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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:51:58 UTC
HMDB IDHMDB0015388
Secondary Accession Numbers
  • HMDB15388
Metabolite Identification
Common NameLapatinib
DescriptionLapatinib, also known as GW 572016 or tykerb, 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. Lapatinib is a very strong basic compound (based on its pKa). Pharmaceutical company GlaxoSmithKline (GSK) markets the drug under the propriety names Tykerb (mostly U.S.) and Tyverb (mostly Europe and Russia). It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2). Like sorafenib, lapatinib is a protein kinase inhibitor shown to decrease tumor-causing breast cancer stem cells. Phase III study designed to assess lapatinib in combination with chemotherapy for advanced HER2-positive gastric cancer in 2013 failed to meet the primary endpoint of improved overall survival (OS) against chemotherapy alone. Secondary endpoints of the randomized, double-blinded study, were progression-free survival (PFS), response rate and duration of response. The outcome of this study resulted in a somewhat complex and rather specific initial indication for lapatinib—use only in combination with capecitabine for HER2-positive breast cancer in women whose cancer have progressed following previous chemotherapy with anthracycline, taxanes and trastuzumab.
Structure
Data?1582753291
Synonyms
ValueSource
GW 572016ChEBI
N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamineChEBI
N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamineChEBI
TykerbChEBI
N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulphonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamineGenerator
N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamineGenerator
FMMHMDB
GW572016HMDB
Lapatinib ditosylateHMDB
Lapatinib tosilate hydrateHMDB
N-(3-Chloro-4-(((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-methylsulfonyl)ethyl)amino)methyl) -2-furyl)-4-quinazolinamineHMDB
Chemical FormulaC29H26ClFN4O4S
Average Molecular Weight581.058
Monoisotopic Molecular Weight580.134731942
IUPAC NameN-{3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}-6-(5-{[(2-methanesulfonylethyl)amino]methyl}furan-2-yl)quinazolin-4-amine
Traditional Namelapatinib
CAS Registry Number388082-78-8
SMILES
CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1
InChI Identifier
InChI=1S/C29H26ClFN4O4S/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)
InChI KeyBCFGMOOMADDAQU-UHFFFAOYSA-N
Chemical Taxonomy
Description 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
ClassDiazanaphthalenes
Sub ClassBenzodiazines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Phenoxy compound
  • Aniline or substituted anilines
  • Phenol ether
  • Aralkylamine
  • Halobenzene
  • Fluorobenzene
  • Chlorobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Aryl chloride
  • Heteroaromatic compound
  • Sulfonyl
  • Sulfone
  • Furan
  • Oxacycle
  • Azacycle
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.022 g/LNot Available
LogP5.4Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.022 g/LALOGPS
logP5.18ALOGPS
logP4.64ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)15.99ChemAxon
pKa (Strongest Basic)7.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area106.35 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity152.42 m³·mol⁻¹ChemAxon
Polarizability61.19 ųChemAxon
Number of Rings5ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+216.74130932474
DeepCCS[M-H]-214.34530932474
DeepCCS[M-2H]-247.38930932474
DeepCCS[M+Na]+222.65330932474
AllCCS[M+H]+233.032859911
AllCCS[M+H-H2O]+231.732859911
AllCCS[M+NH4]+234.232859911
AllCCS[M+Na]+234.532859911
AllCCS[M-H]-205.832859911
AllCCS[M+Na-2H]-206.432859911
AllCCS[M+HCOO]-207.232859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
LapatinibCS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C17155.0Standard polar33892256
LapatinibCS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C14901.5Standard non polar33892256
LapatinibCS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C15346.6Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Lapatinib,1TMS,isomer #1C[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)C3=C2)O15016.2Semi standard non polar33892256
Lapatinib,1TMS,isomer #1C[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)C3=C2)O14670.3Standard non polar33892256
Lapatinib,1TMS,isomer #1C[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)C3=C2)O16791.7Standard polar33892256
