Identification

Name
Gefitinib
Accession Number
DB00317
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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 446.902
Monoisotopic: 446.152096566
Chemical Formula
C22H24ClFN4O3
Synonyms
  • 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline
  • Gefitinib
  • N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamine
External IDs
  • ZD 1839
  • ZD-1839
  • ZD1839

Pharmacology

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.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

Mechanism of action

Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to enhanced activation of the anti-apoptotic Ras signal transduction cascades, subsequently resulting in increased survival of cancer cells and uncontrolled cell proliferation. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. By inhibiting EGFR tyrosine kinase, the downstream signaling cascades are also inhibited, resulting in inhibited malignant cell proliferation.

TargetActionsOrganism
AEpidermal growth factor receptor
antagonist
Humans
Absorption

Absorbed slowly after oral administration with a mean bioavailability of 60%. Peak plasma levels occurs 3-7 hours post-administration. Food does not affect the bioavailability of gefitinib.

Volume of distribution
  • 1400 L [IV administration]
Protein binding

90% primarily to serum albumin and alpha 1-acid glycoproteins (independent of drug concentrations).

Metabolism

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.

Route of 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.

Half-life

48 hours [IV administration]

Clearance
  • 595 mL/min [IV administration]
Adverse Effects
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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/m2 (about 80 times the recommended clinical dose on a mg/m2 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
Pathways
PathwayCategory
Gefitinib Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
ATP-binding cassette sub-family G member 2---(A;C)A alleleADR Directly StudiedPatients with this genotype have an increased risk of diarrhea with gefitinib.Details
Epidermal growth factor receptorL858R(G;G) / (G;T)T > GEffect Directly StudiedThe presence of this polymorphism in EGFR is associated with a higher response rate to gefitinib.Details
Epidermal growth factor receptorG719A/C(T;T) / (G;T) / (A;A) / (A;G) / (C;C) / (C;G)G > A or C or TEffect Directly StudiedThe presence of this polymorphism in EGFR is associated with a higher response rate to gefitinib.Details
Epidermal growth factor receptorL861Q(A;A) / (A;T) / (G;G) / (G;T)T > A or GEffect Directly StudiedThe presence of this polymorphism in EGFR is associated with a higher response rate to gefitinib.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Gefitinib.
AbametapirThe serum concentration of Gefitinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Gefitinib can be increased when combined with Abatacept.
AbemaciclibGefitinib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AbirateroneThe metabolism of Gefitinib can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Gefitinib can be decreased when combined with Acalabrutinib.
AcebutololThe metabolism of Gefitinib can be decreased when combined with Acebutolol.
AcenocoumarolGefitinib may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Gefitinib.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Gefitinib.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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  • Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products.
  • Take with or without food. The absorption is unaffected by food.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IressaTablet, film coated250 mgOralAstra Zeneca Ab2009-06-24Not applicableEU flag
IressaTablet250 mgOralAstra Zeneca2003-12-17Not applicableCanada flag
IressaTablet, film coated250 mgOralAstra Zeneca Ab2009-06-24Not applicableEU flag
IressaTablet, coated250 mg/1OralAstraZeneca Pharmaceuticals LP2015-07-13Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-gefitinibTabletOralApotex Corporation2017-10-18Not applicableCanada flag
Jamp GefitinibTabletOralJamp Pharma CorporationNot applicableNot applicableCanada flag
Nat-gefitinibTabletOralNatco Pharma Limited2019-11-13Not applicableCanada flag
Sandoz GefitinibTabletOralSandoz Canada Incorporated2019-06-26Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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Categories

ATC Codes
L01XE02 — Gefitinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolinamines
Alternative Parents
Aniline and substituted anilines / Anisoles / Alkyl aryl ethers / Aminopyrimidines and derivatives / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides / Morpholines / Imidolactams
show 10 more
Substituents
Alkyl aryl ether / Amine / Aminopyrimidine / Aniline or substituted anilines / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinazolines, morpholines (CHEBI:49668)

Chemical Identifiers

UNII
S65743JHBS
CAS number
184475-35-2
InChI Key
XGALLCVXEZPNRQ-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine
SMILES
COC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C1

References

Synthesis Reference
US5770599
General References
  1. 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]
  2. 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]
Human Metabolome Database
HMDB0014462
KEGG Drug
D01977
PubChem Compound
123631
PubChem Substance
46508649
ChemSpider
110217
BindingDB
5447
RxNav
328134
ChEBI
49668
ChEMBL
CHEMBL939
ZINC
ZINC000019632614
Therapeutic Targets Database
DAP000657
PharmGKB
PA131301952
PDBe Ligand
IRE
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gefitinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2ito / 2ity / 2itz / 3ug2 / 4i22 / 4wkq / 5y7z / 5y80
FDA label
Download (80.5 KB)
MSDS
Download (59.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentCaucasian Patients With EGFR Mutation Positive Advanced NSCLC1
4CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
4Not Yet RecruitingTreatmentAdenocarcinomas / Carcinoma NOS / Non-Small Cell Lung Carcinoma (NSCLC)1
4Not Yet RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
4TerminatedTreatmentEGFR Activating Mutation / Metastatic Non-Small Cell Lung Cancer1
4TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
4Unknown StatusTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
3Active Not RecruitingTreatmentLocally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer1
3Active Not RecruitingTreatmentLocally Advanced or Metastatic EGFR Sensitising Mutation Positive Non-small Cell Lung Cancer1
3Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1

