Studies leading to the identification of ZD1839 (IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer.
This paper describes the development of the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 from a lead series of 4-anilinoquinazoline compounds. ZD1839 has suitable properties for use as a clinically effective drug and shows activity against human tumours. In particular, the use of pharmacokinetic data in the development of ZD1839 is discussed.
Barker
A J
AJ
AstraZeneca, Cancer and Infection Research, Mereside, Alderley Park, Macclesfield, SK10 4TG, Cheshire, UK.
Gibson
K H
KH
Grundy
W
W
Godfrey
A A
AA
Barlow
J J
JJ
Healy
M P
MP
Woodburn
J R
JR
Ashton
S E
SE
Curry
B J
BJ
Scarlett
L
L
Henthorn
L
L
Richards
L
L
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D006801:Humans; D007624:KB Cells / Q000166:cytology; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib