中文名 | ACHP (Hydrochloride ) |
英文名 | ACHP (Hydrochloride ) |
别名 | IKK-2 抑制剂 VIII 化合物ACHP HYDROCHLORIDE 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 |
英文别名 | IKK-beta inhibitor IKK-2 inhibitor VIII ACHP (Hydrochloride ) ACHP (Hydrochloride ) Bayer IKK-beta inhibitor 2-Amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridinecarbonitrile 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 | 406209-26-5 |
化学式 | C21H25ClN4O2 |
分子量 | 400.9018 |
溶解度 | 10毫米DMSO |
存储条件 | -20℃ |
体外研究 | 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. |
体内研究 | 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. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.494 ml | 12.472 ml | 24.944 ml |
5 mM | 0.499 ml | 2.494 ml | 4.989 ml |
10 mM | 0.249 ml | 1.247 ml | 2.494 ml |
5 mM | 0.05 ml | 0.249 ml | 0.499 ml |
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