Pharmacoeconomics

Manufacturers
  • Astrazeneca uk ltd
Packagers
  • AstraZeneca Inc.
  • Genentech Inc.
Dosage Forms
FormRouteStrength
TabletOral
Tablet, coatedOral250 MG
Tablet, coatedOral250 mg/1
Tablet, film coatedOral
Tablet, film coatedOral250 mg
TabletOral250 mg
Prices
Unit descriptionCostUnit
Tarceva 150 mg tablet163.98USD tablet
Tarceva 100 mg tablet144.98USD tablet
Iressa 250 mg tablet68.08USD tablet
Tarceva 25 mg tablet52.78USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5457105No1995-10-102013-01-19US flag
CA2215732No2002-04-092016-04-23Canada flag
CA2086968No1998-06-232013-01-08Canada flag
US5770599No1998-06-232017-05-05US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySparingly soluble (<pH4)Not Available
logP3.2Not Available
pKa5.4 and 7.2FDA label
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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9961
Blood Brain Barrier+0.9759
Caco-2 permeable+0.5934
P-glycoprotein substrateSubstrate0.693
P-glycoprotein inhibitor IInhibitor0.7361
P-glycoprotein inhibitor IIInhibitor0.923
Renal organic cation transporterInhibitor0.5543
CYP450 2C9 substrateNon-substrate0.7853
CYP450 2D6 substrateNon-substrate0.6447
CYP450 3A4 substrateSubstrate0.6354
CYP450 1A2 substrateInhibitor0.7516
CYP450 2C9 inhibitorNon-inhibitor0.6272
CYP450 2D6 inhibitorNon-inhibitor0.6536
CYP450 2C19 inhibitorInhibitor0.644
CYP450 3A4 inhibitorInhibitor0.8206
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9309
Ames testNon AMES toxic0.5
CarcinogenicityNon-carcinogens0.9218
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5141 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.758
hERG inhibition (predictor II)Inhibitor0.8019
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0193000000-38bb088cc8af6a0e12a4
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-1511900000-d0570bedf59699989575

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
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]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [PubMed:24713129]
  2. Alfieri RR, Galetti M, Tramonti S, Andreoli R, Mozzoni P, Cavazzoni A, Bonelli M, Fumarola C, La Monica S, Galvani E, De Palma G, Mutti A, Mor M, Tiseo M, Mari E, Ardizzoni A, Petronini PG: Metabolism of the EGFR tyrosin kinase inhibitor gefitinib by cytochrome P450 1A1 enzyme in EGFR-wild type non small cell lung cancer cell lines. Mol Cancer. 2011 Nov 23;10:143. doi: 10.1186/1476-4598-10-143. [PubMed:22111840]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Swaisland HC, Cantarini MV, Fuhr R, Holt A: Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics. Clin Pharmacokinet. 2006;45(6):633-44. doi: 10.2165/00003088-200645060-00006. [PubMed:16719544]
  2. Swaisland HC, Ranson M, Smith RP, Leadbetter J, Laight A, McKillop D, Wild MJ: Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Clin Pharmacokinet. 2005;44(10):1067-81. doi: 10.2165/00003088-200544100-00005. [PubMed:16176119]
  3. Suzumura T, Kimura T, Kudoh S, Umekawa K, Nagata M, Matsuura K, Tanaka H, Mitsuoka S, Yoshimura N, Kira Y, Nakai T, Hirata K: Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer. BMC Cancer. 2012 Dec 4;12:568. doi: 10.1186/1471-2407-12-568. [PubMed:23207012]
  4. Takimoto T, Kijima T, Otani Y, Nonen S, Namba Y, Mori M, Yokota S, Minami S, Komuta K, Uchida J, Imamura F, Furukawa M, Tsuruta N, Fujio Y, Azuma J, Tachibana I, Kumanogoh A: Polymorphisms of CYP2D6 gene and gefitinib-induced hepatotoxicity. Clin Lung Cancer. 2013 Sep;14(5):502-7. doi: 10.1016/j.cllc.2013.03.003. Epub 2013 May 9. [PubMed:23664723]
  5. IRESSA (gefitinib) tablets for oral use - FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d 24-hydroxylase 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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. [PubMed:17575239]
  2. Link [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Link [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Link [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
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]

Drug created on June 13, 2005 07:24 / Updated on October 29, 2020 19:25

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