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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2022-03-07 02:51:38 UTC
HMDB IDHMDB0014462
Secondary Accession Numbers
  • HMDB14462
Metabolite Identification
Common NameGefitinib
DescriptionGefitinib, also known as iressa or ZD 1839, belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups. This leads to inappropriate activation of the anti-apoptotic Ras signalling cascade, eventually leading to uncontrolled cell proliferation. Gefitinib is a drug which is used 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. Adverse drug reactions (ADRs) are acceptable for a potentially fatal disease. Gefitinib is a very strong basic compound (based on its pKa). In humans, gefitinib is involved in gefitinib action pathway. IPASS (IRESSA Pan-Asia Study) was a randomized, large-scale, double-blinded study which compared gefitinib vs. carboplatin/ paclitaxel as a first-line treatment in advanced NSCLC.IPASS studied 1,217 patients with confirmed adenocarcinoma histology who were former or never smokers.
Structure
Data?1582753182
Synonyms
ValueSource
4-(3'-Chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazolineChEBI
GefitinibumChEBI
IressaChEBI
IrressatChEBI
N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamineChEBI
ZD 1839ChEBI
ZD-1839ChEBI
ZD1839ChEBI
N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamideHMDB
Chemical FormulaC22H24ClFN4O3
Average Molecular Weight446.902
Monoisotopic Molecular Weight446.152096566
IUPAC NameN-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine
Traditional Namegefitinib
CAS Registry Number184475-35-2
SMILES
COC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C1
InChI Identifier
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)
InChI KeyXGALLCVXEZPNRQ-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazanaphthalenes
Sub ClassBenzodiazines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Anisole
  • Aniline or substituted anilines
  • Alkyl aryl ether
  • Aminopyrimidine
  • Chlorobenzene
  • Fluorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Morpholine
  • Oxazinane
  • Pyrimidine
  • Benzenoid
  • Imidolactam
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary amine
  • Azacycle
  • Dialkyl ether
  • Ether
  • Oxacycle
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic nitrogen compound
  • Amine
  • Organic oxygen compound
  • Organofluoride
  • Organochloride
  • Organopnictogen compound
  • Organohalogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
Process
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.027 g/LNot Available
LogP3.2Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.027 g/LALOGPS
logP4.02ALOGPS
logP3.75ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)16.11ChemAxon
pKa (Strongest Basic)6.85ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area68.74 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity117.51 m³·mol⁻¹ChemAxon
Polarizability46.11 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+203.54930932474
DeepCCS[M-H]-201.19130932474
DeepCCS[M-2H]-235.18330932474
DeepCCS[M+Na]+210.93230932474
AllCCS[M+H]+202.932859911
AllCCS[M+H-H2O]+200.732859911
AllCCS[M+NH4]+205.032859911
AllCCS[M+Na]+205.632859911
AllCCS[M-H]-198.832859911
AllCCS[M+Na-2H]-198.832859911
AllCCS[M+HCOO]-198.932859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
GefitinibCOC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C14951.1Standard polar33892256
GefitinibCOC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C13340.0Standard non polar33892256
GefitinibCOC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C13909.0Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Gefitinib,1TMS,isomer #1COC1=CC2=NC=NC(N(C3=CC=C(F)C(Cl)=C3)[Si](C)(C)C)=C2C=C1OCCCN1CCOCC13453.5Semi standard non polar33892256
Gefitinib,1TMS,isomer #1COC1=CC2=NC=NC(N(C3=CC=C(F)C(Cl)=C3)[Si](C)(C)C)=C2C=C1OCCCN1CCOCC13391.4Standard non polar33892256
Gefitinib,1TMS,isomer #1COC1=CC2=NC=NC(N(C3=CC=C(F)C(Cl)=C3)[Si](C)(C)C)=C2C=C1OCCCN1CCOCC14893.7Standard polar33892256
Gefitinib,1TBDMS,isomer #1COC1=CC2=NC=NC(N(C3=CC=C(F)C(Cl)=C3)[Si](C)(C)C(C)(C)C)=C2C=C1OCCCN1CCOCC13644.1Semi standard non polar33892256
Gefitinib,1TBDMS,isomer #1COC1=CC2=NC=NC(N(C3=CC=C(F)C(Cl)=C3)[Si](C)(C)C(C)(C)C)=C2C=C1OCCCN1CCOCC13566.6Standard non polar33892256
