-α with an IC 50 of 250 nM but exhibits good selectivity towards other kinases, such as IKK3, Syk and MKK4 (IC 50 >20,000 nM). Moreover, ACHP demonstrates quite potent activity in various cellular assays. ACHP inhibits NF-κB-dependent reporter gene activation in TNFα-activated HEK293 cells and PMA/calcium ionophore-activated Jurkat T cells. ACHP fails to inhibit PMA-induced AP-1 activation in MRC-5 cells and PMA/calcium ionophore induced NF-κB dependent reporter gene transcription in Jurkat cells even at concentrations exceeding 10 μM. ACHP selectively interferes with the NF-κB signaling cascade by inhibition of IKK-β in living cells. ACHP inhibits the growth of these cells in a dose-dependent manner. Tax-active cell lines are more susceptible to ACHP than Tax-inactive cell lines and Jurkat (IC 50 values in Tax-active cell lines, Tax-inactive cell lines or Jurkat are 3.1±1.3 μM, 10.7±1.7 μM and 23.6 μM, respectively), suggesting that the growth of Tax-active cells depends on NF-κB more than Tax-inactive cells.
ACHP (Compound 4j) is orally bioavailable in mice and rats and demonstrates significant in vivo activity in anti-inflammatory models (arachidonic acid-induced mouse ear edema model). ACHP has reasonable aqueous solubility (0.12 mg/mL in pH 7.4 isotonic buffer) and excellent Caco-2 permeability (P app 62.3×10 -7 cm/s), and demonstrates orally bioavailability in mice (BA: 16%) and rats (BA: 60%). The favourable bioavailability of ACHP in rats is likely due to its low clearance (0.33 L/h/kg). In an acute inflammation model, ACHP exhibits oral efficacy at 1 mg/kg in a dose-dependent manner.
安全信息
更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
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2024/08/19 | HY-13060 | ACHP Hydrochloride | 1 mg | 745元 | |
2024/08/19 | HY-13060 | 2-氨基-6-[2-(环丙基甲氧基)-6-羟基苯基]-4-(4-哌啶基)-3-吡啶甲腈盐酸盐 ACHP Hydrochloride | 406209-26-5 | 5mg | 1368元 |