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Identification
NameErlotinib
Accession NumberDB00530  (APRD00951)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer.

Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.

Structure
Thumb
Synonyms
[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine
Erlotinib
OSI-774
External Identifiers
  • CP358774
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PMS-erlotinibtablet100 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-erlotinibtablet150 mgoralPharmascience IncNot applicableNot applicableCanada
Tarcevatablet25 mg/1oralGenentech, Inc.2005-04-30Not applicableUs
Tarcevatablet100 mg/1oralAvera Mc Kennan Hospital2015-04-01Not applicableUs
Tarcevatablet100 mg/1oralPhysicians Total Care, Inc.2005-11-21Not applicableUs
Tarcevatablet150 mg/1oralPhysicians Total Care, Inc.2005-10-13Not applicableUs
Tarcevatablet25 mg/1oralPhysicians Total Care, Inc.2005-07-01Not applicableUs
Tarcevatablet150 mgoralHoffmann La Roche Limited2005-07-19Not applicableCanada
Tarcevatablet150 mg/1oralGenentech, Inc.2005-04-30Not applicableUs
Tarcevatablet100 mgoralHoffmann La Roche Limited2005-07-19Not applicableCanada
Tarcevatablet100 mg/1oralGenentech, Inc.2005-04-30Not applicableUs
Tarcevatablet25 mgoralHoffmann La Roche Limited2007-01-05Not applicableCanada
Teva-erlotinibtablet150 mgoralTeva Canada Limited2014-12-08Not applicableCanada
Teva-erlotinibtablet100 mgoralTeva Canada Limited2014-12-08Not applicableCanada
Teva-erlotinibtablet25 mgoralTeva Canada Limited2014-12-08Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Erlotinib Hydrochloride
183319-69-9
Thumb
  • InChI Key: GTTBEUCJPZQMDZ-UHFFFAOYSA-N
  • Monoisotopic Mass: 429.145533978
  • Average Mass: 429.897
DBSALT000064
Categories
UNIIJ4T82NDH7E
CAS number183321-74-6
WeightAverage: 393.4357
Monoisotopic: 393.168856239
Chemical FormulaC22H23N3O4
InChI KeyInChIKey=AAKJLRGGTJKAMG-UHFFFAOYSA-N
InChI
InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
IUPAC Name
N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
SMILES
COCCOC1=C(OCCOC)C=C2C(NC3=CC=CC(=C3)C#C)=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
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
PharmacodynamicsNot Available
Mechanism of actionThe mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.
Related Articles
AbsorptionErlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Solubility decreases pH increases. Smoking also decrease the exposure of erlotinib.
Volume of distribution

Apparent volume of distribution = 232 L

Protein binding93% protein bound to albumin and alpha-1 acid glycoprotein (AAG)
Metabolism

Metabolism occurs in the liver. In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.

Route of eliminationFollowing a 100 mg oral dose, 91% of the dose was recovered in which 83% was in feces (1% of the dose as unchanged parent compound) and 8% in urine (0.3% of the dose as unchanged parent compound).
Half lifeMedian half-life of 36.2 hours.
Clearance

Smokers have a 24% higher rate of erlotinib clearance.