Lapatinib,1TMS,isomer #2C[Si](C)(C)N(C1=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1)C1=NC=NC2=CC=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C124749.0Semi standard non polar33892256
Lapatinib,1TMS,isomer #2C[Si](C)(C)N(C1=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1)C1=NC=NC2=CC=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C124594.4Standard non polar33892256
Lapatinib,1TMS,isomer #2C[Si](C)(C)N(C1=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1)C1=NC=NC2=CC=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C126584.8Standard polar33892256
Lapatinib,2TMS,isomer #1C[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(N(C4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)[Si](C)(C)C)C3=C2)O14735.9Semi standard non polar33892256
Lapatinib,2TMS,isomer #1C[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(N(C4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)[Si](C)(C)C)C3=C2)O14809.5Standard non polar33892256
Lapatinib,2TMS,isomer #1C[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(N(C4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)[Si](C)(C)C)C3=C2)O16089.0Standard polar33892256
Lapatinib,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)C3=C2)O15229.2Semi standard non polar33892256
Lapatinib,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)C3=C2)O14929.4Standard non polar33892256
Lapatinib,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)C3=C2)O16707.0Standard polar33892256
Lapatinib,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N(C1=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1)C1=NC=NC2=CC=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C124989.0Semi standard non polar33892256
Lapatinib,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N(C1=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1)C1=NC=NC2=CC=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C124827.1Standard non polar33892256
Lapatinib,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N(C1=CC=C(OCC2=CC=CC(F)=C2)C(Cl)=C1)C1=NC=NC2=CC=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C126460.6Standard polar33892256
Lapatinib,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(N(C4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)[Si](C)(C)C(C)(C)C)C3=C2)O15150.7Semi standard non polar33892256
Lapatinib,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(N(C4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)[Si](C)(C)C(C)(C)C)C3=C2)O15266.3Standard non polar33892256
Lapatinib,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CCS(C)(=O)=O)CC1=CC=C(C2=CC=C3N=CN=C(N(C4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)[Si](C)(C)C(C)(C)C)C3=C2)O15994.6Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Lapatinib GC-MS (Non-derivatized) - 70eV, Positivesplash10-0pb9-6920550000-7316e856fd5ec8e04f072017-09-01Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib LC-ESI-qTof , Positive-QTOFsplash10-00lr-0009070000-0d55ba750eaa2fb120202017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib , positive-QTOFsplash10-00lr-0009070000-0d55ba750eaa2fb120202017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib , positive-QTOFsplash10-0ab9-0649800000-87742edfe3489dab4ac82017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib 30V, Positive-QTOFsplash10-001i-0002090000-49e599088394c442e60b2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib 40V, Positive-QTOFsplash10-014i-0009020000-1e12983abcdd66482af32021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib 10V, Positive-QTOFsplash10-001i-0000090000-f080a7f403cbfd88c5902021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib 20V, Positive-QTOFsplash10-001i-0000090000-e1a1377443b8f411d9972021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib 50V, Positive-QTOFsplash10-014i-0009000000-0b1867dee117396c19492021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Lapatinib 10V, Positive-QTOFsplash10-001i-0000090000-d725217276a0f9a7e7932021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 10V, Positive-QTOFsplash10-001i-0100290000-631c05424fb5cef349db2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 20V, Positive-QTOFsplash10-0a5i-1701890000-169201e0014b0f4031fc2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 40V, Positive-QTOFsplash10-0a4i-6922200000-21ac033aa8e06fb42b192016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 