In vitro activity: PD 168393 is docked into the ATP binding pocket of EGFR TK. PD168393 completely suppresses EGF-dependent receptor autophosphorylation in A431 cells during continuous exposure, with continous suppression even after 8 hr in compound-free medium. PD168393 inhibits heregulin-induced tyrosine phosphorylation in MDA-MB-453 cells with IC50 of 5.7 nM. PD168393 is inactive against insulin, PDGF and basic FGFR TKs as well as PKC. PD168393 inhibits EGF-mediated tyrosine phosphorylation in HS-27 human fibroblasts with IC50 of 1-6 nM but has little effect on FGF- or PDGF-mediated tyrosine phosphorylation. PD168393 shows rapid and potent inhibition of Her2-induced tyrosine phosphorylation with IC50 of ~100 nM in 3T3-Her2 cells. D168393 also inhibits phosphorylation of PLCγ1/Stat1/Dok1/δ-catenin in 3T3-Her2 cells, except for Fyb.

Kinase Assay: PD168393 is an potent, cell-permeable, irreversible EGFR inhibitor with IC50 of 0.70 nM, irreversibly alkylate Cys-773, inactive against insulin, PDGFR, FGFR and PKC. target: EGFR IC 50: 0.7 nM (1) PD 168393 inhibite EGFr autophosphorylation in A431 human epidermoid carcinoma cells with>9-fold greater potency than PD 174265. (2) PD 168393 decrease the production of TNF-α and phosphrylation of ERK1/2 and p38 induced by LPS in cardiomyocytes. (3) PD168393 completely inhibits AKT and ERK phosphorylation at concentrations as low as 0.03 umol/L. (4) PD168393 could induce apoptosis and inhibit cell growth in ErbB2 positive lung and breast cancer cell lines. (5) PD168393 disrupted MEK1/p44/42 ERK signaling in HaCaT cells as determined by inhibition of phospho-p44/42 ERK.

Cell Assay: (1) PD 168393 inhibite EGFr autophosphorylation in A431 human epidermoid carcinoma cells with>9-fold greater potency than PD 174265. (2) PD 168393 decrease the production of TNF-α and phosphrylation of ERK1/2 and p38 induced by LPS in cardiomyocytes. (3) PD168393 completely inhibits AKT and ERK phosphorylation at concentrations as low as 0.03 umol/L. (4) PD168393 could induce apoptosis and inhibit cell growth in ErbB2 positive lung and breast cancer cell lines.