EGFR epidermal growth factor kinase activation

BaselgaJ, HerbstR, LoRussoP, etal. Continuous administration of ZD 1839 (Iressa), a novel epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in patients with five selected tumor types evidence of activity and good tolerability. ProcAm Soc Clin Oncol 2000 19 177 (abstr). 

Mechanism of Action Ahuman epidermal growth factor that inhibits tyrosine kinases (TK) associated with transmembrane cell surface receptors found on both normal and cancer cells. One such receptor is epidermal growth factor receptor (EGFR). Therapea-tic Effect TK activity appears to be vitally important to cell proliferation and survival. Pharmacokinetics About 60% is absorbed after PO administration bioavailability is increased by food to almost 100%. Protein binding 93%. Extensively metabolized in liver. Primarily eliminated in feces minimal excretion in urine. Half-life 36 hr. 

Wissner A, Overbeek E, Reich MF et al. Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (ElER-2). JMed Chem 2003 46 49-63. 

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