AG 555(Tyrphostin B46)

AG 555 is an EGFR tyrosine kinase inhibitor.

Research Areas >> Cancer

EGFR

The tyrosine kinase inhibitor (Tyrphostin) AG 555 selectively interferes with viral transcription in bovine papillomavirus type 1 (BPV-1)-transformed fibroblasts and induces suppression of cyclin-dependent kinase activity and cell cycle arrest. AG 555 treatment also leads to an activation of the mitogen-activated protein kinase pathway by enhancing phosphorylation of JNK and p38. Tyrphostin AG 555 disturbs the balance of negative and positive regulatory factors necessary to maintain the homeostasis of a virus-transformed phenotype. Tyrphostin AG 555 can selectively suppress BPV-1 transcription through MAP kinase pathway activation and binding of phosphorylated Jun/ATF-2 at a novel intragenic regulatory sequence. AG 555 affects the transcription of the major regulatory viral protein E2 by shifting the ratio between E2 transactivator in favor to the repressor function. Cell incubation in the presence of 30 μM AG 555 results in a selective down-regulation of the most abundant viral transcripts already 4 h after drug application[2]. Tyrphostins AG555, which blocks Cdk2 activation, induces growth arrest of immortalized cells at G1-S and early S and is very effective in arresting the growth of EGFR overexpressor cells. AG55 inhibits the growth of HPV16-immortalized cells. AG555 is already effective at 10 μM (IC50=6.4, respectively), and the cells remain arrested after withdrawal of the compound on day 5 as monitored on days 8 and 12[3].

ID13 mouse fibroblasts are maintained in Dulbecco's modified Eagle's medium supplemented with 5% (v/v) fetal calf serum, 100 units/mL Penicillin, and 100 μg/mL Streptomycin. Cells are seeded at 2.5×104 cells/cm2 to ensure logarithmic growth. The final concentration of the Tyrphostin AG 555 is 30 μM in all experiments. Stock solutions of 10 mM in Me2SO are stored at -80°C. To exclude potential Me2SO effects, the same final concentrations (0.3%) of Me2SO are added to nontreated controls. Actinomycin D is dissolved in water and added to cells in a final concentration of 5 μg/mL. SB 203580 is dissolved in Me2SO (stock concentration: 50 mM) and used in a final concentration of 10 μM[2].

[1]. Michaelis M, et al. Cisplatin-resistant neuroblastoma cells express enhanced levels of epidermal growth factor receptor (EGFR) and are sensitive to treatment with EGFR-specific toxins. Clin Cancer Res. 2008 Oct 15;14(20):6531-7.

[2]. Baars S, et al. Tyrphostin AG 555 inhibits bovine papillomavirus transcription by changing the ratio between E2 transactivator/repressor function. J Biol Chem. 2003 Sep 26;278(39):37306-13.

[3]. Ben-Bassat H, et al. Tyrphostins that suppress the growth of human papilloma virus 16-immortalized human keratinocytes. J Pharmacol Exp Ther. 1999 Sep;290(3):1442-57.

Osimertinib (AZD9291) | Tyrphostin B42 (AG-490) | Neratinib (HKI-272) | Genistein | (-)-Epigallocatechin gallate | AG-1478 | Dacomitinib (PF-00299804) | Irbinitinib | Poziotinib | Olmutinib | Sapitinib | AZD-3759 | Pyrotinib | Canertinib dihydrochloride | BMS-690514