Human epidermal growth factor receptor (EGFR; HER1,erbB1), human epidermal growth factor r eceptor 2 (HER2; erbB2), HER3 (erbB3) and HER4 (erbB4) are members of the ErbB family of transmembrane receptor tyrosine kinases. Among them, HER2 is a validated and high-value target. Approximately 30% of breast cancers have an amplification of the HER2/neu gene or overexpression of its protein product, HER2. Also, overexpression of HER2 occurs in gastric, colorectal, NSCLC and ovarian cancers. Tyrphostin AG 879 is a dual HER2 and Trk inhibitor with IC50 values of 1μM and 10μM, respectively[1]. Treatment with 100μM Tyrphostin AG879 in PC12 cells showed inhibition of Trk-A phosphorylation[2]. Exposure to 20μM Tyrphostin AG 879 for 24h led to decreased phosphorylation of ERK-1 and 2 and decreased protein levels of RAF-1 and HER-2 in MCF-7 cells. Tyrphostin AG 879 at concentration<20μM dose-dependently reduced cell growth of MCF-7, MDA-MB-231 and SK-BR-3 cells[3]. Blocking Trk in vivo by ICV infusions of Tyrphostin AG879 (10μl, 0.5mM in DMSO 10% (V/V) in PBS) impaired both short-term and long-term recognition memory[4].
Tyrphostin AG 879 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human osteosarcoma U2OS cells
50 µg/mL
4 hours
Inhibition of antibody secretion
Cells. 2023 Jun 16;12(12):1642.
Rat ovarian cells
>4 µM
10 days
Inhibition of NTRK3 receptor signaling, resulting in oocyte death and a significant reduction in follicle pool size.
Reproduction. 2009 Oct;138(4):697-707.
HEK293 cells
5 µM
12 and 24 hours
AG879 inhibits ErbB4 kinase activity, reducing the stability of PSD-95 protein
J Neurosci. 2011 Jan 5;31(1):15-25.
A549 cells
10 µM
18 hours
Test the inhibitory effect of AG879 on different influenza virus strains, results showed AG879 significantly reduced virus yield.
J Virol. 2011 Mar;85(6):2818-27.
SK-BR-3 cells
0.4-20 µM
24-46 hours
AG 879 significantly inhibited the proliferation of SK-BR-3 cells by inhibiting the expression of RAF-1 and HER-2, thereby inhibiting the activation of the MAPK signaling pathway.
Cell Mol Life Sci. 2004 Oct;61(19-20):2624-31.
MDA-MB-231 cells
0.4-20 µM
24-46 hours
AG 879 significantly inhibited the proliferation of MDA-MB-231 cells by inhibiting the expression of RAF-1 and HER-2, thereby inhibiting the activation of the MAPK signaling pathway.
Cell Mol Life Sci. 2004 Oct;61(19-20):2624-31.
MCF-7 cells
0.4-20 µM
24-46 hours
AG 879 significantly inhibited the proliferation of MCF-7 cells by inhibiting the expression of RAF-1 and HER-2, thereby inhibiting the activation of the MAPK signaling pathway.
Cell Mol Life Sci. 2004 Oct;61(19-20):2624-31.
Rat cortical neurons
10 µM
30 min
Inhibited Trk receptors, blocking H C-TeTx-induced phosphorylation of Akt, MEK-1/2, ERK-1/2, and p90Rsk
Biochem J. 2003 Jul 15;373(Pt 2):613-20.
Rat sensory neurons
30 µM
30 minutes
To investigate the effect of AG879 on BDNF-induced sensitization of sensory neurons, results showed that pretreatment with AG879 did not affect the sensitizing action of BDNF.
J Physiol. 2008 Jul 1;586(13):3113-27.
GABAergic interneurons
5 µM
4 hours
AG879 inhibits ErbB4 kinase activity, leading to increased PSD-95 protein degradation and reduced number and size of PSD-95 puncta
J Neurosci. 2011 Jan 5;31(1):15-25.
MDCK cells
10 µM
48 hours
Evaluate the effect of AG879 on influenza virus replication, results showed AG879 significantly inhibited viral gene expression and virus yield.
J Virol. 2011 Mar;85(6):2818-27.
CHO-K1 cells
3, 10, 20 µM
5-7 minutes
Investigated the effect of AG879 on Kv4.2/KChIP2 channels, found AG879 significantly accelerated the inactivation rate and showed use-dependent block.
Br J Pharmacol. 2015 Jul;172(13):3370-82.
Hippocampal neurons
20 µM
Studied the effect of AG879 on A-type potassium currents in hippocampal neurons, found AG879 significantly inhibited A-type potassium currents.
Br J Pharmacol. 2015 Jul;172(13):3370-82.
Tyrphostin AG 879 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Neonatal rats
Subcutaneous injection
7.6 mg/kg/day (5-day old rats) and 6.7 mg/kg/day (25-day old rats)
Once daily for 5 days
Inhibition of NTRK3 receptor signaling in vivo, no significant changes in follicle development rates or oocyte death were observed.
Reproduction. 2009 Oct;138(4):697-707.
BALB/c mice
Influenza A/PR8 virus infection model
Intraperitoneal injection
5 mg/kg
Once daily for 5 days
Evaluate the antiviral activity of AG879 in a mouse model of influenza virus infection, results showed significant reduction in viral replication and mortality
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