Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0764)
Drug Name
Gefitinib
Synonyms
Gefitinib; Iressa; Irressat; ZD 1839; ZD-1839; ZD1839; gefitinib (zd1839); 184475-35-2; 4-(3'-Chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline; CCRIS 9011; CHEMBL939; N-(3-Chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine; N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine; N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine; UNII-S65743JHBS
Indication Lung cancer [ICD11: 2C25] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 446.9 Topological Polar Surface Area 68.7
Heavy Atom Count 31 Rotatable Bond Count 8
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
123631
PubChem SID
532631 ; 7849039 ; 8035066 ; 10240807 ; 10318995 ; 11377941 ; 12015033 ; 14833109 ; 21317853 ; 24424016 ; 24424024 ; 24424026 ; 29215403 ; 29215404 ; 29303859 ; 46508649 ; 47646567 ; 49635529 ; 49742641 ; 50040863 ; 50100103 ; 53319998 ; 53788589 ; 53799235 ; 56312091 ; 56313236 ; 56313469 ; 57340492 ; 61127928 ; 81092810 ; 85171051 ; 92308715 ; 92717784 ; 93581024 ; 99436946 ; 99444469 ; 103024897 ; 103244983 ; 103905343 ; 103905344 ; 104418951 ; 104829175 ; 117865087 ; 118047033 ; 123105108 ; 124756943 ; 124892204 ; 124892205 ; 124892206 ; 125001914
ChEBI ID
ChEBI:49668
CAS Number
184475-35-2
TTD Drug ID
D09XZB
Formula
C22H24ClFN4O3
Canonical SMILES
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4
InChI
1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27)
InChIKey
XGALLCVXEZPNRQ-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Desmethyl-gefitinib M523595 DM002086
135496227
Oxidation - O-Demethylation 1 [4] , [5]
Metabolism of the N-propoxymorpholino-group DM002085 N. A. Unclear 1 [6]
Oxidative defluorination of the halogenated phenyl group DM002087
11190016
Oxidation - Oxidative Defluorination 1 [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001115 Gefitinib Metabolism of the N-propoxymorpholino-group Unclear CYP1A1 ... [6]
MR001116 Gefitinib Desmethyl-gefitinib M523595 Oxidation - O-Demethylation CYP3A4 [4], [5]
MR001117 Gefitinib Oxidative defluorination of the halogenated phenyl group Oxidation - Oxidative Defluorination CYP1A1 ... [6]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[2]
References
1 Gefitinib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7.
3 Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Clin Pharmacokinet. 2005;44(10):1067-81.
4 Minimal contribution of desmethyl-gefitinib, the major human plasma metabolite of gefitinib, to epidermal growth factor receptor (EGFR)-mediated tumour growth inhibition Xenobiotica. 2006 Jan;36(1):29-39. doi: 10.1080/00498250500523253.
5 An investigation into possible interactions among four vascular epidermal growth factor receptor-tyrosine kinase inhibitors with gefitinib. Cancer Chemother Pharmacol. 2021 Jan;87(1):43-52. doi: 10.1007/s00280-020-04191-0.
6 Reactive metabolite of gefitinib activates inflammasomes: implications for gefitinib-induced idiosyncratic reaction J Toxicol Sci. 2020;45(11):673-680. doi: 10.2131/jts.45.673.

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.