Identification
- Summary
Gefitinib is a tyrosine kinase inhibitor used as first-line therapy to treat non-small cell lung carcinoma (NSCLC) that meets certain genetic mutation criteria.
- Brand Names
- Iressa
- Generic Name
- Gefitinib
- DrugBank Accession Number
- DB00317
- Background
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
Structure for Gefitinib (DB00317)
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic non-small cell lung cancer •••••••••••• ••••••••• ••••• Treatment of Metastatic non-small cell lung cancer •••••••••••• ••••••••• ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AEpidermal growth factor receptor antagonistHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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.
- Pathways
Pathway Category Gefitinib Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details ATP-binding cassette sub-family G member 2 --- (A;C) A allele ADR Directly Studied Patients with this genotype have an increased risk of diarrhea with gefitinib. Details Epidermal growth factor receptor L858R (G;G) / (G;T) T > G Effect Directly Studied The presence of this polymorphism in EGFR is associated with a higher response rate to gefitinib. Details Epidermal growth factor receptor G719A/C (T;T) / (G;T) / (A;A) / (A;G) / (C;C) / (C;G) G > A or C or T Effect Directly Studied The presence of this polymorphism in EGFR is associated with a higher response rate to gefitinib. Details Epidermal growth factor receptor L861Q (A;A) / (A;T) / (G;G) / (G;T) T > A or G Effect Directly Studied The presence of this polymorphism in EGFR is associated with a higher response rate to gefitinib. Details Cytochrome P450 2D6 CYP2D6*3 Not Available C allele Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*4 Not Available C allele Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Gefitinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Gefitinib can be increased when combined with Abatacept. Abemaciclib Gefitinib may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abiraterone The metabolism of Gefitinib can be decreased when combined with Abiraterone. Acalabrutinib The metabolism of Gefitinib can be decreased when combined with Acalabrutinib. - Food Interactions
- Exercise caution with grapefruit products. Grapefruit is an inhibitor of CYP3A4, the enzyme primarily responsible for metabolizing gefitinib. Coadministration with grapefruit products may decrease gefitinib metabolism and increase plasma concentrations.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Gefitinib Mylan Tablet, film coated 250 mg Oral Mylan Pharmaceuticals Limited 2020-12-16 Not applicable EU 
Gefitinib Mylan Tablet, film coated 250 mg Oral Mylan Pharmaceuticals Limited 2020-12-16 Not applicable EU Iressa Tablet, film coated 250 mg Oral Astra Zeneca Ab 2016-09-08 Not applicable EU Iressa Tablet, coated 250 mg/1 Oral AstraZeneca Pharmaceuticals LP 2015-07-13 Not applicable US 
Iressa Tablet, film coated 250 mg Oral Astra Zeneca Ab 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-gefitinib Tablet 250 mg Oral Apotex Corporation 2017-10-18 Not applicable Canada 
Auro-gefitinib Tablet 250 mg Oral Auro Pharma Inc Not applicable Not applicable Canada Gefitinib Tablet, film coated 250 mg/1 Oral Teva Pharmaceuticals, Inc. 2023-06-21 Not applicable US Gefitinib Tablet, coated 250 mg/1 Oral Qilu Pharmaceutical Co., Ltd. 2023-02-13 Not applicable US Gefitinib Tablet, film coated 250 mg/1 Oral Natco Pharma USA LLC 2023-06-05 Not applicable US
Categories
- ATC Codes
- L01EB01 — Gefitinib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Protein Kinase Inhibitors
- Quinazolines
- Tyrosine Kinase Inhibitors
- 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)
- Affected organisms
- Humans and other mammals
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
- 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. [Article]
- 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. [Article]
- Health Canada Approved Drug Products: Iressa (gefitinib) tablets for oral use [Link]
- EMA Summary of Product Characteristics: Iressa (gefitinib) tablets for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0014462
- KEGG Drug
- D01977
- PubChem Compound
- 123631
- PubChem Substance
- 46508649
- ChemSpider
- 110217
- BindingDB
- 5447
- 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
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Caucasian Patients With EGFR Mutation Positive Advanced NSCLC 1 4 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 1 4 Completed Treatment Non-Small Cell Lung Carcinoma 1 4 Recruiting Treatment Adenocarcinomas / Carcinoma / Non-Small Cell Lung Cancer (NSCLC) 1 4 Terminated Treatment EGFR Activating Mutation / Metastatic Non-Small Cell Lung Cancer 1
Pharmacoeconomics
- Manufacturers
- Astrazeneca uk ltd
- Packagers
- AstraZeneca Inc.
- Genentech Inc.
- Dosage Forms
Form Route Strength Tablet Oral 250 mg/1 Tablet, film coated Oral 250 mg/1 Tablet, film coated Oral Tablet, coated Oral 250 mg Tablet, film coated Oral 250 mg Tablet, film coated Oral 250.00 mg Tablet Oral 250 mg Tablet Oral 250.000 mg Tablet, coated Oral 250 mg/1 Tablet Oral 250.00 mg - Prices
Unit description Cost Unit Tarceva 150 mg tablet 163.98USD tablet Tarceva 100 mg tablet 144.98USD tablet Iressa 250 mg tablet 68.08USD tablet Tarceva 25 mg tablet 52.78USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5457105 No 1995-10-10 2013-01-19 US CA2215732 No 2002-04-09 2016-04-23 Canada CA2086968 No 1998-06-23 2013-01-08 Canada US5770599 No 1998-06-23 2017-05-05 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Sparingly soluble (<pH4) Not Available logP 3.2 Not Available pKa 5.4 and 7.2 FDA label - Predicted Properties
Property Value Source Water Solubility 0.027 mg/mL ALOGPS logP 4.02 ALOGPS logP 3.75 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 16.11 Chemaxon pKa (Strongest Basic) 6.85 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 68.74 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 117.51 m3·mol-1 Chemaxon Polarizability 46.11 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9961 Blood Brain Barrier + 0.9759 Caco-2 permeable + 0.5934 P-glycoprotein substrate Substrate 0.693 P-glycoprotein inhibitor I Inhibitor 0.7361 P-glycoprotein inhibitor II Inhibitor 0.923 Renal organic cation transporter Inhibitor 0.5543 CYP450 2C9 substrate Non-substrate 0.7853 CYP450 2D6 substrate Non-substrate 0.6447 CYP450 3A4 substrate Substrate 0.6354 CYP450 1A2 substrate Inhibitor 0.7516 CYP450 2C9 inhibitor Non-inhibitor 0.6272 CYP450 2D6 inhibitor Non-inhibitor 0.6536 CYP450 2C19 inhibitor Inhibitor 0.644 CYP450 3A4 inhibitor Inhibitor 0.8206 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9309 Ames test Non AMES toxic 0.5 Carcinogenicity Non-carcinogens 0.9218 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5141 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.758 hERG inhibition (predictor II) Inhibitor 0.8019
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 196.3968299 predictedDarkChem Lite v0.1.0 [M-H]- 201.19058 predictedDeepCCS 1.0 (2019) [M+H]+ 196.9885299 predictedDarkChem Lite v0.1.0 [M+H]+ 203.54857 predictedDeepCCS 1.0 (2019) [M+Na]+ 196.3063299 predictedDarkChem Lite v0.1.0 [M+Na]+ 210.93166 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Arteaga CL, Johnson DH: Tyrosine kinase inhibitors-ZD1839 (Iressa). Curr Opin Oncol. 2001 Nov;13(6):491-8. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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
- 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
- Link [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- IRESSA (gefitinib) tablets for oral use - FDA Label [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
- SubstrateInhibitor
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 21, 2024 02:33