Identification

Name
Gefitinib
Accession Number
DB00317  (APRD00997, DB07998)
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
Synonyms
  • 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline
  • N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamine
External IDs
ZD 1839 / ZD-1839 / ZD1839
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IressaTablet, coated250 mg/1OralAstraZeneca Pharmaceuticals LP2015-07-13Not applicableUs
IressaTablet250 mgOralAstra Zeneca2003-12-17Not applicableCanada
IressaTablet, film coated250 mgOralAstra Zeneca Ab2009-06-24Not applicableEu
IressaTablet, film coated250 mgOralAstra Zeneca Ab2009-06-24Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-gefitinibTablet250 mgOralApotex Corporation2017-10-18Not applicableCanada
International/Other Brands
Iressa
Categories
UNII
S65743JHBS
CAS number
184475-35-2
Weight
Average: 446.902
Monoisotopic: 446.152096566
Chemical Formula
C22H24ClFN4O3
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

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
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 inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. Overexpression leads to inappropriate activation of the apoptotic Ras signal transduction cascade, eventually leading to uncontrolled cell proliferation.

TargetActionsOrganism
AEpidermal growth factor receptor
antagonist
Human
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]
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
DrugInteraction
(R)-warfarinGefitinib may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinGefitinib may increase the anticoagulant activities of (S)-Warfarin.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Gefitinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Gefitinib.
4-hydroxycoumarinGefitinib may increase the anticoagulant activities of 4-hydroxycoumarin.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Gefitinib.
6-Deoxyerythronolide BThe metabolism of Gefitinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Gefitinib.
AbemaciclibAbemaciclib may decrease the excretion rate of Gefitinib which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Gefitinib.
Food Interactions
  • Avoid fresh grapefruit and its juice during therapy as grapefruit may increase serum product levels.
  • Take without regard to meals.

