In vitro
Tyrphostin AG 1478 is a potent EGFR inhibitor which was noticed in 1996. Tyrphostin AG 1478 can inhibit EGFR with IC50 of 3 nM. AG1478 also strongly inhibited the holoenzyme activity of recombinant human protein kinase CK2 with IC50 of 25.9 umol/L. Tyrphostin AG 1478 did not show too much inhibition to other receptors, for example, tyrphostin AG 1478 inhibit p210(BCR-ABL) with IC50 more than 50 uM while the IC50 of tyrphostin AG 1478 for closely-related HER2(neu/erbB2) receptor and platelet-derived growth factor receptor (PDGFR) are more than 100 uM. AG 1478 can inhibit cell growth, DNA synthesis, EGFR tyrosine kinase activity, and receptor autophosphorylation in UM87MG. And the inhibition behaviors are dose-dependent manners.AG-1478 rapidly and reversibly inhibited Kv1.5 currents at 50 mV in a concentration-dependent manner with an IC50 of 9.82 uM. Besides above, AG1478 influence the proteins which are related to apoptosis. AG1478 up-regulates the expression of the pro-apoptotic member of the BCL-2 family BIM and down-regulates the expression of the anti-apoptotic BCL-XL and MCL1 in Hepatocellular carcinoma (HCC). AG1478 also decreases the levels of the caspase inhibitors HIAP2 and XIAP. AG1478 in different liver tumor cell lines promotes both inhibition of cell proliferation and induction of cell death, which are coincident with arrest in the G1 phase of the cell cycle, caspase-3 activation and DNA fragmentation. As a EGFR inhibitor, AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells by inducing cell cycle arrest in G1 phase and upregulating the levels of protein p27 significantly.
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