EBE-A22
(Synonyms: N-(3-溴苯基)-6,7-二甲氧基-N-甲基-4-喹唑啉胺) 目录号 : GC35959EBE-A22 is a derivative of PD 153035 which can inhibit ErbB-1-phosphorylation, whereas EBE-A22 is inactive.
Cas No.:229476-53-3
Sample solution is provided at 25 µL, 10mM.
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EBE-A22 is a derivative of PD 153035 which can inhibit ErbB-1-phosphorylation, whereas EBE-A22 is inactive.
[1] Thomas W Grunt, et al. J Cell Physiol . 2007 Jun;211(3):803-15.
Cas No. | 229476-53-3 | SDF | |
别名 | N-(3-溴苯基)-6,7-二甲氧基-N-甲基-4-喹唑啉胺 | ||
Canonical SMILES | BrC1=CC(N(C)C2=NC=NC3=CC(OC)=C(OC)C=C23)=CC=C1 | ||
分子式 | C17H16BrN3O2 | 分子量 | 374.23 |
溶解度 | DMSO: 50 mg/mL (133.61 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.6722 mL | 13.3608 mL | 26.7215 mL |
5 mM | 0.5344 mL | 2.6722 mL | 5.3443 mL |
10 mM | 0.2672 mL | 1.3361 mL | 2.6722 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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DNA interaction of the tyrosine protein kinase inhibitor PD153035 and its N-methyl analogue
Biochemistry 2001 Apr 17;40(15):4663-71.PMID:11294633DOI:10.1021/bi002777a.
The brominated anilinoquinazoline derivative PD153035 exhibits a very high affinity and selectivity for the epidermal growth factor receptor tyrosine kinase (EGF-R TK) and shows a remarkable cytotoxicity against several types of tumor cell lines. In contrast, its N-methyl derivative, designated EBE-A22, has no effect on EGF-R TK but maintains a high cytotoxic profile. The present study was performed to explore the possibility that PD153035 and its N-methyl analogue might interact with double-stranded DNA, which is a primary target for many conventional antitumor agents. We studied the strength and mode of binding to DNA of PD153035 and EBE-A22 by means of absorption, fluorescence, and circular and linear dichroism as well as by a relaxation assay using human DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to show that both drugs bind to DNA and behave as typical intercalating agents. In particular, EBE-A22 unwinds supercoiled plasmid, stabilizes duplex DNA against heat denaturation, and produces negative CD and ELD signals, as expected for an intercalating agent. Extensive DNase I footprinting experiments performed with a large range of DNA substrates show that EBE-A22, but not PD153035, interacts preferentially with GC-rich sequences and discriminates against homooligomeric runs of A and T which are often cut more readily by the enzyme in the presence of the drug compared to the control. Altogether, the results provide the first experimental evidence that DNA is a target of anilinoquinazoline derivatives and suggest that this N-methylated ring system is a valid candidate for the development of DNA-targeted cytotoxic compounds. The possible relevance of selective DNA binding to activity is considered. The unexpected GC-selective binding properties of EBE-A22 entreat further exploration into the use of N-methylanilinoquinazoline derivatives as tools for designing sequence-specific DNA binding ligands.
Upregulation of retinoic acid receptor-beta by the epidermal growth factor-receptor inhibitor PD153035 is not mediated by blockade of ErbB pathways
J Cell Physiol 2007 Jun;211(3):803-15.PMID:17286282DOI:10.1002/jcp.20990.
Inhibiting epidermal growth factor-receptor (ErbB-1) represents a powerful anticancer strategy. Activation of retinoid pathways is also in development for cancer treatment. Retinoic acid receptor-beta-the tumor suppressor and main retinoid mediator--is silenced in many tumors. The ErbB-1 inhibitor PD153035 cooperates with retinoic acid during growth inhibition and induces retinoic acid receptor-beta suggesting that ErbB-1 controls retinoic acid receptor-beta. However, here we demonstrate that ErbB pathways are not involved in PD153035-mediated retinoic acid receptor-beta-upregulation. PD153035 inhibits ErbB-1-phosphorylation, whereas its derivative EBE-A22 is inactive. Yet both inhibit cell growth and upregulate retinoic acid receptor-beta in ErbB-1-overexpressing (MDA-MB-468), moderately expressing (OVCAR-3), ErbB-1-negative (MDA-MB-453) or ErbB-negative cells (CEM, Jurkat). Both bind DNA, whereas the closely related ErbB-1 inhibitors AG1478 and ZD1839, which are inactive on retinoic acid receptor-beta, do not significantly bind DNA. None of the other ErbB-1/ErbB-2 inhibitors tested (RG-14620, LFM-A12, AG879, AG825) affect retinoic acid receptor-beta. PD153035 decreases methylation of the retinoic acid receptor-beta2 promoter. In OVCAR-3, it stimulates dislodgement of histone deacetylase 1 from the promoter and acetylation of histones H3 and H4. Consequently, PD153035 facilitates recruitment of RNA polymerase II to the promoter and stimulates transcriptional activity. Moreover, PD153035 increases the retinoic acid receptor-beta mRNA half-life. No other retinoid receptor, nor estrogen receptor-alpha, nor RASSF1A is upregulated by PD153035. Thus PD153035 induces retinoic acid receptor-beta by ErbB-independent transcriptional and post-transcriptional mechanisms. This report highlights a triple action for an ErbB-1 inhibitor (ErbB-1 inhibition, DNA intercalation, retinoic acid receptor-beta-induction). Such multitargeting drugs bear great potential for cancer treatment.