ToxicitySymptoms of overdose include diarrhea, rash, and liver transaminase elevation. The most common adverse reactions (>50%) in NSCLC are rash, diarrhea, anorexia and fatigue. The most common adverse reactions (>50%) in pancreatic cancer are fatigue, rash, nausea and anorexia.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Erlotinib Action PathwayDrug actionSMP00472
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 ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9359
Blood Brain Barrier+0.9376
Caco-2 permeable+0.5737
P-glycoprotein substrateSubstrate0.5982
P-glycoprotein inhibitor IInhibitor0.5958
P-glycoprotein inhibitor IINon-inhibitor0.6169
Renal organic cation transporterNon-inhibitor0.7171
CYP450 2C9 substrateNon-substrate0.7942
CYP450 2D6 substrateNon-substrate0.7611
CYP450 3A4 substrateSubstrate0.5886
CYP450 1A2 substrateInhibitor0.7826
CYP450 2C9 inhibitorNon-inhibitor0.5739
CYP450 2D6 inhibitorNon-inhibitor0.6329
CYP450 2C19 inhibitorInhibitor0.598
CYP450 3A4 inhibitorInhibitor0.7194
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7911
Ames testAMES toxic0.5195
CarcinogenicityNon-carcinogens0.9551
BiodegradationNot ready biodegradable0.9907
Rat acute toxicity2.3958 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8158
hERG inhibition (predictor II)Non-inhibitor0.6776
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Osi pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral100 mg/1
Tabletoral100 mg
Tabletoral150 mg/1
Tabletoral150 mg
Tabletoral25 mg/1
Tabletoral25 mg
Prices
Unit descriptionCostUnit
Tarceva 150 mg tablet163.98USD tablet
Tarceva 100 mg tablet144.98USD 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)
CA2216796 No2003-09-022015-06-06Canada
CA2514977 No2010-06-222024-02-11Canada
US5747498 Yes1999-05-082019-05-08Us
US6900221 Yes2001-05-092021-05-09Us
US7087613 Yes2001-05-092021-05-09Us
USRE41065 Yes1999-05-082019-05-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityVery slightly soluble (hydrochloride salt - maximal solubility of approximately 0.4 mg/mL occurs at a pH of approximately 2)Not Available
logP2.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00891 mg/mLALOGPS
logP3.13ALOGPS
logP3.2ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)16.14ChemAxon
pKa (Strongest Basic)4.59ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area74.73 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity107.79 m3·mol-1ChemAxon
Polarizability43.48 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

DrugSyn.org

US5747498
General References
  1. Raymond E, Faivre S, Armand JP: Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000;60 Suppl 1:15-23; discussion 41-2. [PubMed:11129168 ]
  2. Li Z, Xu M, Xing S, Ho WT, Ishii T, Li Q, Fu X, Zhao ZJ: Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. J Biol Chem. 2007 Feb 9;282(6):3428-32. Epub 2006 Dec 18. [PubMed:17178722 ]
  3. Dudek AZ, Kmak KL, Koopmeiners J, Keshtgarpour M: Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. 2006 Jan;51(1):89-96. Epub 2005 Nov 14. [PubMed:16290256 ]
  4. Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI: Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer. 2004 Dec;11(4):793-814. [PubMed:15613453 ]
  5. Blum G, Gazit A, Levitzki A: Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry. 2000 Dec 26;39(51):15705-12. [PubMed:11123895 ]
External Links
ATC CodesL01XE03
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (999 KB)
MSDSDownload (107 KB)
Interactions
Drug Interactions
Drug
Aluminum hydroxideThe serum concentration of Erlotinib can be decreased when it is combined with Aluminum hydroxide.
AprepitantThe serum concentration of Erlotinib can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Erlotinib can be increased when it is combined with Atazanavir.
BexaroteneThe serum concentration of Erlotinib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Erlotinib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Erlotinib can be decreased when it is combined with Bosentan.
Calcium carbonateThe serum concentration of Erlotinib can be decreased when it is combined with Calcium carbonate.
CarbamazepineThe serum concentration of Erlotinib can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Erlotinib can be increased when it is combined with Ceritinib.
CimetidineThe serum concentration of Erlotinib can be decreased when it is combined with Cimetidine.
CiprofloxacinThe serum concentration of Erlotinib can be increased when it is combined with Ciprofloxacin.
ClarithromycinThe serum concentration of Erlotinib can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Erlotinib can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Erlotinib can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Erlotinib can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Erlotinib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Erlotinib can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Erlotinib can be decreased when it is combined with Deferasirox.
EnzalutamideThe serum concentration of Erlotinib can be decreased when it is combined with Enzalutamide.
EsomeprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Esomeprazole.
FamotidineThe serum concentration of Erlotinib can be decreased when it is combined with Famotidine.
FluconazoleThe metabolism of Erlotinib can be decreased when combined with Fluconazole.
FluvoxamineThe serum concentration of Erlotinib can be increased when it is combined with Fluvoxamine.
FosaprepitantThe serum concentration of Erlotinib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Erlotinib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Erlotinib can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Erlotinib can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Erlotinib can be increased when it is combined with Indinavir.
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Erlotinib.
ItraconazoleThe serum concentration of Erlotinib can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Erlotinib can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Erlotinib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Lansoprazole.
LuliconazoleThe serum concentration of Erlotinib can be increased when it is combined with Luliconazole.
Magnesium hydroxideThe serum concentration of Erlotinib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Erlotinib can be decreased when it is combined with Magnesium oxide.
MifepristoneThe serum concentration of Erlotinib can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Erlotinib can be decreased when it is combined with Mitotane.
NefazodoneThe serum concentration of Erlotinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Erlotinib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Erlotinib can be increased when it is combined with Netupitant.
NizatidineThe serum concentration of Erlotinib can be decreased when it is combined with Nizatidine.
OmeprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Omeprazole.
PalbociclibThe serum concentration of Erlotinib can be increased when it is combined with Palbociclib.
PantoprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Pantoprazole.
PhenobarbitalThe serum concentration of Erlotinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Erlotinib can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Erlotinib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Erlotinib can be decreased when it is combined with Primidone.
RabeprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Rabeprazole.
RanitidineThe serum concentration of Erlotinib can be decreased when it is combined with Ranitidine.
RifabutinThe serum concentration of Erlotinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Erlotinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Erlotinib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Erlotinib can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Erlotinib can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Erlotinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Erlotinib can be increased when it is combined with Simeprevir.
Sodium bicarbonateThe serum concentration of Erlotinib can be decreased when it is combined with Sodium bicarbonate.
St. John's WortThe serum concentration of Erlotinib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Erlotinib can be increased when it is combined with Stiripentol.
TelaprevirThe serum concentration of Erlotinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Erlotinib can be increased when it is combined with Telithromycin.
TocilizumabThe serum concentration of Erlotinib can be decreased when it is combined with Tocilizumab.
VoriconazoleThe serum concentration of Erlotinib can be increased when it is combined with Voriconazole.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Erlotinib.
Food Interactions
  • Take at least 1 hour before or 2 hours after any food.
  • Take with a glass of water.