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]
External Links
Human Metabolome Database
HMDB0014462
KEGG Drug
D01977
PubChem Compound
123631
PubChem Substance
46508649
ChemSpider
110217
BindingDB
5447
ChEBI
49668
ChEMBL
CHEMBL939
Therapeutic Targets Database
DAP000657
PharmGKB
PA131301952
HET
IRE
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gefitinib
ATC Codes
L01XE02 — 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
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Patients With Non-Small Cell Lung Cancer(NSCLC)1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Tumors, Solid1
1CompletedOtherBioequivalence Study1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentAdvanced Tumor1
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentColorectal Cancers1
1CompletedTreatmentHead and Neck Carcinoma2
1CompletedTreatmentHead and Neck Carcinoma / Squamous Cell Carcinoma (SCC)1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)4
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Lymphomas / Tumors, Solid1
1CompletedTreatmentLung Cancers2
1CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
1CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1CompletedTreatmentTumors1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific3
1CompletedTreatmentUnspecified Childhood Solid Tumor, Protocol Specific1
1RecruitingNot AvailableLung Cancers1
1RecruitingTreatmentEGFR-mutant Non-small Cell Lung Cancer1
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
1TerminatedTreatmentEsophageal Cancers1
1TerminatedTreatmentStage III Squamous Cell Carcinoma of the Hypopharynx / Stage III Squamous Cell Carcinoma of the Larynx / Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage III Squamous Cell Carcinoma of the Oropharynx / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Oropharynx1
1Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentAbdominal wall neoplasm / Cancer of the Ovary / Fallopian Tube Cancer1
1, 2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1, 2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma1
1, 2CompletedTreatmentBrain and Central Nervous System Tumors / Prostate Cancer1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentCarcinoma, Non-Small Cell-Lung / Lung Cancers / Neoplasms, Lung / Respiratory Tract Neoplasms1
1, 2CompletedTreatmentColorectal Cancers2
1, 2CompletedTreatmentHead and Neck Carcinoma1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentLung Cancers3
1, 2CompletedTreatmentMalignant Neoplasm of Pancreas1
1, 2CompletedTreatmentNasopharyngeal Carcinoma1
1, 2CompletedTreatmentNeoplasms, Head and Neck1
1, 2CompletedTreatmentNon-Metastatic Prostate Cancer1
1, 2CompletedTreatmentRenal Cell Adenocarcinoma1
1, 2CompletedTreatmentUntreated Childhood Anaplastic Astrocytoma / Untreated Childhood Anaplastic Oligodendroglioma / Untreated Childhood Brain Stem Glioma / Untreated Childhood Giant Cell Glioblastoma / Untreated Childhood Glioblastoma / Untreated Childhood Gliomatosis Cerebri / Untreated Childhood Gliosarcoma / Untreated Childhood Oligodendroglioma1
1, 2Not Yet RecruitingTreatmentEGFR Mutation Positive Non Small Cell Lung Cancer1
1, 2TerminatedTreatmentColorectal Cancers1
1, 2TerminatedTreatmentEsophageal Cancers1
1, 2TerminatedTreatmentHead and Neck Carcinoma1
1, 2TerminatedTreatmentSubjects With Resectable Local or Locally Advanced, Non-Metastatic (T2-T4, N0-N3, M0; Stages II and III) and Histologically-Confirmed Intestinal GC1
1, 2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Unknown StatusTreatmentNon-Melanomatous Skin Cancer1
1, 2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2WithdrawnTreatmentLung Cancers1
2Active Not RecruitingTreatmentHead and Neck Carcinoma1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentNeoplasms, Lung1
2CompletedNot AvailableProstate Cancer1
2CompletedDiagnosticNonresectable Adrenocortical Carcinoma1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML)1
2CompletedTreatmentAdenocarcinoma of the Lung / Adenosquamous Cell Lung Cancer / Bronchoalveolar Cell Lung Cancer / Large Cell Lung Cancer / Squamous Cell Carcinoma of Lung / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer1
2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma1
2CompletedTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer1
2CompletedTreatmentAdvanced Malignant Mesothelioma / Epithelial Mesothelioma / Recurrent Malignant Mesothelioma / Sarcomatous Mesothelioma1
2CompletedTreatmentBladder Cancers1
2CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
2CompletedTreatmentBrain and Central Nervous System Tumors2
2CompletedTreatmentBronchioloalveolar Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
2CompletedTreatmentBronchoalveolar Cell Lung Cancer / Non-Small Cell Lung Cancer Recurrent / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2CompletedTreatmentCancer of Head and Neck1
