Description
Protein tyrosine kinase (PTK) inhibitors are potential antiproliferative agents for diseases caused by the hyperactivity of PTKs. Tyrphostins are a class of antiproliferative, compounds that act as PTK blockers. PTK inhibitors that preferentially inhibit the epidermal growth factor (EGF) receptor kinase block EGF-dependent cell proliferation. AG-494 is an inhibitor of epidermal growth factor receptor kinase with an IC50 value of 1 μM in HT-22 cells.
Uses
AG-494 is a member of the tyrphostin family of tyrosine kinase inhibitors and is a potent inhibitor of EGF receptor autophosphorylation (IC50=1.2 μM) and EGF-dependent cell growth (IC50=6 μM). It selectively inhibits HER1 (EGF receptor) vs. HER1-2 receptor autophosphorylation (HER1: IC50=1.1 μM; HER1-2: IC50=45 μM). HER1-2 is a chimeric receptor consisting of the external HER1 domain fused to an internal HER2 domain. Blocks CDK2 activation and causescells to arrest at late G1 and during S phase.
Biological Activity
Potent inhibitor of epidermal growth factor receptor (EGFR) kinase (IC 50 = 0.7 μ M). Selective over ErbB2, PDGFR and insulin receptor kinase (IC 50 values are 42, 6 and > 100 μ M respectively).
References
[1]. osherov n, levitzki a. tyrphostin ag 494 blocks cdk2 activation. febs lett, 1997, 410(2-3): 187-190.
[2]. kleinberger-doron n, shelah n, capone r, et al. inhibition of cdk2 activation by selected tyrphostins causes cell cycle arrest at late g1 and s phase. exp cell res, 1998, 241(2): 340-351.
[3]. liu x, qin j, luo q, 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.
[4]. bojko a1, reichert k, adamczyk a, et al. the effect of tyrphostins ag494 and ag1478 on the autocrine growth regulation of a549 and du145 cells. folia histochem cytobiol, 2012, 50(2): 186-195.
