现货大促销,价格低至8折起,量大更优惠,详细咨询客服
全部分类
全部分类
  • IKK-2 inhibitor VIII
IKK-2 inhibitor VIII的可视化放大

IKK-2 inhibitor VIII

IKK-2 inhibitor VIII (IKK-2 Inhibitor VIII) 是一种高效和选择性的 IKK-β抑制剂,IC50 为 8.5 nM。

原价
¥1850-10925
价格
1480-8740
IKK-2 inhibitor VIII的二维码

所有产品仅用于科学研究,我们不为任何个人用途提供产品和服务

询价有惊喜,量大更优惠 点击这里给我发消息

  • 库存: 现货
可选包装 >>>
首页
  • 货号: ajci7258
  • CAS: 406209-26-5
  • 别名: 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,IKK-beta inhibitor
  • 分子式: C21H25ClN4O2
  • 分子量: 400.9
  • 纯度: >98%
  • 溶解度: Soluble in DMSO
  • 储存: Store at -20°C
  • 库存: 现货

Background

ACHP Hydrochloride is a highly potent and selective IKK-β inhibitor with an IC50 of 8.5 nM.

ACHP (Compound 4j) exhibits potent IKK-β inhibitory (IC50: 8.5 nM) and cellular activities (IC50=40 nM, in A549 cells). ACHP moderately inhibits IKK-α with an IC50 of 250 nM but exhibits good selectivity towards other kinases, such as IKK3, Syk and MKK4 (IC50>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[1]. 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 (IC50 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[2].
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 (Papp 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[1].

Reference:
[1]. Murata T, et al. Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 3: Orally active anti-inflammatory agents. Bioorg Med Chem Lett. 2004 Aug 2;14(15):4019-22.
[2]. Sanda T, et al. Induction of cell death in adult T-cell leukemia cells by a novel IkappaB kinase inhibitor. Leukemia. 2006 Apr;20(4):590-8.

Protocol

Cell experiment:

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 a HTLV-1-negative T-cell leukemia cell line Jurkat are used in this study. Approximately 1.5×104 cells are cultured in 96-well plate 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 multiplate reader. Cell viability (%) is calculated[2].

Animal experiment:

Mice[1]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.

参考文献:

[1]. Murata T, et al. Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 3: Orally active anti-inflammatory agents. Bioorg Med Chem Lett. 2004 Aug 2;14(15):4019-22.
[2]. Sanda T, et al. Induction of cell death in adult T-cell leukemia cells by a novel IkappaB kinase inhibitor. Leukemia. 2006 Apr;20(4):590-8.

动态评分

0.0

没有评分数据
没有评价数据
一键回到顶部
展开 收缩
安捷凯在线客服