Tyrphostin AG879是一种酪氨酸激酶抑制剂，抑制TrKA的磷酸化，但不抑制TrKB和TrKC。Tyrphostin AG879也是ErbB2激酶抑制剂，对ErbB2的选择性比EGFR高至少500倍(IC50 > 500 μmol/L)。tyrphostinAG879对ErbB2的IC50为1 μmol/L [1]。

体外:AG 879已被广泛用作对ErbB2和FLK-1(一种VEGF受体)特异的Tyr激酶抑制剂。ErbB2和FLK-1的IC50值约为1 μM。在细胞培养中，10 nM的AG 879阻断了Tyr激酶ETK和PAK1(一种CDC42/Rac依赖性Ser/Thr激酶)之间的特异性相互作用。AG 879 (10 nM)在体外直接显示对纯化的ETK和PAK1没有抑制作用，表明该药物通过靶向ETK上游高度敏感的激酶阻断了ETK-PAK1途径。Src对AG 879不敏感。FAK被100纳米AG879抑制，但不被10纳米AG 879抑制[2]。AG 879通过抑制MAP激酶活化来抑制人乳腺癌细胞的增殖。AG 879显著抑制RAF-1基因的表达，该基因编码上游MAPKKK。此外，AG 879抑制HER-2的表达[3]。AG879 (20微米)治疗显著降低了人平滑肌肉瘤(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)细胞系的增殖，同时增加了细胞凋亡[4]。

体内:在移植了HTB-114或HL-60的无胸腺NOD/SCID小鼠中，施用2 mg的AG879诱导了癌症生长的减少[4]。AG 879给药(20 mg/kg)使50%的小鼠完全脱离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显著减小了生长中的肉瘤的大小[5]。

产品性质：

Cas No.:148741-30-4

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

注意事项：

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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.