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ACHP

现货
Catalog No.
B5638
IκB激酶抑制剂
组合的产品项目
规格价格库存 数量
10mg
¥ 6,160.00
Ship with 10-15 days

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Background

IC50: 8.5 and 250 nM for IKKβ and IKKα, respectively

ACHP is an IκB kinase inhibitor. Nuclear factor-KB (NF-KB) involved in cell survival and proliferation of multiple myeloma has been well established.

In vitro: ACHP is selective for IKKα and IKKβ over IKK3, Syk and MAPKKK4 (IC50 > 20 μM), DNA binding activity of NF-κB is inhibited. ACHP is an effective blockade NF-κB pathway in multiple myeloma cell lines, and induces cell growth arrest and apoptosis. It was observed that NF-KB is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. In addition, It was found the phosphorylation of p65 subunit of NF-KB besides the phosphorylation of IKBA and the activation of NF-KB DNA binding and that various target genes of NF-KB including bcl-xL, XIAP, c-IAP1, cyclin D1, and IL-6 are up-regulated. 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinenitrile (ACHP) is a novel IKB kinase inhibitor. Treatment of myeloma cells with ACHP showed the cell growth was efficiently inhibited (IC50 values ranging from 18 to 35 Mmol/L) concomitantly with inhibition of the phosphorylation of IKBA/p65 and NF-KB DNA-binding, down-regulation of the NF-KB target genes, and then induction of apoptosis. In addition, the treatment of ACHP potentiated the cytotoxic effects of vincristine and melphalan (L-phenylalanine mustard), conventional antimyeloma drugs. These findings suggest that by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of NF-KB, IKB kinase inhibitors such as ACHP can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents.

In vivo: So far, no study in vivo has been conducted.

Clinical trial: Clinical study has been conducted.

Reference:
[1] Sanda T, Iida S, Ogura H, Asamitsu K, Murata T, Bacon KB, Ueda R, Okamoto T.  Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor. Clin Cancer Res. 2005 Mar 1;11(5):1974-82.

Chemical Properties

Physical AppearanceYellow solid
StorageStore at -20°C
M.Wt364.44
Cas No.406208-42-2
FormulaC21H24N4O2
Solubility<7.29mg/ml in DMSO
Chemical Name(E)-2-amino-6-(2-(cyclopropylmethoxy)-6-oxocyclohexa-2,4-dien-1-ylidene)-4-(piperidin-4-yl)-1,6-dihydropyridine-3-carbonitrile
SDFDownload SDF
Canonical SMILESO=C1/C(C(OCC2CC2)=CC=C1)=C3NC(N)=C(C#N)C(C4CCNCC4)=C/3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

U266和NCUMM-2骨髓瘤细胞系

溶解方法

在DMSO中的溶解度> 10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0-50 μM; 8 h

应用

在U266和NCUMM-2骨髓瘤细胞系中,ACHP(>10μmol/ L)仅在4小时后即能抑制NF-κB的DNA结合活性。ACHP在1μmol/ L的浓度下治疗20分钟还能够有效抑制IκBα和p65的磷酸化。ACHP(10μmol/ L,24h)也抑制细胞周期进程并诱导细胞凋亡。在NCUMM-2细胞中,ACHP(10μmol/ L)有效诱导细胞凋亡(15.8%),较高浓度的ACHP(50μmol/ L)诱导43.7%的细胞凋亡。

References:

[1] Sanda T, Iida S, Ogura H, Asamitsu K, Murata T, Bacon KB, Ueda R, Okamoto T. Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor. Clin Cancer Res. 2005 Mar 1;11(5):1974-82.

质量控制

质量控制和MSDS

批次:

化学结构

ACHP