Erlotinib

Identification

Summary

Erlotinib is an EGFR tyrosine kinase inhibitor used to treat certain small cell lung cancers or advanced metastatic pancreatic cancers.

Brand Names
Tarceva
Generic Name
Erlotinib
DrugBank Accession Number
DB00530
Background

Erlotinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that is used in the treatment of non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is typically marketed under the trade name Tarceva. Erlotinib binds to the epidermal growth factor receptor (EGFR) tyrosine kinase in a reversible fashion at the adenosine triphosphate (ATP) binding site of the receptor. Recent studies demonstrate that erlotinib is also a potent inhibitor of JAK2V617F, which is a mutant form of tyrosine kinase JAK2 found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. This finding introduces the potential use of erlotinib in the treatment of JAK2V617F-positive PV and other myeloproliferative disorders.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 393.4357
Monoisotopic: 393.168856239
Chemical Formula
C22H23N3O4
Synonyms
  • [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine
  • Erlotinib
External IDs
  • CP-358,774
  • CP-358774
  • CP-35877401
  • CP358774
  • R-1415
  • RG-1415

Pharmacology

Indication

Erlotinib is indicated for:

  • The treatment of metastatic non-small cell lung cancer (NSCLC) with tumors showing epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations Label.

  • In combination with first-line treatment for patients diagnosed with locally advanced, unresectable or metastatic pancreatic cancer Label.

The safety and efficacy of erlotinib have not been established for patients with NSCLC whose tumors show other EGFR mutations. Additionally it is not recommended for use in combination with platinum-based chemotherapy. Label

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatLocally advanced pancreatic cancerRegimen in combination with: Gemcitabine (DB00441)••••••••••••••••••••• •••••
Treatment ofMetastatic non-small cell lung cancer••••••••••••••••••• ••••••••••• ••••• ••••••••••••
Used in combination to treatMetastatic pancreatic cancerRegimen in combination with: Gemcitabine (DB00441)••••••••••••••••••••• •••••
Used in combination to treatUnresectable pancreatic cancerRegimen in combination with: Gemcitabine (DB00441)••••••••••••••••••••• •••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

The 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.

TargetActionsOrganism
ANuclear receptor subfamily 1 group I member 2
agonist
Humans
AEpidermal growth factor receptor
antagonist
Humans
Absorption

Erlotinib 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 binding

93% 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.

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Route of elimination

Following 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-life

Median half-life of 36.2 hours.

Clearance

Smokers have a 24% higher rate of erlotinib clearance.

Adverse Effects
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Toxicity

Symptoms 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.

Pathways
PathwayCategory
Erlotinib Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
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 erlotinib.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 erlotinib.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 erlotinib.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Erlotinib.
AbametapirThe serum concentration of Erlotinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Erlotinib can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Erlotinib.
AbirateroneThe metabolism of Erlotinib can be decreased when combined with Abiraterone.
Food Interactions
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of erlotinib.
  • Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of erlotinib.
  • Take on an empty stomach. Food increases erlotinib bioavailability, therefore administer at least 1 hour before or 2 hours after meals.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Erlotinib hydrochlorideDA87705X9K183319-69-9GTTBEUCJPZQMDZ-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TarcevaTablet, film coated150 mgOralRoche Registration Gmb H2016-09-08Not applicableEU flag
TarcevaTablet150 mgOralHoffmann La Roche2005-07-19Not applicableCanada flag
TarcevaTablet100 mg/1OralAvera McKennan Hospital2015-04-012017-05-24US flag
TarcevaTablet25 mg/1OralGenentech, Inc.2005-04-30Not applicableUS flag
TarcevaTablet, film coated100 mgOralRoche Registration Gmb H2016-09-08Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-erlotinibTablet100 mgOralApotex Corporation2017-08-22Not applicableCanada flag
Apo-erlotinibTablet25 mgOralApotex Corporation2017-08-22Not applicableCanada flag
Apo-erlotinibTablet150 mgOralApotex Corporation2017-08-22Not applicableCanada flag
ErlotinibTablet, film coated150 mg/1OralAreva Pharmaceuticals2020-05-01Not applicableUS flag
ErlotinibTablet, film coated100 mg/1OralSun Pharmaceutical Industries, Inc.2019-11-05Not applicableUS flag

Categories

ATC Codes
L01EB02 — Erlotinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolinamines
Alternative Parents
Aniline and substituted anilines / Aminopyrimidines and derivatives / Alkyl aryl ethers / Imidolactams / Heteroaromatic compounds / Secondary amines / Dialkyl ethers / Azacyclic compounds / Acetylides / Organopnictogen compounds
show 1 more
Substituents
Acetylide / Alkyl aryl ether / Amine / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Dialkyl ether / Ether
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
terminal acetylenic compound, quinazolines (CHEBI:114785)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
J4T82NDH7E
CAS number
183321-74-6
InChI Key
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=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2

