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Identification
NameGefitinib
Accession NumberDB00317  (APRD00997, DB07998)
TypeSmall Molecule
GroupsApproved, 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. [Wikipedia]

Structure
Thumb
Synonyms
4-(3'-chloro-4'-Fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline
Gefitinib
Iressa
N-(3-chloro-4-Fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamine
ZD 1839
External Identifiers
  • ZD1839
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Iressatablet, coated250 mg/1oralAstra Zeneca Pharmaceuticals Lp2015-07-13Not applicableUs
Iressatablet250 mgoralAstrazeneca Canada Inc2003-12-17Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIS65743JHBS
CAS number184475-35-2
WeightAverage: 446.902
Monoisotopic: 446.152096566
Chemical FormulaC22H24ClFN4O3
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Anisole
  • Halobenzene
  • Fluorobenzene
  • Chlorobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Oxazinane
  • Morpholine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Oxacycle
  • Azacycle
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.
PharmacodynamicsGefitinib 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 actionGefitinib 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.
Related Articles
AbsorptionAbsorbed 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 binding90% 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 eliminationElimination 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 life48 hours [IV administration]
Clearance
  • 595 mL/min [IV administration]
ToxicityThe 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
PathwayCategorySMPDB ID
Gefitinib Action PathwayDrug actionSMP00473
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Epidermal growth factor receptor
Gene symbol: EGFR
UniProt: P00533
Not AvailableG719A/C OR (L858R and L861Q)Not AvailableAssociated with enhanced activation of the EGFR tyrosine kinase in patients with non-small cell lung cancer (NSCLC) recieving tyrosine kinase inhibitor therapy.15118073
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
ATP-binding cassette sub-family G member 2
Gene symbol: ABCG2
UniProt: Q9UNQ0
rs2231142 Not AvailableA AlleleDiarrhea17148776
ATP-binding cassette sub-family G member 2
Gene symbol: ABCG2
UniProt: Q9UNQ0
rs2231142 Not AvailableA alleleIn non-small lung cancer patients, those that are heterozygous (ABCG2 421C>A) have a higher risk of diarrhea.17148776
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Astrazeneca uk ltd
Packagers
Dosage forms
FormRouteStrength
Tabletoral250 mg
Tablet, coatedoral250 mg/1
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)
CA2086968 No1998-06-232013-01-08Canada
CA2215732 No2002-04-092016-04-23Canada
US5457105 No1993-01-192013-01-19Us
US5770599 No1997-05-052017-05-05Us
Properties
StateSolid
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

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
ATC CodesL01XE02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (80.5 KB)
MSDSDownload (59.2 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Gefitinib can be increased when it is combined with Abiraterone.
AcenocoumarolGefitinib may increase the anticoagulant activities of Acenocoumarol.
Aluminum hydroxideThe serum concentration of Gefitinib can be decreased when it is combined with Aluminum hydroxide.
AprepitantThe serum concentration of Gefitinib can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Gefitinib.
BexaroteneThe serum concentration of Gefitinib can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Gefitinib can be decreased when it is combined with Bosentan.
Calcium carbonateThe serum concentration of Gefitinib can be decreased when it is combined with Calcium carbonate.
CarbamazepineThe serum concentration of Gefitinib can be decreased when it is combined with Carbamazepine.
CimetidineThe serum concentration of Gefitinib can be decreased when it is combined with Cimetidine.
ConivaptanThe serum concentration of Gefitinib can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Gefitinib can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Gefitinib can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Gefitinib can be decreased when it is combined with Deferasirox.
DicoumarolGefitinib may increase the anticoagulant activities of Dicoumarol.
EltrombopagThe serum concentration of Gefitinib can be increased when it is combined with Eltrombopag.
EnzalutamideThe serum concentration of Gefitinib can be decreased when it is combined with Enzalutamide.
EsomeprazoleThe serum concentration of Gefitinib can be decreased when it is combined with Esomeprazole.
FamotidineThe serum concentration of Gefitinib can be decreased when it is combined with Famotidine.
FluconazoleThe metabolism of Gefitinib can be decreased when combined with Fluconazole.
FluoxetineThe metabolism of Gefitinib can be decreased when combined with Fluoxetine.
FosaprepitantThe serum concentration of Gefitinib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Gefitinib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Gefitinib can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Gefitinib can be increased when it is combined with Idelalisib.
IvacaftorThe serum concentration of Gefitinib can be increased when it is combined with Ivacaftor.
LansoprazoleThe serum concentration of Gefitinib can be decreased when it is combined with Lansoprazole.
LuliconazoleThe serum concentration of Gefitinib can be increased when it is combined with Luliconazole.
Magnesium hydroxideThe serum concentration of Gefitinib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Gefitinib can be decreased when it is combined with Magnesium oxide.
MifepristoneThe serum concentration of Gefitinib can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Gefitinib can be decreased when it is combined with Mitotane.
NelfinavirThe metabolism of Gefitinib can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Gefitinib can be increased when it is combined with Netupitant.
NizatidineThe serum concentration of Gefitinib can be decreased when it is combined with Nizatidine.
OmeprazoleThe serum concentration of Gefitinib can be decreased when it is combined with Omeprazole.
PalbociclibThe serum concentration of Gefitinib can be increased when it is combined with Palbociclib.
PanobinostatThe serum concentration of Gefitinib can be increased when it is combined with Panobinostat.
PantoprazoleThe serum concentration of Gefitinib can be decreased when it is combined with Pantoprazole.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Gefitinib.
Peginterferon alfa-2bThe serum concentration of Gefitinib can be decreased when it is combined with Peginterferon alfa-2b.
PhenobarbitalThe serum concentration of Gefitinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Gefitinib can be decreased when it is combined with Phenytoin.
PrimidoneThe serum concentration of Gefitinib can be decreased when it is combined with Primidone.
RabeprazoleThe serum concentration of Gefitinib can be decreased when it is combined with Rabeprazole.
RanitidineThe serum concentration of Gefitinib can be decreased when it is combined with Ranitidine.
RifabutinThe serum concentration of Gefitinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Gefitinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Gefitinib can be decreased when it is combined with Rifapentine.
RitonavirThe metabolism of Gefitinib can be decreased when combined with Ritonavir.
RolapitantThe serum concentration of Gefitinib can be increased when it is combined with Rolapitant.
SiltuximabThe serum concentration of Gefitinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Gefitinib can be increased when it is combined with Simeprevir.
Sodium bicarbonateThe serum concentration of Gefitinib can be decreased when it is combined with Sodium bicarbonate.
St. John's WortThe serum concentration of Gefitinib can be decreased when it is combined with St. John&#39;s Wort.
StiripentolThe serum concentration of Gefitinib can be increased when it is combined with Stiripentol.
TeriflunomideThe serum concentration of Gefitinib can be increased when it is combined with Teriflunomide.
TiclopidineThe metabolism of Gefitinib can be decreased when combined with Ticlopidine.
TocilizumabThe serum concentration of Gefitinib can be decreased when it is combined with Tocilizumab.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Gefitinib.
VinorelbineGefitinib may increase the neutropenic activities of Vinorelbine.
WarfarinGefitinib may increase the anticoagulant activities of Warfarin.
Food Interactions
  • Avoid fresh grapefruit and its juice during therapy as grapefruit may increase serum product levels.
  • Take without regard to meals.

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, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on ke...
Gene Name:
EGFR
Uniprot ID:
P00533
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
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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 ]
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
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
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. FDA label
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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. FDA label

Transporters

Kind
Protein
Organism
Human
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
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
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 26, 2016 02:10