2CompletedTreatmentCancer of Head and Neck / Squamous Cell Cancer1
2CompletedTreatmentCancer of the Fallopian Tube / Cancer of the Ovary / Malignant Peritoneal Neoplasm1
2CompletedTreatmentCancer of the Ovary / Cervical Cancers / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentCancer of the Ovary / Primary Peritoneal Cancer / Tubal Carcinoma1
2CompletedTreatmentCancer of the Ovary / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentCancer, Advanced / EGFR Gene Amplification / Lung Cancer Non-Small Cell Cancer (NSCLC) / Stage IIIB NSCLC / Stage IV NSCLC1
2CompletedTreatmentCancer, Breast12
2CompletedTreatmentCancers1
2CompletedTreatmentColorectal Cancers3
2CompletedTreatmentEsophageal Cancers3
2CompletedTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2CompletedTreatmentEstrogen Receptor-Positive Breast Cancer / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentGastrinoma / Glucagonoma / Insulinoma / Metastatic Gastrointestinal Carcinoid Tumor / Pancreatic Polypeptide Tumor / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Islet Cell Carcinoma / Somatostatinoma / WDHA Syndrome1
2CompletedTreatmentGlioblastomas1
2CompletedTreatmentHead and Neck Carcinoma7
2CompletedTreatmentLocally Advanced Prostate Cancer1
2CompletedTreatmentLocally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV1
2CompletedTreatmentLung Adenocarcinoma With Bronchiolo-alveolar Feature / Pneumonic-type Adenocarcinoma (P-ADC)1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)14
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2CompletedTreatmentLung Cancers9
2CompletedTreatmentLung Cancers / Metastatic Cancers1
2CompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentMesothelioma1
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentMetastatic Pancreatic Carcinoma1
2CompletedTreatmentMetastatic Transitional Cell Cancer of the Renal Pelvis and Ureter / Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter1
2CompletedTreatmentNeoplasms, Breast2
2CompletedTreatmentNeoplasms, Head and Neck1
2CompletedTreatmentNeoplasms, Squamous Cell1
2CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentPrevious Treated Metastatic Non-small Cell Lung Cancer1
2CompletedTreatmentProstate Cancer4
2CompletedTreatmentPulmonary Cancer1
2CompletedTreatmentRecurrent Skin Cancer / Squamous Cell Carcinoma of the Skin1
2CompletedTreatmentRecurrent Uterine Corpus Carcinoma1
2CompletedTreatmentRenal Cancers3
2CompletedTreatmentSalivary Gland Cancers1
2CompletedTreatmentSarcomas1
2CompletedTreatmentSkin Cancers1
2Not Yet RecruitingTreatmentAdenocarcinoma of the Lung1
2Not Yet RecruitingTreatmentAdenocarcinoma of the Lung / EGFR Positive Non-small Cell Lung Cancer1
2Not Yet RecruitingTreatmentEGFR Gene Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2Not Yet RecruitingTreatmentEGFR-sensitive Mutation-positive Advanced Non-squamous Non-small Cell Lung Cancer Treated With S-1plus Gefitinib Versus Gefitinib Monotherapy1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentAdenocarcinoma of the Lung1
2RecruitingTreatmentCholangiocarcinoma of the Extrahepatic Bile Duct / Gallbladder Cancer1
2RecruitingTreatmentCorticotrophin Adenoma / Cushing's Disease1
2RecruitingTreatmentEGFR Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Brain Tumors1
2RecruitingTreatmentEffects of Chemotherapy / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2RecruitingTreatmentLung Cancers1
2RecruitingTreatmentRare Tumor / Refractory Tumors1
2RecruitingTreatmentStage IV Lung Cancer1
2RecruitingTreatmentTumors, Solid1
2SuspendedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentAdenocarcinoma of the Colon / Adenocarcinoma of the Rectum / Metastatic Colon Cancer / Mucinous Adenocarcinoma of the Colon / Mucinous Adenocarcinoma of the Rectum / Recurrent Colon Cancer / Recurrent Rectal Cancer / Signet Ring Adenocarcinoma of the Colon / Signet Ring Adenocarcinoma of the Rectum / Stage IV Rectal Cancer1
2TerminatedTreatmentBladder Cancers1
2TerminatedTreatmentCancer, Breast3
2TerminatedTreatmentEsophageal Cancers2
2TerminatedTreatmentGlioblastomas1
2TerminatedTreatmentHead and Neck Carcinoma1
2TerminatedTreatmentHead and Neck Carcinoma / Lung Cancers1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms, Brain1
2TerminatedTreatmentProstate Cancer1
2Unknown StatusPreventionLiver Cancer1
2Unknown StatusTreatmentAdenocarcinomas / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2Unknown StatusTreatmentBrain Metastasis / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2Unknown StatusTreatmentCancer, Breast1
2Unknown StatusTreatmentEsophageal Cancers1
2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)6
2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Toxicity1
2Unknown StatusTreatmentLung Cancers2
