Tyrphostin AG879是一種酪氨酸激酶抑制劑，抑制TrKA的磷酸化，但不抑制TrKB和TrKC。Tyrphostin AG879也是ErbB2激酶抑制劑，對(duì)ErbB2的選擇性比EGFR高至少500倍(IC50 > 500 μmol/L)。tyrphostinAG879對(duì)ErbB2的IC50為1 μmol/L [1]。

體外:AG 879已被廣泛用作對(duì)ErbB2和FLK-1(一種VEGF受體)特異的Tyr激酶抑制劑。ErbB2和FLK-1的IC50值約為1 μM。在細(xì)胞培養(yǎng)中，10 nM的AG 879阻斷了Tyr激酶ETK和PAK1(一種CDC42/Rac依賴性Ser/Thr激酶)之間的特異性相互作用。AG 879 (10 nM)在體外直接顯示對(duì)純化的ETK和PAK1沒有抑制作用，表明該藥物通過靶向ETK上游高度敏感的激酶阻斷了ETK-PAK1途徑。Src對(duì)AG 879不敏感。FAK被100納米AG879抑制，但不被10納米AG 879抑制[2]。AG 879通過抑制MAP激酶活化來抑制人乳腺癌細(xì)胞的增殖。AG 879顯著抑制RAF-1基因的表達(dá)，該基因編碼上游MAPKKK。此外，AG 879抑制HER-2的表達(dá)[3]。AG879 (20微米)治療顯著降低了人平滑肌肉瘤(HTB-114、HTB-115、HTB-88)、橫紋肌肉瘤(HTB-82、TE-671)、前列腺腺癌(PC-3)、急性早幼粒細(xì)胞白血病(HL-60)和組織細(xì)胞淋巴瘤(U-937)細(xì)胞系的增殖，同時(shí)增加了細(xì)胞凋亡[4]。

體內(nèi):在移植了HTB-114或HL-60的無胸腺NOD/SCID小鼠中，施用2 mg的AG879誘導(dǎo)了癌癥生長的減少[4]。AG 879給藥(20 mg/kg)使50%的小鼠完全脫離RAS誘導(dǎo)的肉瘤。在攜帶v-Ha-RAS轉(zhuǎn)化的NIH 3T3細(xì)胞的裸鼠中，AG 879顯著減小了生長中的肉瘤的大小[5]。

產(chǎn)品性質(zhì)：

Cas No.:148741-30-4

別名:AG 879

化學(xué)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

儲(chǔ)存條件:Store at -20°C

注意事項(xiàng)：

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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.