Gefitinib

• Catalog No.: DB00317
• CAS Number: 184475-35-2
• M. F.: C22H24ClFN4O3
• M. W.: 446.9023632

SYNONYMS

• IUPAC name: N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine
• IUPAC Traditional name: gefitinib
• Brand Name: Irressat; Tarceva; Iressa
• Synonyms: ZD-1839; ZD1839

DATABASE IDS

• PubChem CID: 123631
• PubChem SID: 46508649
• CAS Number: 184475-35-2

PROPERTIES

• Hydrophobicity(logP): 3.2
• Solubility: Sparingly soluble (

DETAILS

Description (English)

• Drug Groups: approved; investigational
• Description: Gefitinib (originally coded ZD1839) is a drug used in the treatment of certain types of cancer. Acting in a similar manner to erlotinib (marketed as Tarceva), gefitinib selectively targets the mutant proteins in malignant cells. It is marketed by AstraZeneca under the trade name Iressa. [Wikipedia]
• Indication: For the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.
• Pharmacology: Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.
• Toxicity: The acute toxicity of gefitinib up to 500 mg in clinical studies has been low. In non-clinical studies, a single dose of 12,000 mg/m^2 (about 80 times the recommended clinical dose on a mg/m^2 basis) was lethal to rats. Half this dose caused no mortality in mice. Symptoms of overdose include diarrhea and skin rash.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic via CYP3A4. Three sites of biotransformation have been identified: metabolism of the N-propoxymorpholino-group, demethylation of the methoxy-substituent on the quinazoline, and oxidative defluorination of the halogenated phenyl group.
• Absorption: Absorbed slowly after oral administration with mean bioavailability of 60%.
• Half Life: 48 hours
• Protein Binding: 90% primarily to serum albumin and alpha 1-acid glycoproteins.
• Elimination: Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.
• Distribution: * 1400 L
• Clearance: * 595 mL/min
• References: Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H: EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11. Epub 2004 Aug 25. [Pubmed] ; Sordella R, Bell DW, Haber DA, Settleman J: Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004 Aug 20;305(5687):1163-7. Epub 2004 Jul 29. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Sordella R, Bell DW, Haber DA, Settleman J: Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004 Aug 20;305(5687):1163-7. Epub 2004 Jul 29. Pubmed
• Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H: EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11. Epub 2004 Aug 25. Pubmed