10V, Negative-QTOFsplash10-004i-5100190000-854bae0cfc77e5929d1e2016-08-04Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 20V, Negative-QTOFsplash10-004i-9100110000-7b6eac51a2b17a8a02132016-08-04Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 40V, Negative-QTOFsplash10-004i-9100000000-16d9d0819f6dca47cd5c2016-08-04Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 10V, Positive-QTOFsplash10-001i-0000290000-c15d2a8b4702b6befdbd2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 20V, Positive-QTOFsplash10-001i-0001490000-80635a463a3e3328f17b2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 40V, Positive-QTOFsplash10-0pbj-2119400000-10638e7b757119205a692021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 10V, Negative-QTOFsplash10-004i-0000090000-9043926cc3ed698dc68e2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 20V, Negative-QTOFsplash10-03fr-1109630000-a046bbec44d7c31559d02021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Lapatinib 40V, Negative-QTOFsplash10-0059-9204010000-e84077eb1512ec5949ba2021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01259 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01259 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01259
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID181006
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLapatinib
METLIN IDNot Available
PubChem Compound208908
PDB IDNot Available
ChEBI ID49603
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Burris HA 3rd: Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib. Oncologist. 2004;9 Suppl 3:10-5. [PubMed:15163842 ]
  2. Johnston SR, Leary A: Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today (Barc). 2006 Jul;42(7):441-53. [PubMed:16894399 ]
  3. Tevaarwerk AJ, Kolesar JM: Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer. Clin Ther. 2009;31 Pt 2:2332-48. doi: 10.1016/j.clinthera.2009.11.029. [PubMed:20110044 ]
  4. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  5. Burris HA 3rd, Hurwitz HI, Dees EC, Dowlati A, Blackwell KL, O'Neil B, Marcom PK, Ellis MJ, Overmoyer B, Jones SF, Harris JL, Smith DA, Koch KM, Stead A, Mangum S, Spector NL: Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol. 2005 Aug 10;23(23):5305-13. Epub 2005 Jun 13. [PubMed:15955900 ]
  6. Nelson MH, Dolder CR: Lapatinib: a novel dual tyrosine kinase inhibitor with activity in solid tumors. Ann Pharmacother. 2006 Feb;40(2):261-9. Epub 2006 Jan 17. [PubMed:16418322 ]
  7. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. [PubMed:17192538 ]

Enzymes

General function:
Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  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 ]
  3. Teng WC, Oh JW, New LS, Wahlin MD, Nelson SD, Ho HK, Chan EC: Mechanism-based inactivation of cytochrome P450 3A4 by lapatinib. Mol Pharmacol. 2010 Oct;78(4):693-703. doi: 10.1124/mol.110.065839. Epub 2010 Jul 12. [PubMed:20624855 ]
General function:
Involved in monooxygenase 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:
55944.565
References
  1. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  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 ]
General function:
Involved in transmembrane receptor protein tyrosine kinase activity
Specific function:
Isoform 2 may act as an antagonist of EGF action
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular weight:
134276.2
References
  1. Xia W, Mullin RJ, Keith BR, Liu LH, Ma H, Rusnak DW, Owens G, Alligood KJ, Spector NL: Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene. 2002 Sep 12;21(41):6255-63. [PubMed:12214266 ]
  2. Grana TM, Sartor CI, Cox AD: Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed by the Ras oncogene enhances radiation resistance. Cancer Res. 2003 Nov 15;63(22):7807-14. [PubMed:14633707 ]
  3. Xia W, Liu LH, Ho P, Spector NL: Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene. 2004 Jan 22;23(3):646-53. [PubMed:14737100 ]
  4. Zhou H, Kim YS, Peletier A, McCall W, Earp HS, Sartor CI: Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance. Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):344-52. [PubMed:14751502 ]
  5. Langer CJ: Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):991-1002. [PubMed:14967461 ]
  6. Burris HA 3rd: Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib. Oncologist. 2004;9 Suppl 3:10-5. [PubMed:15163842 ]
  7. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C, Horne E, Lackey K, Alligood KJ, Rusnak DW, Gilmer TM, Shewchuk L: A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 2004 Sep 15;64(18):6652-9. [PubMed:15374980 ]
