Tyrphostin AG 879
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Tyrphostin AG879是酪氨酸激酶抑制剂,抑制TrKA磷酸化,但对TrKB和TrKC没有作用。Tyrphostin AG879也是一种ErbB2激酶抑制剂,对于ErbB2的IC50 为1 μmol/L,比对EGFR的选择性高至少500倍,针对EGFR的IC50大于 500 μmol/L[1]。
体外实验:AG 879已广泛用作ErbB2和VEGF受体FLK-1的特异性Tyr激酶抑制剂。对ErbB2和FLK-1的IC50值约为1 μM。在细胞培养物中,10 nM的AG 879阻断了Tyr激酶ETK和CDC42/Rac依赖性Ser/Thr激酶PAK1之间的特异性相互作用。10 nM的AG 879在体外对纯化的ETK或PAK1没有产生直接抑制作用,表明该药物通过靶向ETK上游的高敏感性激酶,从而阻断ETK-PAK1途径。Src对AG 879不敏感, 100 nM AG 879抑制FAK,但10 nM AG879不产生抑制作用[2]。AG 879通过抑制MAP激酶的活化进而抑制人乳腺癌细胞的增殖。AG 879显著抑制编码上游MAPKKK的RAF-1基因的表达。此外,AG 879抑制HER-2的表达[3]。在人类平滑肌肉瘤(HTB-114、HTB-115、HTB-88)、横纹肌肉瘤(HTB-82、TE-671)、前列腺腺癌细胞系PC-3、急性早幼粒细胞白血病(HL-60)和组织细胞淋巴瘤(U-937)细胞中,20 μM AG 879显著降低细胞增殖并诱导凋亡[4]。
在体实验:在HTB-114或HL-60移植的无胸腺NOD/SCID小鼠中,2 mg的AG879抑制癌症生长[4]。20 mg/kg AG 879保持50%的小鼠完全没有RAS诱导的肉瘤。在携带v-Ha-RAS转化的NIH 3T3细胞的裸鼠中,AG 879显著减少了生长肉瘤的大小[5]。
参考文献:
[1]. Levitzki A1, Gazit A. Tyrosine kinase inhibition: an approach to drug development. Science. 1995 Mar 24;267(5205):1782-8.
[2]. He H1, Hirokawa Y, Gazit A, Yamashita Y, Mano H, Kawakami Y,Kawakami, Hsieh CY, Kung HJ, Lessene G, Baell J, Levitzki A, Maruta H. The Tyr-kinase inhibitor AG879, that blocks the ETK-PAK1 interaction, suppresses the RAS-induced PAK1 activation and malignant transformation. Cancer Biol Ther. 2004 Jan;3(1):96-101. Epub 2004 Jan 29.
[3]. Larsson LI1. Novel actions of tyrphostin AG 879: inhibition of RAF-1 and HER-2 expression combined with strong antitumoral effects on breast cancer cells. Cell Mol Life Sci. 2004 Oct;61(19-20):2624-31.
[4]. Rende M1, Pistilli A, Stabile AM, Terenzi A, Cattaneo A, Ugolini G, Sanna P.
Role of nerve growth factor and its receptors in non-nervous cancer growth: efficacy of a tyrosine kinase inhibitor (AG879) and neutralizing antibodies antityrosine kinase receptor A and antinerve growth factor: an in-vitro and in-vivo study. Anticancer Drugs. 2006 Sep;17(8):929-41.
[5]. He H1, Hirokawa Y, Manser E, Lim L, Levitzki A, Maruta H. Signal therapy for RAS-induced cancers in combination of AG 879 and PP1, specific inhibitors for ErbB2 and Src family kinases, that block PAK activation. Cancer J. 2001 May-Jun;7(3):191-202.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 316.46 |
Cas No. | 148741-30-4 |
Formula | C18H24N2OS |
Solubility | insoluble in H2O; ≥2.36 mg/mL in EtOH with ultrasonic; ≥31.6 mg/mL in DMSO |
Chemical Name | (E)-3-amino-2-[(3,5-ditert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-3-sulfanylprop-2-enenitrile |
SDF | Download SDF |
Canonical SMILES | CC(C)(C)C1=CC(=CC(=C(N)S)C#N)C=C(C1=O)C(C)(C)C |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1,2]: | |
细胞系 |
MCF-7细胞,MDA-MB-231细胞,SK-BR-3细胞,人平滑肌肉瘤(HTB-114,HTB-115,HTB-88),横纹肌肉瘤(HTB-82,TE-671),前列腺腺癌(PC-3),急性早幼粒细胞白血病(HL-60)和组织细胞淋巴瘤(U-937) |
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
20 μM,24 h |
应用 |
在MCF-7细胞中,AG 879以剂量依赖性方式减少细胞数,0.4 μM作用显著。AG 879对MDA-MB-231细胞和SK-BR-3细胞具有强效作用。用AG 879处理24小时可抑制ERK-1/2的激活。AG 879显著降低细胞数量和有丝分裂。AG 879(5 μM)在治疗6和24小时后显著降低RAF-1 mRNA的水平。AG 879(5 μM)显著降低HER-2 mRNA的水平。在过表达的SK-BR-3细胞中,AG 879(20 μM)降低HER-2 mRNA水平。在人平滑肌肉瘤(HTB-114、HTB-115、HTB-88),横纹肌肉瘤(HTB-82、TE-671)、前列腺腺癌(PC-3)、急性早幼粒细胞白血病(HL-60)和组织细胞淋巴瘤(U-937)中,使用AG879(20 μM)治疗可显著降低细胞增殖,增加细胞凋亡。 |
动物实验 [2,3]: | |
动物模型 |
HTB-114或HL-60接种的无胸腺NOD/SCID小鼠,携带v-Ha-RAS转化的NIH 3T3细胞的裸鼠 |
给药剂量 |
皮下注射 |
应用 |
在平滑肌肉瘤或早幼粒细胞白血病细胞(HTB-114或HL-60)接种的免疫抑制小鼠中,AG879(2 mg)显著降低肿瘤大小。在携带v-Ha-RAS转化的NIH 3T3细胞的裸鼠中,AG 879(20 mg/kg)治疗保持50%的小鼠绝对不含RAS诱导的肉瘤,并显著降低生长肉瘤的体积。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Larsson L I. Novel actions of tyrphostin AG 879: inhibition of RAF-1 and HER-2 expression combined with strong antitumoral effects on breast cancer cells[J]. Cellular and molecular life sciences, 2004, 61(19): 2624-2631. [2]. Rende M, Pistilli A, Stabile A M, et al. Role of nerve growth factor and its receptors in non-nervous cancer growth: efficacy of a tyrosine kinase inhibitor (AG879) and neutralizing antibodies antityrosine kinase receptor A and antinerve growth factor: an in-vitro and in-vivo study[J]. Anti-cancer drugs, 2006, 17(8): 929-941. [3]. He H, Hirokawa Y, Manser E, et al. Signal therapy for RAS-induced cancers in combination of AG 879 and PP1, specific inhibitors for ErbB2 and Src family kinases, that block PAK activation[J]. Cancer journal (Sudbury, Mass.), 2000, 7(3): 191-202. |
质量控制和MSDS
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