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6,7-二甲氧基-4-[N-(3-溴苯基)氨基]喹唑啉盐酸盐

用途

PD153035 (ZM 252868;AG 1517;Tyrphostin AG 1517;SU 5271) 是有效地 EGFR 抑制剂， K_i 和 IC₅₀ 值分别为6和25 pM。

名称

[ CAS 号 ]:
183322-45-4

[ 中文名 ]:
4-[(3-溴苯基)氨基]-6,7-二甲氧基喹唑啉盐酸盐盐

[ 英文名 ]:
PD153035 HCl

[中文别名 ]:

[英文别名 ]:

Tyrphostin AG 1517
PD-153035 HYDROCHLORIDE
PD153035 HCl
PD153035 HCL
SU-5271
AG1517
PD153035 Hydrochloride

生物活性

[ 描述 ]:

PD153035 (ZM 252868;AG 1517;Tyrphostin AG 1517;SU 5271) 是有效地 EGFR 抑制剂, Ki 和 IC50 值分别为6和25 pM。

[ 相关类别 ]:

研究领域 >> 癌症

[ 靶点 ]

EGFR:6 pM (Ki)

EGFR:25 pM (IC50)

[体外研究]

PD153035抑制A431人类表皮样癌细胞中EGF刺激的受体自身磷酸化,IC50为14 nM [1]。 PD 153035对PDGFR,FGFR,CSF-1受体,胰岛素受体或src酪氨酸激酶的影响很小,浓度高达50μM。 PD 153035在成纤维细胞或人表皮样癌细胞中以低纳摩尔浓度快速抑制EGF受体的自磷酸化,并选择性地阻断EGF介导的细胞过程,包括有丝分裂发生,早期基因表达和致癌转化[2]。 PD153035引起EGF受体阳性细胞系的剂量依赖性生长抑制,从小于微摩尔浓度开始,并且在大多数情况下IC50小于1pM [3]。

[体内研究]

单次ip剂量为80mg/kg后,血浆和肿瘤中的PD153035水平在15分钟内升至50和22μM。虽然PD 153035的血浆水平在3小时内降至1μM以下,但在肿瘤中它仍保持在微摩尔浓度至少12小时。 EGF受体的酪氨酸磷酸化在肿瘤中迅速被抑制80-90％[4]。

[细胞实验]

不同的EGF受体过表达细胞系（A43 1，Difi，MDA-MB-468，MDA-MB-231，DU145，SiHa，C4i和ME18）用PD153035以0.125-2.5pM的递增浓度处理。生长抑制作用在单层细胞培养中评估[3]。

[动物实验]

小鼠：给小鼠注射PD153035（80mg / kg）或载体，并在20分钟和180分钟切除谣言并制备提取物。每个时间点使用两只小鼠，并且重复实验四次。在四个实验的每一个中，ANOVA用于比较EGF刺激的PD 153035的抑制[3]。

[参考文献]

[1]. Bridges AJ, et al. Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem. 1996 Jan 5;39(1):267-76.

[2]. Fry DW, et al. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science. 1994 Aug 19;265(5175):1093-5.

[3]. Bos M, et al. PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptoractivation and inhibits growth of cancer cells in a receptor number-dependent manner. Clin Cancer Res. 1997 Nov;3(11):2099-106.

[4]. Kunkel MW, et al. Inhibition of the epidermal growth factor receptor tyrosine kinase by PD153035 in human A431 tumors in athymic nude mice. Invest New Drugs. 1996;13(4):295-302.

[相关活性小分子]

物理化学性质

[ 沸点 ]:
472.1ºC at 760 mmHg

[ 熔点 ]:
265°C(lit.)

[ 分子式 ]:
C₁₆H₁₅BrClN₃O₂

[ 分子量 ]:
396.666

[ 闪点 ]:
239.3ºC

[ 精确质量 ]:
395.003601

[ PSA ]:
56.27000

[ LogP ]:
5.02810

[ 外观性状 ]:
white to beige

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
DMSO: soluble2mg/mL, clear (warmed)

MSDS

详细MSDS(安全技术说明书)

安全信息

[ 符号 ]:

GHS05, GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H315-H318-H335

[ 警示性声明 ]:
P261-P280-P301 + P310-P305 + P351 + P338

[ 危害码 (欧洲) ]:
T

[ 风险声明 (欧洲) ]:
25-37/38-41

[ 安全声明 (欧洲) ]:
26-39-45

[ 危险品运输编码 ]:
UN 2811 6.1 / PGIII

[ 海关编码 ]:
2933990090

海关

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

文献

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