4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[3-(4-morpholinyl)propoxy]quinazoline hydrochloride

Biological Activity

the egfr is a mr 170,000 transmembrane glycoprotein with an external binding domain and an intracellular tyrosine kinase domain. gefitinib (zd-1839, iressa) is an epidermal growth factor receptor-selective tyrosine kinase inhibitor.

in vitro

gefitinib inhibited colony formation in soft agar in a dose dependent manner in all cancer cell lines. however, treatment with higher doses resulted in a 2–4-fold increases in apoptosis. dose-dependent supra-additive increase in growth inhibition was observed when cancer cells were treated with totoxic drugs and gefitinib. the combined treatment markedly enhanced apoptotic cell death induced by single agent treatment [1].

in vivo

gefitinib treatment of nude mice bearing established human geo colon cancer xenografts revealed a reversible dose-dependent inhibition of tumor growth because geo tumors resumed the growth rate of controls at the end of the treatment [1].

target

Target	Value
EGFR (Cell-free assay)	15.5 nM
EGFR (858R/T790M) (Cell-free assay)	823.3 nM

References

[1] ciardiello f, caputo r, bianco r, damiano v, pomatico g, de placido s, bianco ar, tortora g. antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by zd-1839 (iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. clin cancer res. 2000;6(5):2053-63.
[2] cantarini mv, mcfarquhar t, smith rp, bailey c, marshall al. relative bioavailability and safety profile of gefitinib administered as a tablet or as a dispersion preparation via drink or nasogastric tube: results of a randomized, open-label, three-period crossover study in healthy volunteers. clin ther. 2004;26(10):1630-6.