Gefitinib

Molecular formula C22H24CIFN4O3 Molecular weight 446.90 CAS Registry No 184475-35-2 

Sample preparation Vortex 500 [xL plasma, 25 pL of 1 pg/mL IS in MeOH, 500 pL 1 M NaOH, and 6 mL MTBE for 2 min, centrifuge for 30 s. Remove 5.5 mL of the organic layer and evaporate it to dryness under a stream of nitrogen at 20°, reconstitute the residue with 250 pL mobile phase, inject a 15-100 pL aliquot. 

Stafford, L.E. Swaisland, H.C. Payne, R. A sensitive assay for ZD1839 (Iressa) in human plasma by liquid-liquid extraction and high performance liquid chromatography with mass spec-trometric detection vahdation and use in Phase I clinical trials, J.Pharm.BiomedAnal., 2002, 29, 221-228. 

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Gefitinib (Iressa ) Astra-Zeneca TKI EGFR Metastatic non-small cell lung carcinoma... 

Gefitinib (Iressa) TKI EGFR Inhibition of kinase activity - ATP-competitive NSCLC... 

Rojo F, Tabernero J, Albanell J, et al. Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma. J. Clin. Oncol. 2006 24 4309-4316. 

The unbound fraction of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib has been extensively studied in cancer patients [39]. The drug was found to bind to serum albumin, oq-acid glycoprotein, and red blood cells with a mean unbound fraction of 3.4% which was constant over 28 days of dosing. Unbound fraction ranged from 2.2% to 5.4% and was inversely correlated with pre-treatment levels of oq-acid glycoprotein. 

Figure 12.1 The in silico prediction of the site of metabolism for Gefitinib and Fipronil, and the in silico prediction of MBI for 4-ipomelanol, showing the problematic molecular moiety.

Gefitinib (Iressa) EGFR tyrosine kinase inhibitor Third-line tumor — non-small ceU Irmg Phase II... 

Kris, M.G. et al.. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer a randomized trial, JAMA, 290, 2149-2158, 2003. 

Cohen, M.H. et al., FDA drug approval summary gefitinib (ZD1839) (Iressa) tablets. 

Giaccone, G. et al., Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer a phase 111 trial-lNTACT, /. Clin. Oncol., 22, 777-784, 2004. 

Lynch, T.J. et al.. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to Gefitinib, N. Engl.. Med., 350(21), 2129-2139, 2004. 

Paez, J. et al., EGFR mutations in lung cancer correlation with clinical response to Gefitinib... 

Anticancer drugs Daunorubicin Topotecan 9-Aminocamptothecin SN-38 (iiinotecan metabolite) Epirubicin Mitoxantrone Methotrexate Imatinib Gefitinib (i)... 

Nakamura, Y., Oka, M., Soda, H., et al. (2005) Gefitinib ( Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, reverses breast cancer resistance protein/ ABCG2-mediated drug resistance. Cancer Res. 65, 1541-1546. 

Fukuoka, M., Yano, S., Giaccone, G., et al. (2003) Multi-institutional randomized phase 11 trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial). J Clin Oncol. 21, 2237-2246. 

Cohen, M. H., Williams, G. A., Sridhara, R., et al. (2004) United States Food and Drug Administration drug approval summary gefitinib (ZD1839 Iressa) tablets. Clin Cancer Res. 10, 1212-1218. 

Paez, J. G., Janne, P. A., Lee, J. C., et al. (2004) EGFR mutations in lung cancer correlation with clinical response to gefitinib therapy. Science. 304, 1497-1500. 

Pao, W., Miller, V. A., PoUti, K. A., et al. (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2, e73. 

Two of the small molecule inhibitors, gefitinib (166, EGF receptor kinase inhibitor) and imat-inib (167, Bcr-Abl receptor kinase inhibitor), have reached the market. Although many of the starting leads for kinase inhibitors were obtained by random screening approaches, further medicinal chemistry was aided by the availability of a number of crystal structures and other modelling approaches The design of irreversible... 

Gefitinib 2002 Non-small cell lung cancer EGFR kinase inhibitor [49]... 

Tumour profiling during gefitinib clinical trials has also shown a longer median survival time in patients with a high EGF receptor gene copy num-... 

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