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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:38 UTC
HMDB IDHMDB14462
Secondary Accession NumbersNone
Metabolite Identification
Common NameGefitinib
DescriptionGefitinib (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]
Structure
Thumb
Synonyms
ValueSource
4-(3'-chloro-4'-fluoroanilino)-7-Methoxy-6-(3-morpholinopropoxy)quinazolineChEBI
IressaChEBI
N-(3-chloro-4-Fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamineChEBI
ZD 1839ChEBI
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 KeyInChIKey=XGALLCVXEZPNRQ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound 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
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Anisole
  • Halobenzene
  • Fluorobenzene
  • Chlorobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Oxazinane
  • Morpholine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Oxacycle
  • Azacycle
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.70e-02 g/LNot Available
LogP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.027 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity117.51 m3·mol-1ChemAxon
Polarizability46.11 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Gefitinib PathwaySMP00473Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00317
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00317
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00317
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID110217
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkGefitinib
NuGOwiki LinkHMDB14462
Metagene LinkHMDB14462
METLIN IDNot Available
PubChem Compound123631
PDB IDIRE
ChEBI ID49668
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. [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. [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. Epub 2009 Nov 24. [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. [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. [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. [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. [11585753 ]
  5. Arteaga CL, Johnson DH: Tyrosine kinase inhibitors-ZD1839 (Iressa). Curr Opin Oncol. 2001 Nov;13(6):491-8. [11673690 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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. Epub 2009 Nov 24. [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. Epub 2009 Jun 30. [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. [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. [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. Epub 2009 Jun 30. [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. Epub 2009 May 12. [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. [19148526 ]