4-[N-(2',5'-二羟基苄基)氨基]苯甲酸甲酯

• 常用名: 4-[N-(2',5'-二羟基苄基)氨基]苯甲酸甲酯
• 英文名: Tyrphostin AG 957
• CAS号: 140674-76-6
• 分子量: 273.28400
• 密度: N/A
• 沸点: N/A
• 分子式: C₁₅H₁₅NO₄
• 熔点: N/A
• 闪点: N/A

用途

AG957(Tyrphostin AG957；NSC 654705)是一种酪氨酸激酶抑制剂,具有抗BCR/ABL酪氨酸激酶活性[1][2]。AG957是一种bcr/abl激酶抑制剂,p210bcr/abl自激酶活性的IC50为2.9μM[3]。

名称

• 中文名: 4-[N-(2',5'-二羟基苄基)氨基]苯甲酸甲酯
• 英文名: methyl 4-[(2,5-dihydroxyphenyl)methylamino]benzoate

生物活性

• 描述: AG957(Tyrphostin AG957；NSC 654705)是一种酪氨酸激酶抑制剂,具有抗BCR/ABL酪氨酸激酶活性[1][2]。AG957是一种bcr/abl激酶抑制剂,p210bcr/abl自激酶活性的IC50为2.9μM[3]。
• 相关类别:
  研究领域 >> 癌症
  信号通路 >> 蛋白酪氨酸激酶 >> BCR-ABL
• 体外研究: AG957抑制p210bcr abl酪氨酸激酶活性。AG957可在2小时内抑制DNA合成(20微米时抑制率为60%)。AG957抑制活细胞中p210bcr abl酪氨酸磷酸化1小时,而不抑制总蛋白磷酸化[1]。酪磷蛋白AG957是一种蛋白酪氨酸激酶(PTK)抑制剂,具有对抗p210BCR/ABL激酶的活性,对CML祖细胞中β1整合素功能有影响[2]。AG957(0.1-100μM)预处理可显著抑制慢性粒细胞白血病(CML)集落形成细胞(CFC)CML CFC的增殖[2]。AG957(25μM)部分抑制几种蛋白质的磷酸化,这些蛋白质是BCR/ABL PTK底物,参与BCR/ABL表达细胞中的正常整合素信号[2]。细胞增殖试验[2]细胞系：CML和CFC浓度：0,0.1,1,10,100μM培养时间：预处理1小时结果：在与AG957预培养后,CML CFC生长受到明显的剂量依赖性抑制。Western Blot分析[2]细胞系：K562和BCR/ABL转染的M07e细胞(MBA-4)浓度：25μM培养时间：24小时结果：部分抑制K562细胞中p210BCR/ABL、粘着蛋白paxillin、PI3K的p85调节亚单位和适配蛋白cbl的酪氨酸磷酸化。抑制这些蛋白质的磷酸化以及MBA4细胞中的适配蛋白crkl。
• 体内研究: AG957(10mg/kg；气管内LPS激发前1h气管内注射)阻断小鼠肺中的c-Abl活性[4]。动物模型：C57BL/6J小鼠[4]剂量：10mg/kg给药：气管内LPS激发前1h气管内给药结果：LPS诱导Y31和Y118处的帕西林显著磷酸化。AG957对c-Abl的抑制减弱了LPS诱导的两个位点的帕西林磷酸化。LPS在DMSO处理的小鼠中诱导VE钙粘蛋白显著磷酸化,而在AG957处理的小鼠中则减弱。
• 参考文献:

  [1]. G Kaur, et al. Tyrphostin induced growth inhibition: correlation with effect on p210bcr-abl autokinase activity in K562 chronic myelogenous leukemia. Anticancer Drugs. 1994 Apr;5(2):213-22.

  [2]. R Bhatia, et al. Tyrphostin AG957, a tyrosine kinase inhibitor with anti-BCR/ABL tyrosine kinase activity restores beta1 integrin-mediated adhesion and inhibitory signaling in chronic myelogenous leukemia hematopoietic progenitors. Leukemia. 1998 Nov;12(11):1708-17.

  [3]. P A Svingen, et al. Effects of the bcr/abl kinase inhibitors AG957 and NSC 680410 on chronic myelogenous leukemia cells in vitro. Clin Cancer Res. 2000 Jan;6(1):237-49.

