AG-494

Names

[ Name ]:
AG-494

[Synonym ]:
Tyrphostin 48
2-Propenamide, 2-cyano-3-(3,4-dihydroxyphenyl)-N-phenyl-, (2E)-
HMS3266B19
(2E)-2-Cyano-3-(3,4-dihydroxyphenyl)-N-phenylacrylamide
AG-494

Biological Activity

[Description]:

AG-494 (Tyrphostin AG 494) is a potent and selective EGFR tyrosine kinase inhibitor (IC50=0.7 μM). AG-494 inhibits the autophosphorylation of EGFR, ErbB2, HER1-2 and PDGF-R with IC50s 1.1, 39, 45 and 6 μM, respectively. AG-494 blocks Cdk2 activation and inhibits EGF-dependent DNA synthesis[1][2][3].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

[Target]

EGFR:0.7 μM (IC50)

[In Vitro]

In DHER-14 cells, AG 494 inhibits Cdk2 activation and EGF-dependent DNA synthesis[2]. AG-494 significantly prevents NF-kB activation in silica-stimulated cells, and also reduces NF-kB activation in H2O2-treated cells[4]. AG-494 (3-9 μM; 5-7 days) inhibits BMP9-induced ALP activity in a dose-dependent manner[5].

[References]

[1]. Gazit A, et al. Tyrphostins. 2. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases. J Med Chem. 1991;34(6):1896-1907.

[2]. Osherov N, et al. Tyrphostin AG 494 blocks Cdk2 activation. FEBS Lett. 1997;410(2-3):187-190.

[3]. Osherov N, et al. Selective inhibition of the epidermal growth factor and HER2/neu receptors by tyrphostins. J Biol Chem. 1993 May 25;268(15):11134-42.

[4]. Liu X, Qin J, et al. Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells. J Cell Mol Med. 2013;17(9):1160-1172.

[5]. Jihee Lee Kang, et al. SILICA-INDUCED NUCLEAR FACTOR- k B ACTIVATION: INVOLVEMENT OF REACTIVE OXYGEN SPECIES AND PROTEIN TYROSINE KINASE ACTIVATION. Journal of Toxicology and Environmental Health, Part A.