2Unknown StatusTreatmentSquamous Cell Carcinoma of Bronchus1
2WithdrawnTreatmentCancer, Breast1
2WithdrawnTreatmentHead and Neck Carcinoma / Squamous Cell Carcinoma (SCC)1
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2WithdrawnTreatmentMetastatic Colorectal Cancers1
2, 3CompletedTreatmentColorectal Cancers1
2, 3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2, 3Not Yet RecruitingTreatmentEGFR Gene Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Brain Tumors1
2, 3Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2, 3RecruitingTreatmentEGFR Gene Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC) / Metastatic Brain Tumors1
2, 3TerminatedTreatmentActivating EGFR Mutation / Lung Cancer Non-Small Cell Cancer (NSCLC) / Non-squamous Non-small Cell Lung Cancer Stage II / Non-squamous Non-small Cell Lung Cancer Stage IIIA / Non-squamous Non-small Cell Lung Cancer Stage IIIB1
2, 3Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Active Not RecruitingTreatmentEGFR Positive Non-small Cell Lung Cancer1
3Active Not RecruitingTreatmentLocally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
3CompletedTreatmentAdenocarcinoma of the Lung / Adenosquamous Cell Lung Cancer / Bronchoalveolar Cell Lung Cancer / Large Cell Lung Cancer / Squamous Cell Carcinoma of Lung / Stage IB Non-small Cell Lung Cancer / Stage IIA Non-small Cell Lung Cancer / Stage IIB Non-small Cell Lung Cancer / Stage IIIA Non-Small Cell Lung Cancer1
3CompletedTreatmentAdenocarcinoma of the Lung / Bronchoalveolar Cell Lung Cancer / Large Cell Lung Cancer / Squamous Cell Carcinoma of Lung / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer1
3CompletedTreatmentCancer, Breast / Lung Cancers1
3CompletedTreatmentCancers1
3CompletedTreatmentCarcinoma NOS / Metastases / Neoplasms / Non-Small-Cell Lung1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)8
3CompletedTreatmentLung Cancers1
3CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
3CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
3CompletedTreatmentThoracic Neoplasms1
3Enrolling by InvitationTreatmentCancers2
3Not Yet RecruitingTreatment2-year Disease-Free Survival1
3Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingTreatmentEGFR Tyrosine Kinase Inhibitors Plus VEGFR Inhibitors1
3RecruitingTreatmentEGFR / Lung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
3RecruitingTreatmentNeoplasms, Lung1
3TerminatedTreatmentBladder Cancers1
3TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3TerminatedTreatmentLung Cancers1
3TerminatedTreatmentMetastatic Head and Neck Cancer / Recurrent Head and Neck Cancer1
3TerminatedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
3Unknown StatusPreventionLung Cancer Non-Small Cell Cancer (NSCLC)1
3Unknown StatusPreventionLung Cancers1
3Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Unknown StatusTreatmentLung Cancers2
3WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
4CompletedTreatmentCancer of the Head and Neck (H&N) / Cancers of the Head and Neck / Lung Cancer Non-Small Cell Cancer (NSCLC)1
4CompletedTreatmentCaucasian Patients With EGFR Mutation Positive Advanced NSCLC1
4CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
4CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
4RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
4TerminatedTreatmentEGFR Activating Mutation / Metastatic Non-Small Cell Lung Cancer1
4TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableActive Not RecruitingTreatmentAdenocarcinoma of the Lung1
Not AvailableApproved for MarketingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableCompletedNot AvailableIs Targeted Therapy Increasing Survival Inoperable Nonsmall Cell Lung Cancer With Spinal Metastasis ?1
Not AvailableCompletedTreatmentAnaplastic Thyroid Cancers / Insular Thyroid Cancer / Metastatic Parathyroid Cancer / Non-Small Cell Lung Cancer Recurrent / Recurrent Adenoid Cystic Carcinoma of the Oral Cavity / Recurrent Basal Cell Carcinoma of the Lip / Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity / Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity / Recurrent Lymphoepithelioma of the Nasopharynx / Recurrent Lymphoepithelioma of the Oropharynx / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity / Recurrent Mucoepidermoid Carcinoma of the Oral Cavity / Recurrent Parathyroid Cancer / Recurrent Salivary Gland Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Thyroid Cancer / Recurrent Verrucous Carcinoma of the Larynx / Stage III Follicular Thyroid Cancer / Stage III Papillary Thyroid Cancer / Stage III Salivary Gland Cancer / Stage III Squamous Cell Carcinoma of the Hypopharynx / Stage III Squamous Cell Carcinoma of the Larynx / Stage III Verrucous Carcinoma of the Larynx / Stage IIIb Non-small Cell Lung Cancer / Stage IV Lymphoepithelioma of the