AG-1478
(Synonyms: Tyrphostin AG-1478; AG 1478; NSC 693255; AG1478) 目录号 : GC17226
AG-1478是一种选择性的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，其IC50值为3nM。
Cas No.:153436-53-4
Sample solution is provided at 25 µL, 10mM.
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AG-1478 is a selective EGFR tyrosine kinase inhibitor with IC50 of 3nM[1]. The transmembrane receptor tyrosine kinase (RTK) Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family, orchestrates cell signaling, growth, differentiation, survival, and migration[2]. AG-1478, as an EGFR kinase inhibitor, is commonly used in research related to inflammation, cancer, and viral infections[3-5].
In vitro, treatment of MDA-MB-231 and MCF-7 cells with serial concentrations of AG-1478(5-40μM; 72h) suppressed cellular growth by inhibiting cell proliferation, inducing apoptosis, and inhibiting telomerase activity, while also significantly down-regulating the expression of MMP-9 and inhibiting cell invasion[6]. Treatment of Nasopharyngeal Carcinoma CNE2 cells with AG-1478(0-100μM; 72h) inhibited the proliferation of CNE2 cells by inhibiting EGFR phosphorylation and the activation of downstream molecules Akt and MAPK, inducing cell cycle arrest in G1 phase, and significantly up-regulating the levels of p27 protein[7].
In vivo, ApoE-/- mice were fed a high-fat diet (HFD) for 8 weeks, followed by oral administration of AG-1478 (10mg/kg/day) for 8 weeks significantly blocked the phosphorylation of cardiac EGFR induced by the high-fat diet, and reduced myocardial inflammation, fibrosis, apoptosis and dysfunction without affecting the levels of plasma low-density lipoprotein (LDL) and total triglycerides (TG) [8].
References:
[1] Bojko A, Reichert K, Adamczyk A, Ligęza J, Ligęza J, Klein A. The effect of tyrphostins AG494 and AG1478 on the autocrine growth regulation of A549 and DU145 cells. Folia Histochem Cytobiol. 2012;50(2):186-195.
[2] Sabbah DA, Hajjo R, Sweidan K. Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors. Curr Top Med Chem. 2020;20(10):815-834.
[3] Shimizu S, Takezawa-Yasuoka K, Ogawa T, Tojima I, Kouzaki H, Shimizu T. The epidermal growth factor receptor inhibitor AG1478 inhibits eosinophilic inflammation in upper airways. Clin Immunol. 2018;188:1-6.
[4] Shushan A, Rojansky N, Laufer N, et al. The AG1478 tyrosine kinase inhibitor is an effective suppressor of leiomyoma cell growth. Hum Reprod. 2004;19(9):1957-1967.
[5] Dorobantu CM, Harak C, Klein R, et al. Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα. Antimicrob Agents Chemother. 2016;60(10):6402-6406.
[6] Zhang YG, Du Q, Fang WG, Jin ML, Tian XX. Tyrphostin AG1478 suppresses proliferation and invasion of human breast cancer cells. Int J Oncol. 2008;33(3):595-602.
[7] Zhu XF, Liu ZC, Xie BF, et al. EGFR tyrosine kinase inhibitor AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells. Cancer Lett. 2001;169(1):27-32.
[8] Li W, Fang Q, Zhong P, et al. EGFR Inhibition Blocks Palmitic Acid-induced inflammation in cardiomyocytes and Prevents Hyperlipidemia-induced Cardiac Injury in Mice. Sci Rep. 2016;6:24580.