  [4]. Panfeng Fu, et al. c-Abl mediated tyrosine phosphorylation of paxillin regulates LPS-induced endothelial dysfunction and lung injury. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1025-38.

物理化学性质

• 分子式: C₁₅H₁₅NO₄
• 分子量: 273.28400
• 精确质量: 273.10000
• PSA: 78.79000
• LogP: 2.56950
• InChIKey: QSFREBZMBNRGOK-UHFFFAOYSA-N
• SMILES: COC(=O)c1ccc(NCc2cc(O)ccc2O)cc1
• 储存条件: -20°C

安全信息

• 危害码 (欧洲): Xi

靶点实验

查看更多实验

实验名称：Luminescence-based cell-based primary high throughput screening assay to identify ago... 来源：The Scripps Research Institute Molecular Screening Center 靶标：mu-type opioid receptor isoform MOR-1 [Homo sapiens] External Id：OPRM1-OPRD1_AG_LUMI_1536_1X%ACT PRUN

实验名称：QFRET-based biochemical primary high throughput screening assay to identify exosite i... 来源：The Scripps Research Institute Molecular Screening Center 靶标：disintegrin and metalloproteinase domain-containing protein 17 preproprotein [Homo sapiens] External Id：ADAM17_INH_QFRET_1536_1X%INH PRUN

实验名称：Fluorescence-based cell-based primary high throughput screening assay to identify ago... 来源：The Scripps Research Institute Molecular Screening Center 靶标：muscarinic acetylcholine receptor M1 [Homo sapiens] External Id：CHRM1_AG_FLUO8_1536_1X%ACT PRUN

实验名称：Fluorescence polarization to screen for inhibitor that competite the binding of FadD2... 来源：Broad Institute 靶标：FATTY-ACID-CoA LIGASE FADD28 (FATTY-ACID-CoA SYNTHETASE) External Id：2147-01_Inhibitor_SinglePoint_HTS_Activity

实验名称：Bursicon-induced LGR2 mediated cAMP production in LGR-2/CRE6x-Luciferase co-transfect... 来源：Broad Institute 靶标：N/A External Id：Bursicon-induced LGR2 mediated cAMP production in LGR-2/CRE6x-Luciferase co-transfected HEK293 cells Inhibition - 7011-01_Antagonist_SinglePoint_HTS_Activity

实验名称：Fluorescence-based cell-based primary high throughput screening assay to identify pos... 来源：The Scripps Research Institute Molecular Screening Center 靶标：muscarinic acetylcholine receptor M1 [Homo sapiens] External Id：CHRM1_PAM_FLUO8_1536_1X%ACT PRUN

实验名称：Fluorescence polarization-based biochemical high throughput primary assay to identify... 来源：The Scripps Research Institute Molecular Screening Center 靶标：RecName: Full=Sialate O-acetylesterase; AltName: Full=H-Lse; AltName: Full=Sialic acid-specific 9-O-acetylesterase; Flags: Precursor [Homo sapiens] External Id：SIAE_INH_FP_1536_1X%INH PRUN

实验名称：uHTS identification of small molecule modulators of NR3A 来源：Burnham Center for Chemical Genomics 靶标：N/A External Id：SBCCG-A1015-NR3A-Primary-Assay

实验名称：uHTS identification of small molecule modulators of Rev-erb Alpha. 来源：Burnham Center for Chemical Genomics 靶标：N/A External Id：SBCCG-A1016-RevErbaLBD-Primary-Assay

实验名称：MITF Measured in Cell-Based System Using Plate Reader - 2084-01_Activator_SinglePoint... 来源：Broad Institute 靶标：N/A External Id：2084-01_Activator_SinglePoint_HTS_Activity

共97条，当前第1页，共10页

1

2

3

4

5

英文别名

• N-(2,5-dihydroxylbenzyl)-4-methoxycarbonyl aniline
• methyl 4-(N-2,5-dihydroxybenzylamino)benzoate
• AG 957
• 4-Amino-N-(2,5-dihydroxybenzyl)methyl benzoate
• Tyrphostin AG 957
• Benzoic acid,4-[[(2,5-dihydroxyphenyl)methyl]amino]-,methyl ester
• methyl 4-[(2,5-dihydroxybenzyl)amino]benzoate