5,6-双(苯基氨基)异吲哚啉-1,3-二酮

5,6-双(苯基氨基)异吲哚啉-1,3-二酮用途

CGP52411 (DAPH) 是一种高选择性,有效,口服活性和 ATP 竞争性的 EGFR 抑制剂,IC50 为 0.3 μM。CGP52411 阻止有毒的 Ca2+ 离子流入神经元细胞,并显着抑制和逆转与阿尔茨海默症相关的 β-amyloid (Aβ42) 原纤维聚集物的形成。

5,6-双(苯基氨基)异吲哚啉-1,3-二酮名称

[ CAS 号 ]:
145915-58-8

[ 中文名 ]:
4,5-二苯胺基酞酰亚胺

[ 英文名 ]:
CGP 52411

[英文别名 ]:

5,6-bis-phenylamino-isoindole-1,3-dione
DAPH-1
4,5-dianilinophthalimide
DAPH
5,6-bis-phenylamino-isoindole-1,3-dione,DAPH

5,6-双(苯基氨基)异吲哚啉-1,3-二酮生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 癌症

信号通路 >> JAK/STAT信号通路 >> EGFR

信号通路 >> 蛋白酪氨酸激酶 >> EGFR

研究领域 >> 神经疾病

[ 靶点 ]

EGFR:0.3 μM (IC50)

Amyloid-β

[体外研究]

CGP52411(DAPH；0-100μM；90分钟；A431细胞)处理抑制体外自磷酸化和c-src自磷酸化,并呈剂量依赖性,IC50s分别为1μM和16μM。CGP52411处理还显示p185c-erbB2酪氨酸磷酸化的浓度依赖性降低,IC50值为10μM[1]。cgp5241(DAPH)抑制IC50值为16μM的c-src激酶。cgp5241抑制IC50值为80μM的猪脑PKC同工酶。cgp5241抑制常规PKC同工酶(cPKCsα、β-1、β-2和γ),但不抑制非常规PKC同工酶(nPKCsδ、ε和ζ)或非典型PKC同工酶(aPKCη)[1]。Western Blot分析[1]细胞系：A431细胞浓度：0μM,0.1μM,1μM,10μM,50μM,100μM孵育时间：90分钟结果：IC50为1μM时以剂量依赖性方式抑制体外自磷酸化。IC50为16μM时抑制c-src自磷酸化,并导致p185c-erbB2酪氨酸磷酸化的浓度依赖性降低,估计IC50值为10μM。

[体内研究]

CGP52411(3.2 mg/kg、6.3 mg/kg、12.5 mg/kg、25 mg/kg和50 mg/kg；口服；每日；15天；雌性BALB/c裸鼠)体内治疗A431和SK-OV-3肿瘤的异种移植物,并具有抗肿瘤活性[1]。动物模型：雌性BALB/c裸鼠注射a431细胞[1]剂量：3.2mg/kg、6.3mg/kg、12.5mg/kg、25mg/kg、50mg/kg；口服；每日；15天结果：50mg/kg～6.3mg/kg剂量组有抗肿瘤作用。

[参考文献]

[1]. Buchdunger E, et al. 4,5-Dianilinophthalimide: a protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2334-8.

[2]. Blanchard BJ, et al. Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule. Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14326-32.

5,6-双(苯基氨基)异吲哚啉-1,3-二酮物理化学性质

[ 密度 ]:
1.374 g/cm3

[ 熔点 ]:
199-202℃

[ 分子式 ]:
C₂₀H₁₅N₃O₂

[ 分子量 ]:
329.35200

[ 精确质量 ]:
329.11600

[ PSA ]:
70.23000

[ LogP ]:
4.53220

[ 储存条件 ]:
2-8°C

5,6-双(苯基氨基)异吲哚啉-1,3-二酮MSDS

详细MSDS(安全技术说明书)

5,6-双(苯基氨基)异吲哚啉-1,3-二酮安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 安全声明 (欧洲) ]:
36/37

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

[ WGK德国 ]:
3

5,6-双(苯基氨基)异吲哚啉-1,3-二酮合成路线

详细合成路线

5,6-双(苯基氨基)异吲哚啉-1,3-二酮上下游产品

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