AG-1478是一种选择性的表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，其IC50值为3nM[1]。跨膜受体酪氨酸激酶（RTK）表皮生长因子受体（EGFR）是ErbB家族的一员，协调细胞信号传导、生长、分化、存活和迁移[2]。作为EGFR激酶抑制剂，AG-1478通常用于炎症、癌症和病毒感染等相关研究[3-5]。
在体外实验中，用不同浓度的AG-1478（5-40μM；72小时）处理MDA-MB-231和MCF-7细胞，可通过抑制细胞增殖、诱导细胞凋亡和抑制端粒酶活性来抑制细胞生长，同时显著下调MMP-9的表达并抑制细胞侵袭[6]。用AG-1478（0-100μM；72小时）处理鼻咽癌CNE2细胞，可通过抑制EGFR磷酸化及其下游分子Akt和MAPK的激活，诱导细胞周期停滞在G1期，并显著上调p27蛋白的水平，从而抑制CNE2细胞的增殖[7]。
在体内实验中，对ApoE-/-小鼠进行高脂饮食（HFD）喂养8周后，再给予AG-1478（10mg/kg/天）口服治疗8周，可显著阻断高脂饮食诱导的心脏EGFR磷酸化，并减少心肌炎症、纤维化、凋亡和功能障碍，而不影响血浆低密度脂蛋白（LDL）和总甘油三酯（TG）水平[8]。
| Cell experiment [1]: | |
Cell lines | Human breast cancer cell lines MDA-MB-231 and MCF-7 |
Preparation Method | The human breast cancer cell lines MDA-MB-231 and MCF-7 were obtained from American Type Culture Collection. Cells were grow in RPMI-1640 supplemented with 10% FBS, 100U/ml penicillin and 100μg/ml streptomycin, in a humidified atmosphere of 5% CO2 at 37˚C. AG-1478 was dissolved in DMSO for preparation of 10mM stock. For the experiments, the tyrphostin was diluted with RPMI-1640 containing 10% FBS. MDA-MB-231 and MCF-7 cells were treated with serial concentrations of Tyrphostin AG-1478 (5-40μM) for 72h. DMSO (0.1%) was used as a control. The antiproliferative effect was evaluated by MTT assay. ApoDETECT™ Annexin V-FITC Kit and flow cytometry were used for apoptosis assessment. |
Reaction Conditions | 5-40μM; 72h |
Applications | AG-1478 suppressed cellular growth by inhibiting cell proliferation, inducing apoptosis. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice and Male ApoE−/− mice |
Preparation Method | Male C57BL/6 mice and Male ApoE−/− mice weighing 18–20g aged 8 weeks were housed at a constant room temperature with a 12:12h light-dark cycle and fed with a standard rodent diet and water. After an acclimatization period of one week, 28 C57BL/6 or ApoE−/− mice were randomly divided into four weight-matched groups. 7 mice were fed with standard animal low-fat diet containing 10kcal.% fat, 20kcal.% protein and 70kcal.% carbohydrate served as a normal control group (Control or ApoE-LF), while the remaining 21 mice were fed with high-fat diet containing 60kcal.% fat, 20kcal.% protein and 20kcal.% carbohydrate for 16 weeks(HFD). Since 9th week, AG-1478 was given daily by oral gavage at a dose of 10mg/kg/day for the next 8 weeks. Mice in the Control and HFD groups were gavaged with vehicle (1% CMC-Na solution) only. At the day before the sacrifice of ApoE−/− mice, doppler analysis was performed to determine the pathologic cardiac hypertrophy. Mice was anesthetized with isoflurane, echocardiography was performed by SONOS 5500 ultrasound with a 15-MHz linear array ultrasound transducer. At the end of experimental period, all the animals were sacrificed by cervical decapitation. The body weight was recorded. Blood samples were collected and centrifuged at 4°C at 3000rpm for 10min for collecting the serum. The heart was excised aseptically, blotted dry and the weight was recorded followed by immediate freezing in liquid nitrogen and then stored at −80°C before further analyses. |
Dosage form | 10mg/kg/day ; p.o.; 8 weeks |
Applications | AG-1478 significantly blocked high-fat diet-induced cardiac EGFR phosphorylation, and reduced myocardial inflammation, fibrosis, apoptosis, and dysfunction without affecting plasma LDL and TG levels. |
References: | |
| Cas No. | 153436-53-4 | SDF | |
| 别名 | Tyrphostin AG-1478; AG 1478; NSC 693255; AG1478 | ||
| 化学名 | N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine | ||
| Canonical SMILES | COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)Cl)OC | ||
| 分子式 | C16H14ClN3O2 | 分子量 | 315.75 |
| 溶解度 | ≥ 15.8mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1671 mL | 15.8353 mL | 31.6706 mL |
| 5 mM | 0.6334 mL | 3.1671 mL | 6.3341 mL |
| 10 mM | 0.3167 mL | 1.5835 mL | 3.1671 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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- Purity: >99.00%
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