Tyrphostin AG 879
(Synonyms: AG 879) 目录号 : GC15271
A non-specific tyrphostin ErbB2 inhibitor
Cas No.:148741-30-4
Sample solution is provided at 25 µL, 10mM.
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Tyrphostin AG879 is a tyrosine kinase inhibitor that inhibits the phosphorylation of TrKA, but not TrKB and TrKC. Tyrphostin AG879 is also a ErbB2 kinase inhibitor, has at least 500-fold higher selectivity to ErbB2 than EGFR (IC50 > 500 μmol/L). The IC50 of tyrphostinAG879 against ErbB2 is 1 μmol/L [1].
In vitro: AG 879 has been widely used as a Tyr kinase inhibitor specific for ErbB2 and FLK-1, a VEGF receptor. The IC50 value for ErbB2 and FLK-1 was approximately 1 μM. AG 879 at 10 nM blocked the specific interaction between the Tyr-kinase ETK and PAK1 (a CDC42/Rac-dependent Ser/Thr kinase) in cell culture. AG 879 (10 nM) showed no inhibitory effects on the purified ETK and PAK1 directly in vitro, suggesting that this drug blocked the ETK-PAK1 pathway by targeting the highly sensitive kinase upstream of ETK. Src was insensitive to AG 879. FAK was inhibited by 100 nM AG 879, but not by 10 nM AG879 [2]. AG 879 inhibited proliferation of human breast cancer cells through an effect involving inhibition of MAP kinase activation. AG 879 markedly inhibited the expression of the RAF-1 gene, which encoded an upstream MAPKKK. Additionally, AG 879 inhibited the expression of HER-2[3]. Treatment with AG879 (20 μM) dramatically decreased proliferation with a variable increase in apoptosis in Cell lines from human leiomyosarcoma (HTB-114, HTB-115, HTB-88), rhabdomyosarcoma (HTB-82, TE-671), prostatic adenocarcinoma (PC-3), acute promyelocytic leukemia (HL-60) and histiocytic lymphoma (U-937) [4].
In vivo: In athymic NOD/SCID mice grafted with HTB-114 or HL-60, administration of AG879 at 2 mg induced a decrease in cancer growth [4]. AG 879 administration (20 mg/kg) kept 50% of mice absolutely free of RAS-induced sarcomas. In the nude mice carrying v-Ha-RAS transformed NIH 3T3 cells, AG 879 dramatically reduced the size of the growing sarcomas [5].
References:
[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.
| Cell experiment [1,2]: | |
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Cell lines |
MCF-7 cells, MDA-MB-231 cells, SK-BR-3 cells, human leiomyosarcoma (HTB-114, HTB-115, HTB-88), rhabdomyosarcoma (HTB-82, TE-671), prostatic adenocarcinoma (PC-3), acute promyelocytic leukemia (HL-60) and histiocytic lymphoma (U-937) |
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Preparation method |
Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
20 μM, 24 h |
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Applications |
In MCF-7 cells, AG 879 dose-dependently reduced cell numbers and showed a significant effect at 0.4 μM. AG 879 showed a potent effect on MDA-MB-231 cells and SK-BR-3 cells. Treatment with AG 879 for 24 h inhibited activation of ERK-1/2. AG 879 markedly reduced cell numbers and mitotic figures. AG 879 (5 μM) significantly reduced levels of RAF-1 mRNA after 6 and 24 h treatment. AG 879 (5 μM) significantly reduced levels of HER-2 mRNA. AG 879 (20 μM) decreased HER-2 mRNA levels in overexpressing SK-BR-3 cells. Treatment with AG879 (20 μM) dramatically decreased proliferation with a variable increase in apoptosis in cell lines from human leiomyosarcoma (HTB-114, HTB-115, HTB-88), rhabdomyosarcoma (HTB-82, TE-671), prostatic adenocarcinoma (PC-3), acute promyelocytic leukemia (HL-60) and histiocytic lymphoma (U-937). |
| Animal experiment [2,3]: | |
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Animal models |
Athymic NOD/SCID mice grafted with HTB-114 or HL-60, Nude mice carrying v-Ha-RAS transformed NIH 3T3 cells |
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Dosage form |
Subcutaneous injection |
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Application |
Treatment with AG879 (2 mg) in immunodepressed mice grafted with leiomyosarcoma or promyelocytic leukemia cells (HTB-114 or HL-60) resulted in dramatic reductions in tumor sizes. AG 879(20 mg/kg) treatment kept 50% of mice absolutely free of RAS-induced sarcomas, and dramatically reduced the size of the growing sarcomas in the nude mice carrying v-Ha-RAS transformed NIH 3T3 cells. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 148741-30-4 | SDF | |
| 别名 | AG 879 | ||
| 化学名 | (E)-3-amino-2-[(3,5-ditert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-3-sulfanylprop-2-enenitrile | ||
| Canonical SMILES | CC(C)(C)C1=CC(=CC(=C(N)S)C#N)C=C(C1=O)C(C)(C)C | ||
| 分子式 | C18H24N2OS | 分子量 | 316.46 |
| 溶解度 | ≥ 31.6mg/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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.16 mL | 15.7998 mL | 31.5996 mL |
| 5 mM | 0.632 mL | 3.16 mL | 6.3199 mL |
| 10 mM | 0.316 mL | 1.58 mL | 3.16 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet