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4-[4-[(5-硝基-2-呋喃基)亚甲基]-3,5-二氧代-1-吡唑烷基]苯甲酸乙酯

用途

PYR-41 是一种特异的,细胞可透过的 E1 抑制剂,IC50 值 < 10 μM。

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名称

[ CAS 号 ]:
418805-02-4

[ 中文名 ]:
4-[4-[(5-硝基-2-呋喃基)亚甲基]-3,5-二氧代-1-吡唑烷基]苯甲酸乙酯

[ 英文名 ]:
PYR-41

[英文别名 ]:

PYR-41

生物活性

[ 描述 ]:

PYR-41 是一种特异的,细胞可透过的 E1 抑制剂,IC50 值 < 10 μM。

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> E1/E2/E3酶

研究领域 >> 癌症

[ 靶点 ]

IC50: < 10 μM (E1)

[体外研究]

除阻断泛素化外,PYR-41还增加细胞中的总SUMO化。 PYR-41减弱细胞因子介导的核因子-κB活化。 PYR-41还可以防止IκBα的下游泛素化和蛋白酶体降解。此外,PYR-41抑制p53的降解并激活该肿瘤抑制因子的转录活性[1]。 PYR-41(50μM)促进泛素化蛋白质的积累。 PYR-41在4小时后引起Z138细胞中DUB活性的浓度依赖性(10-50μM)下降。即使在最低浓度(10μM)下,PYR-41也有效抑制USP5 DUB活性。 PYR-41有效(10-50μM)抑制各种DUB的活性,确定代表USP9x,USP5,USP14,UCH37和UCH-L3。用DTT和PYR-41共同处理Z138细胞完全消除了泛素化蛋白的积累[2]。

[激酶实验]

将兔或小鼠E1（apper 250ng）与32P-遍在蛋白在1x反应缓冲液[50mM Tris（pH 7.4），0.2mM ATP，0.5mM MgCl 2]中在室温下孵育15分钟。在一些实验中，His标记的小鼠E1在进行温育和反应之前与TALON钴亲和树脂结合。将小鼠E1和32P-遍在蛋白加入到1x反应缓冲液中的珠子中，并如E1反应一样温育。将样品在非还原性SDS-PAGE样品缓冲液中加热，并通过SDS-PAGE分离。具有遍在蛋白的硫酯通过Storm PhosphoImager可视化。

[参考文献]

[1]. Yang Y, et al. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472-81.

[2]. Kapuria V, et al. Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity. Biochem Pharmacol. 2011 Aug 15;82(4):341-9.

[相关活性小分子]

银杏酸C15:1 | NSC232003 | CC122 | SZL P1-41 | TAK-243 | DKM 2-93 | PRT4165 | Skp2抑制剂C1 | TZ9 | CC0651 | 2-D08 | PYZD-4409 | CC-885 | COH000

物理化学性质

[ 密度 ]:
1.5±0.1 g/cm3

[ 分子式 ]:
C₁₇H₁₃N₃O₇

[ 分子量 ]:
371.301

[ 精确质量 ]:
371.075348

[ PSA ]:
134.67000

[ LogP ]:
2.87

[ 外观性状 ]:
red to brown

[ 折射率 ]:
1.652

[ 储存条件 ]:
?20°C

[ 水溶解性 ]:
Soluble in DMSO at 5mg/ml with warming

MSDS

详细MSDS(安全技术说明书)

安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302-H317

[ 警示性声明 ]:
P280

[ 危害码 (欧洲) ]:
Xn

[ 风险声明 (欧洲) ]:
22-43

[ 安全声明 (欧洲) ]:
36/37

[ 危险品运输编码 ]:
NONH for all modes of transport

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