Gefitinib,1TBDMS,isomer #1COC1=CC2=NC=NC(N(C3=CC=C(F)C(Cl)=C3)[Si](C)(C)C(C)(C)C)=C2C=C1OCCCN1CCOCC14869.5Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Gefitinib GC-MS (Non-derivatized) - 70eV, Positivesplash10-0uxr-9424700000-182dba69c82bee61cbe22017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Gefitinib GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Gefitinib LC-ESI-qTof , Positive-QTOFsplash10-0002-1511900000-d0570bedf596999895752017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gefitinib , positive-QTOFsplash10-00di-0193000000-38bb088cc8af6a0e12a42017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gefitinib , positive-QTOFsplash10-0002-1511900000-d0570bedf596999895752017-09-14HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 10V, Positive-QTOFsplash10-0002-0201900000-dafa6866c6b59a71a89e2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 20V, Positive-QTOFsplash10-0udi-2904200000-011d82a75223a5017b872016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 40V, Positive-QTOFsplash10-009l-9402000000-d87048e0478c6d231bfe2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 10V, Negative-QTOFsplash10-0002-0004900000-bb4c9a2e360df1c7e52e2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 20V, Negative-QTOFsplash10-014s-3019400000-c4f741a0f46f6e8edd9f2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 40V, Negative-QTOFsplash10-0uy0-3279000000-593bcb0bda5ac30686172016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 10V, Negative-QTOFsplash10-0002-0000900000-f5b40d44879371ef81fb2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 20V, Negative-QTOFsplash10-0f6t-0005900000-a102859e7a71e3a4e8832021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 40V, Negative-QTOFsplash10-0udi-1029000000-4b9f808b7f687fe38a432021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 10V, Positive-QTOFsplash10-0002-0000900000-fc203d826511c11b8cd12021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 20V, Positive-QTOFsplash10-0fba-1901400000-c8c0d48bbd64a7e7fa9a2021-09-22Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Gefitinib 40V, Positive-QTOFsplash10-0uk9-9515200000-6abbaa993868c8b744f42021-09-22Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00317 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00317 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00317
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID110217
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkGefitinib
METLIN IDNot Available
PubChem Compound123631
PDB IDNot Available
ChEBI ID49668
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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:15284455 ]
  2. 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:15329413 ]
  3. (). FDA label . .

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in transmembrane receptor protein tyrosine kinase activity
Specific function:
Isoform 2 may act as an antagonist of EGF action
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular weight:
134276.2
References
  1. Ciardiello F, Caputo R, Bianco R, Damiano V, Pomatico G, De Placido S, Bianco AR, Tortora G: Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res. 2000 May;6(5):2053-63. [PubMed:10815932 ]
  2. Albanell J, Codony-Servat J, Rojo F, Del Campo JM, Sauleda S, Anido J, Raspall G, Giralt J, Rosello J, Nicholson RI, Mendelsohn J, Baselga J: Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Res. 2001 Sep 1;61(17):6500-10. [PubMed:11522647 ]
  3. Nicholson RI, Hutcheson IR, Harper ME, Knowlden JM, Barrow D, McClelland RA, Jones HE, Wakeling AE, Gee JM: Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer. Endocr Relat Cancer. 2001 Sep;8(3):175-82. [PubMed:11566608 ]
  4. Moasser MM, Basso A, Averbuch SD, Rosen N: The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. 2001 Oct 1;61(19):7184-8. [PubMed:11585753 ]
  5. Arteaga CL, Johnson DH: Tyrosine kinase inhibitors-ZD1839 (Iressa). Curr Opin Oncol. 2001 Nov;13(6):491-8. [PubMed:11673690 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC, Waters CM, Elmeliegy MA, Stewart CF: Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res. 2009 Jul 15;69(14):5885-92. doi: 10.1158/0008-5472.CAN-09-0700. Epub 2009 Jun 30. [PubMed:19567673 ]
General function:
Involved in ATP binding
Specific function:
Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular weight:
72313.5
References
  1. Ozvegy-Laczka C, Hegedus T, Varady G, Ujhelly O, Schuetz JD, Varadi A, Keri G, Orfi L, Nemet K, Sarkadi B: High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol. 2004 Jun;65(6):1485-95. [PubMed:15155841 ]
  2. An Y, Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1529-42. doi: 10.1517/17425250903228834. [PubMed:19708828 ]
  3. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC, Waters CM, Elmeliegy MA, Stewart CF: Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res. 2009 Jul 15;69(14):5885-92. doi: 10.1158/0008-5472.CAN-09-0700. Epub 2009 Jun 30. [PubMed:19567673 ]
  4. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [PubMed:19493273 ]
  5. Shi Z, Parmar S, Peng XX, Shen T, Robey RW, Bates SE, Fu LW, Shao Y, Chen YM, Zang F, Chen ZS: The epidermal growth factor tyrosine kinase inhibitor AG1478 and erlotinib reverse ABCG2-mediated drug resistance. Oncol Rep. 2009 Feb;21(2):483-9. [PubMed:19148526 ]