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. Kim TE, Murren JR: Erlotinib OSI/Roche/Genentech. Curr Opin Investig Drugs. 2002 Sep;3(9):1385-95. [PubMed:12498017 ]
  2. Laird AD, Cherrington JM: Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs. 2003 Jan;12(1):51-64. [PubMed:12517254 ]
  3. Delbaldo C, Faivre S, Raymond E: [Epidermal growth factor inhibitors]. Rev Med Interne. 2003 Jun;24(6):372-83. [PubMed:12814826 ]
  4. Bulgaru AM, Mani S, Goel S, Perez-Soler R: Erlotinib (Tarceva): a promising drug targeting epidermal growth factor receptor tyrosine kinase. Expert Rev Anticancer Ther. 2003 Jun;3(3):269-79. [PubMed:12820772 ]
  5. Akita RW, Sliwkowski MX: Preclinical studies with Erlotinib (Tarceva). Semin Oncol. 2003 Jun;30(3 Suppl 7):15-24. [PubMed:12840797 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and is...
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
References
  1. Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [PubMed:18839173 ]
  2. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]

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. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. [PubMed:16166415 ]
  3. 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 ]
  4. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. [PubMed:16609030 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. 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
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. Lu JF, Eppler SM, Wolf J, Hamilton M, Rakhit A, Bruno R, Lum BL: Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure-safety relationship in patients with non-small cell lung cancer. Clin Pharmacol Ther. 2006 Aug;80(2):136-45. [PubMed:16890575 ]
  3. Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. [PubMed:16166415 ]
  4. 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 ]
  5. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. [PubMed:16609030 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. [PubMed:16166415 ]
  3. 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
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. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. 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:
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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. [PubMed:16609030 ]
Kind
Protein
Organism
Human
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 unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compou...
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  2. 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
inhibitor
General Function:
Steroid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular Weight:
59590.91 Da
References
  1. Liu Y, Ramirez J, House L, Ratain MJ: The UGT1A1*28 polymorphism correlates with erlotinib's effect on SN-38 glucuronidation. Eur J Cancer. 2010 Jul;46(11):2097-103. doi: 10.1016/j.ejca.2010.04.022. Epub 2010 May 23. [PubMed:20580994 ]

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
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

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
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 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. 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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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. Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH: Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7. doi: 10.1158/1535-7163.MCT-07-2250. [PubMed:18723475 ]
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Drug created on June 13, 2005 07:24 / Updated on August 24, 2016 03:05