Nasopharynx / Stage IV Non-Small Cell Lung Cancer / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity / Stage IVA Basal Cell Carcinoma of the Lip / Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity / Stage IVA Follicular Thyroid Cancer / Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity / Stage IVA Lymphoepithelioma of the Oropharynx / Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity / Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity / Stage IVA Papillary Thyroid Cancer / Stage IVA Salivary Gland Cancer / Stage IVA Squamous Cell Carcinoma of the Larynx / Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVA Squamous Cell Carcinoma of the Oropharynx / Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVA Verrucous Carcinoma of the Larynx / Stage IVA Verrucous Carcinoma of the Oral Cavity / Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity / Stage IVB Basal Cell Carcinoma of the Lip / Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity / Stage IVB Follicular Thyroid Cancer / Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity / Stage IVB Lymphoepithelioma of the Oropharynx / Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity / Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity / Stage IVB Papillary Thyroid Cancer / Stage IVB Salivary Gland Cancer / Stage IVB Squamous Cell Carcinoma of the Larynx / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Oropharynx / Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVB Verrucous Carcinoma of the Larynx / Stage IVB Verrucous Carcinoma of the Oral Cavity / Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity / Stage IVC Basal Cell Carcinoma of the Lip / Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity / Stage IVC Follicular Thyroid Cancer / Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity / Stage IVC Lymphoepithelioma of the Oropharynx / Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity / Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity / Stage IVC Papillary Thyroid Cancer / Stage IVC Salivary Gland Cancer / Stage IVC Squamous Cell Carcinoma of the Larynx / Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVC Squamous Cell Carcinoma of the Oropharynx / Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVC Verrucous Carcinoma of the Larynx / Stage IVC Verrucous Carcinoma of the Oral Cavity / Thryoid Gland Nonmedullary Carcinoma / Thyroid Gland Medullary Carcinoma / Tongue Cancer / Untreated Metastatic Squamous Neck Cancer With Occult Primary1
Not AvailableCompletedTreatmentErlotinib / Lung Cancer Non-Small Cell Cancer (NSCLC) / Non-Small-Cell Lung1
Not AvailableCompletedTreatmentOveral Survival, Non-small Cell Lung Cancer1
Not AvailableNot Yet RecruitingTreatmentLung Cancers1
Not AvailableNot Yet RecruitingTreatmentNon-Squamous Non-Small Cell Lung Cancer1
Not AvailableRecruitingOtherEGFR Gene Mutations / Non-Small Cell Adenocarcinoma / Tyrosine kinase mutation1
Not AvailableTerminatedTreatmentBrain Metastasis / EGFR-mutated Lung Adenocarcinoma1
Not AvailableTerminatedTreatmentLung Cancers1
Not AvailableUnknown StatusDiagnosticEGFR Mutation Positive Non-small Cell Lung Cancer1

Pharmacoeconomics

Manufacturers
  • Astrazeneca uk ltd
Packagers
  • AstraZeneca Inc.
  • Genentech Inc.
Dosage forms
FormRouteStrength
TabletOral250 mg
Tablet, coatedOral250 mg/1
Tablet, film coatedOral250 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)
US5457105No1993-01-192013-01-19Us
CA2215732No2002-04-092016-04-23Canada
CA2086968No1998-06-232013-01-08Canada
US5770599No1997-05-052017-05-05Us

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

Taxonomy

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
Quinazolinamine / Anisole / Aniline or substituted anilines / Alkyl aryl ether / Aminopyrimidine / Chlorobenzene / Fluorobenzene / Halobenzene / Aryl chloride / Aryl fluoride
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinazolines, morpholines (CHEBI:49668)

Targets

Kind
Protein
Organism
Human
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
Human
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. 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]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. 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]
  2. 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]
  3. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Human
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
Human
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
Human
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
Human
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
Human
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
Human
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
Human
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 16, 2018 08:25