References

Synthesis Reference
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Blum G, Gazit A, Levitzki A: Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry. 2000 Dec 26;39(51):15705-12. [Article]
Human Metabolome Database
HMDB0014671
KEGG Drug
D07907
PubChem Compound
176870
PubChem Substance
46508021
ChemSpider
154044
BindingDB
5446
RxNav
337525
ChEBI
114785
ChEMBL
CHEMBL553
ZINC
ZINC000001546066
Therapeutic Targets Database
DAP001010
PharmGKB
PA134687924
PDBe Ligand
AQ4
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Erlotinib
PDB Entries
1m17 / 4hjo / 6dwn
FDA label
Download (470 KB)
MSDS
Download (107 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Osi pharmaceuticals inc
Packagers
  • F Hoffmann-La Roche Ltd.
  • Genentech Inc.
  • OSI Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Schwarz Pharma Inc.
Dosage Forms
FormRouteStrength
Tablet, film coatedOral100.00 mg
TabletOral109.267 mg
Tablet, film coatedOral100.000 mg
Tablet, film coatedOral25.000 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral100 MG
Tablet, film coatedOral25 MG
Tablet, film coatedOral150.00 mg
TabletOral163.90 mg
TabletOral
TabletOral100 mg
TabletOral100 mg/1
TabletOral150 mg
TabletOral150 mg/1
TabletOral25 mg/1
TabletOral25 mg
Tablet, film coatedOral
Tablet, film coatedOral109.29 MG
Tablet, film coatedOral163.93 MG
TabletOral27.32 mg
TabletOral25.000 mg
Tablet, film coatedOral150 mg
Tablet, coatedOral100 mg
Tablet, coatedOral150 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)Region
CA2514977No2010-06-222024-02-11Canada flag
CA2216796No2003-09-022015-06-06Canada flag
US7087613Yes2006-08-082021-05-09US flag
US5747498Yes1998-05-052019-05-08US flag
US6900221Yes2005-05-312021-05-09US flag
USRE41065Yes2009-12-292019-05-08US flag

Properties

State
Solid
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)4.62Chemaxon
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 RuleNoChemaxon
MDDR-like RuleYesChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-002k-2129000000-90a20b25b74b231ffec1
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-06tf-4009000000-3210e4c9a7fd426e86f0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00lu-1009000000-45e9c28562c0ad9f6925
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-06to-2019000000-c4c01b7f482cdac2fc52
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0019000000-ff23a836e60f0d80784c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0098000000-e6dca75c57d753a815c3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0v03-3039000000-de1609b2f0d91b3432ed
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-204.5358815
predicted
DarkChem Lite v0.1.0
[M-H]-204.8045815
predicted
DarkChem Lite v0.1.0
[M-H]-194.27992
predicted
DeepCCS 1.0 (2019)
[M+H]+204.6103815
predicted
DarkChem Lite v0.1.0
[M+H]+204.7017815
predicted
DarkChem Lite v0.1.0
[M+H]+197.82994
predicted
DeepCCS 1.0 (2019)
[M+Na]+204.9146815
predicted
DarkChem Lite v0.1.0
[M+Na]+206.645
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
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Kind
Protein
Organism
Humans
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 an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Kim TE, Murren JR: Erlotinib OSI/Roche/Genentech. Curr Opin Investig Drugs. 2002 Sep;3(9):1385-95. [Article]
  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. [Article]
  3. Delbaldo C, Faivre S, Raymond E: [Epidermal growth factor inhibitors]. Rev Med Interne. 2003 Jun;24(6):372-83. [Article]
  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. [Article]
  5. Akita RW, Sliwkowski MX: Preclinical studies with Erlotinib (Tarceva). Semin Oncol. 2003 Jun;30(3 Suppl 7):15-24. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. 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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Erlotinib FDA label [File]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
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. [Article]
  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. [Article]
  3. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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. Vasconcelos PENS, Gergis C, Viray H, Varkaris A, Fujii M, Rangachari D, VanderLaan PA, Kobayashi IS, Kobayashi SS, Costa DB: EGFR-A763_Y764insFQEA Is a Unique Exon 20 Insertion Mutation That Displays Sensitivity to Approved and In-Development Lung Cancer EGFR Tyrosine Kinase Inhibitors. JTO Clin Res Rep. 2020 Sep;1(3). doi: 10.1016/j.jtocrr.2020.100051. Epub 2020 May 13. [Article]

Carriers

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

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
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. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [Article]
Details
2. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. 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. [Article]
  2. de Vries NA, Buckle T, Zhao J, Beijnen JH, Schellens JH, van Tellingen O: Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs. 2012 Apr;30(2):443-9. doi: 10.1007/s10637-010-9569-1. Epub 2010 Oct 21. [Article]
  3. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. doi: 10.1111/j.1349-7006.2009.01213.x. Epub 2009 May 12. [Article]
  4. Lainey E, Sebert M, Thepot S, Scoazec M, Bouteloup C, Leroy C, De Botton S, Galluzzi L, Fenaux P, Kroemer G: Erlotinib antagonizes ABC transporters in acute myeloid leukemia. Cell Cycle. 2012 Nov 1;11(21):4079-92. doi: 10.4161/cc.22382. Epub 2012 Oct 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48