Tyrphostin AG 879 (AG 879) effectively inhibits HER2/ErbB2 (IC50: 1 μM), 100- and 500-fold higher selective to ErbB2 than EGFR and PDGFR.

HER2/ErbB2:1 μM

AG879以浓度依赖的方式抑制FET6αS26X细胞的生长。[1] AG879(10 nM)阻断PAK1的激活，并抑制RAS诱导的NIH 3T3细胞的恶性转化。AG879(<1 μM)抑制v-Ha-RAS转化的NIH 3T3成纤维细胞中ERK的Tyr磷酸化及其与PAK1的结合。[2] AG 879剂量依赖性地减少MCF-7细胞数量，并在0.4 mM时通过抑制DNA合成和有丝分裂显著效果。AG 879(<20 μM)抑制MCF-7细胞中ERK-1/2的激活。AG 879(5 μM)降低Hsp90客户蛋白RAF-1和HER-2的表达。[3] AG879(20 μM)显著减少人类平滑肌肉瘤(HTB-114, HTB-115, HTB-88)、横纹肌肉瘤(HTB-82, TE-671)、前列腺腺癌(PC-3)、急性早幼粒细胞性白血病(HL-60)和组织细胞淋巴瘤(U-937)细胞系的增殖，并伴有凋亡的变化增加。[4]

AG879（2 mg）在接种了HTB-114或HL-60的无胸腺NOD/SCID小鼠中引起癌症生长的减少。[4] AG 879（20 mg/kg）治疗使得50%的小鼠完全没有RAS诱导的肉瘤，并且显著减小了携带v-Ha-RAS转化NIH 3T3细胞的裸鼠中生长肉瘤的大小。[5]

AZD3759 is tested at a single 1 μM concentration across each of 124 kinases from Millipore kinase panel at an ATP concentration that is within 15 μM of their corresponding apparent Km values. In brief, recombinant kinases are incubated within an appropriate buffer containing peptide substrate and radiolabelled γ-33P-ATP together with presence or absence of required inhibitor concentration. The reaction is initiated by adding ATP/Mg2+ mix. After incubation for 40 minutes at room temperature, the reaction is stopped by adding 3% phosphoric acid solution. A portion of reaction mix is spotted onto P30 filter mat to trap peptide and washed three times for 5 minutes with phosphoric acid to remove non-specific γ-33P-ATP. The phosphorylated substrate is then measured by scintillation counting, which determined the level of kinase activity inhibition compared to control reactions[1].

Cells are grown in 96-well plates containing 100 μL medium per well. Ten microliters of MTT solution (5 mg/ml in PBS) is added to each well and incubation continued for 4 h at 37 °C. Subsequently, 100 μL 10% SDS in 0.01 M HCl is added. After incubation at 37°C overnight, absorption is measured at 550 nm in an ELISA reader using a reference filter of 690 nm.(Only for Reference)