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AS 602801

现货
Catalog No.
A3189
Jun激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,450.00
现货
10mg
¥ 2,560.00
现货
50mg
¥ 4,110.00
现货
200mg
¥ 11,310.00
现货
500mg
¥ 20,570.00
现货

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Background

Kinases represent one of the most popular and promising target class in drug discovery. Success in finding new therapeutics will depend on the validation of the kinase chosen with respect to the disease of interest, and on the ability of chemists to design and synthesize inhibitors. AS602801 is a potent and selective JNK inhibitor with therapeutic potential inMS and fibrosis.

In vitro: AS602801 blocked T-lymphocyte proliferation and induced apoptosis. In RRMS CD4t and CD8t cells, AS602801 induced apoptosis genes and expression of surface markers, while in RRMS CD11bt cells it induced expression of innate immunity receptors and co-stimulatory molecules [1].

In vivo: AS602801, the best JNK inhibitors identified so far, were currently evaluated in preclinical studies, based on preliminary promising results in animal model of auto-immune diseases and neuronal apoptosis [1].

Clinical trial: Recently, a phase IIa proof of concept study of the pan-JNK inhibitor bentamapimod (PGL5001, AS602801) for the treatment of inflammatory endometriosis had been terminated.

Reference:
[1] Ferrandi C, Richard F, Tavano P, Hauben E, Barbié V, Gotteland JP, Greco B, Fortunato M, Mariani MF, Furlan R, Comi G, Martino G, Zaratin PF.  Characterization of immune cell subsets during the active phase of multiple sclerosis reveals disease and c-Jun N-terminal kinase pathway biomarkers. Mult Scler. 2011;17(1):43-56.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt457.55
Cas No.848344-36-5
FormulaC25H23N5O2S
SynonymsBentamapimod;AS602801;AS-602801
Solubility≥11.45mg/mL in DMSO, <2.87 mg/mL in EtOH, <2.85 mg/mL in H2O
Chemical Name2-(benzo[d]thiazol-2-yl)-2-(2-((4-(morpholinomethyl)benzyl)oxy)pyrimidin-4-yl)acetonitrile
SDFDownload SDF
Canonical SMILESN#CC(C1=NC(OCC2=CC=C(C=C2)CN3CCOCC3)=NC=C1)C4=NC5=CC=CC=C5S4
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

酶学实验 1]:

激酶检测

在10 uM ATP,2.5 uCi [γ-32P] ATP和底物的存在下,将纯化的激酶结构域与AS602801(100 uM~0.006 uM,两倍稀释液或空白(0.1%DMSO)温育。通过在硝酸纤维素膜上点样来终止反应。然后将膜洗涤四次以除去未结合的放射性并干燥。通过荧光成像定量转移的放射性,S型拟合计算IC50值。

细胞实验 [2]:

细胞系

PANC-1、A549和A2780细胞系

溶解方法

在DMSO中的溶解度>11.5 mg/mL。为了获得更高浓度,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

7.5 μM,3天

应用

AS602801对肿瘤细胞具有选择性细胞毒活性,具有抗癌作用。AS602801可诱导三种血清培养的人类癌细胞系(PANC-1,胰腺癌;A594,肺癌;A2780,卵巢癌)死亡,减少活细胞数。

动物实验 [2]:

动物模型

BALB/cAJcl-nu/nu小鼠异种移植模型(PANC-1 CSLCs (原发性肿瘤))

剂量

腹膜内注射,每天40 mg/kg,连续10天。

应用

AS602801治疗降低原发性肿瘤((PANC-1 CSLCs))小鼠中肿瘤起始细胞的比例。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Olusegun Williams, et al. Discovery of dual inhibitors of the immune cell PI3Ks p110δ and p110γ: a prototype for new anti-inflammatory drugs. Chem Biol. 2010 Feb 26; 17(2): 123–134.

[2] Masashi Okada, et al. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10; 7(19): 27021–27032.

质量控制

化学结构

AS 602801