  8. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA: Lapatinib, a dual HER1/HER2 tyrosine kinase inhibitor, augments basal cleavage of HER2 extracellular domain (ECD) to inhibit HER2-driven cancer cell growth. J Cell Physiol. 2011 Jan;226(1):52-7. doi: 10.1002/jcp.22333. [PubMed:20658522 ]
  9. Johnston SR, Leary A: Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today (Barc). 2006 Jul;42(7):441-53. [PubMed:16894399 ]
  10. Tevaarwerk AJ, Kolesar JM: Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer. Clin Ther. 2009;31 Pt 2:2332-48. doi: 10.1016/j.clinthera.2009.11.029. [PubMed:20110044 ]
  11. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in transmembrane receptor protein tyrosine kinase activity
Specific function:
Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Binds to the 5'-TCAAATTC-3' sequence in the MT-CO2 promoter and activates its transcription
Gene Name:
ERBB2
Uniprot ID:
P04626
Molecular weight:
137909.3
References
  1. Xia W, Liu LH, Ho P, Spector NL: Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene. 2004 Jan 22;23(3):646-53. [PubMed:14737100 ]
  2. Zhou H, Kim YS, Peletier A, McCall W, Earp HS, Sartor CI: Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance. Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):344-52. [PubMed:14751502 ]
  3. Langer CJ: Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):991-1002. [PubMed:14967461 ]
  4. Burris HA 3rd: Dual kinase inhibition in the treatment of breast cancer: initial experience with the EGFR/ErbB-2 inhibitor lapatinib. Oncologist. 2004;9 Suppl 3:10-5. [PubMed:15163842 ]
  5. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C, Horne E, Lackey K, Alligood KJ, Rusnak DW, Gilmer TM, Shewchuk L: A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 2004 Sep 15;64(18):6652-9. [PubMed:15374980 ]
  6. Grana TM, Sartor CI, Cox AD: Epidermal growth factor receptor autocrine signaling in RIE-1 cells transformed by the Ras oncogene enhances radiation resistance. Cancer Res. 2003 Nov 15;63(22):7807-14. [PubMed:14633707 ]
  7. Xia W, Mullin RJ, Keith BR, Liu LH, Ma H, Rusnak DW, Owens G, Alligood KJ, Spector NL: Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene. 2002 Sep 12;21(41):6255-63. [PubMed:12214266 ]
  8. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA: Lapatinib, a dual HER1/HER2 tyrosine kinase inhibitor, augments basal cleavage of HER2 extracellular domain (ECD) to inhibit HER2-driven cancer cell growth. J Cell Physiol. 2011 Jan;226(1):52-7. doi: 10.1002/jcp.22333. [PubMed:20658522 ]
  9. Johnston SR, Leary A: Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today (Barc). 2006 Jul;42(7):441-53. [PubMed:16894399 ]
  10. Tevaarwerk AJ, Kolesar JM: Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer. Clin Ther. 2009;31 Pt 2:2332-48. doi: 10.1016/j.clinthera.2009.11.029. [PubMed:20110044 ]
  11. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in monooxygenase 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:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
References
  1. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  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 ]
General function:
Involved in monooxygenase 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 responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
References
  1. Medina PJ, Goodin S: Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008 Aug;30(8):1426-47. doi: 10.1016/j.clinthera.2008.08.008. [PubMed:18803986 ]
  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 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Dai CL, Tiwari AK, Wu CP, Su XD, Wang SR, Liu DG, Ashby CR Jr, Huang Y, Robey RW, Liang YJ, Chen LM, Shi CJ, Ambudkar SV, Chen ZS, Fu LW: Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer Res. 2008 Oct 1;68(19):7905-14. doi: 10.1158/0008-5472.CAN-08-0499. [PubMed:18829547 ]
General function:
Involved in ATP binding
Specific function:
Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules
Gene Name:
TAP1
Uniprot ID:
Q03518
Molecular weight:
87216.9
References
  1. Dai CL, Tiwari AK, Wu CP, Su XD, Wang SR, Liu DG, Ashby CR Jr, Huang Y, Robey RW, Liang YJ, Chen LM, Shi CJ, Ambudkar SV, Chen ZS, Fu LW: Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer Res. 2008 Oct 1;68(19):7905-14. doi: 10.1158/0008-5472.CAN-08-0499. [PubMed:18829547 ]