Identification

Name
Lapatinib
Accession Number
DB01259  (DB02584)
Type
Small Molecule
Groups
Approved, Investigational
Description

Lapatinib is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug Capecitabine. Lapatinib is human epidermal growth factor receptor type 2 (HER2/ERBB2) and epidermal growth factor receptor (HER1/EGFR/ERBB1) tyrosine kinases inhibitor. It binds to the intracellular phosphorylation domain to prevent receptor autophosphorylation upon ligand binding.

Structure
Thumb
Synonyms
  • FMM
  • GW 572016
  • Lapatinib
  • Lapatinib tosilate hydrate
  • N-(3-chloro-4-((3-Fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamine
  • N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine
External IDs
GW 572016 / GW572016
Product Ingredients
IngredientUNIICASInChI Key
Lapatinib ditosylateG873GX646R388082-78-8XNRVGTHNYCNCFF-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TykerbTablet250 mgOralNovartis2009-06-05Not applicableCanada
TykerbTablet250 mg/1OralGlaxosmithkline Inc2007-03-162017-11-30Us00173 0752 00 nlmimage10 8318c1b6
TykerbTablet250 mg/1OralNovartis Pharmaceuticals Corporation2016-08-03Not applicableUs
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
TyverbTablet, film coated250 mgOralNovartis Europharm Limited2008-06-10Not applicableEu
International/Other Brands
Tycerb / Tykerb
Categories
UNII
0VUA21238F
CAS number
231277-92-2
Weight
Average: 581.058
Monoisotopic: 580.134731942
Chemical Formula
C29H26ClFN4O4S
InChI Key
BCFGMOOMADDAQU-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-{3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}-6-(5-{[(2-methanesulfonylethyl)amino]methyl}furan-2-yl)quinazolin-4-amine
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

Pharmacology

Indication

Indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress the human epidermal receptor type 2 (HER2) protein and who have received prior therapy including an anthracycline, a taxane, and trastuzuma.

Associated Conditions
Pharmacodynamics

Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. An anti-cancer drug, lapatinib was developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine.

Mechanism of action

Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both epidermal growth factor receptor (HER1/EGFR/ERBB1) and human epidermal growth factor receptor type 2 (HER2/ERBB2)with a dissociation half-life of ≥300 minutes. Lapatinib inhibits ERBB-driven tumor cell growth in vitro and in various animal models. An additive effect was demonstrated in an in vitro study when lapatinib and 5-florouracil (the active metabolite of capecitabine) were used in combination in the 4 tumor cell lines tested. The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines. Lapatinib retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro. These in vitro findings suggest non-cross-resistance between these two agents.

TargetActionsOrganism
AEpidermal growth factor receptor
antagonist
Human
AReceptor tyrosine-protein kinase erbB-2
antagonist
Human
Absorption

Absorption following oral administration of lapatinib is incomplete and variable.

Volume of distribution
Not Available
Protein binding

Highly bound (>99%) to albumin and alpha-1 acid glycoprotein

Metabolism

Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which accounts for more than 14% of the dose recovered in the feces or 10% of lapatinib concentration in plasma.

Route of elimination

Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which accounts for more than 14% of the dose recovered in the feces or 10% of lapatinib concentration in plasma.

Half life

Single-dose terminal half life: 14.2 hours Effective multiple-dose half life: 24 hours

Clearance
Not Available
Toxicity

There has been a report of one patient who took 3,000 mg of lapatinib for 10 days. This patient had grade 3 diarrhea and vomiting on day 10.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
HLA class II histocompatibility antigen, DQ alpha 1 chainHLA-DQA1*02:01Not AvailableHLA-DQA1*02ADR Directly StudiedThe presence of this polymorphism in TNXB may indicate an increased risk of drug-induced ALT-elevations leading to hepatotoxicity when treated with lapatinib.Details
HLA class II histocompatibility antigen, DRB1-11 beta chainHLA-DRB1*07:01Not AvailableHLA-DRB1*07ADR Directly StudiedThe presence of this polymorphism in TNXB may indicate an increased risk of drug-induced ALT-elevations leading to hepatotoxicity when treated with lapatinib.Details
HLA class II histocompatibility antigen, DQ beta 1 chainHLA-DQB1*02:02Not AvailableHLA-DQB1*02ADR Directly StudiedThe presence of this polymorphism in TNXB may indicate an increased risk of drug-induced ALT-elevations leading to hepatotoxicity when treated with lapatinib.Details
Tenascin-X---(C;C) / (C;T)T > CADR Directly StudiedThe presence of this polymorphism in TNXB may indicate an increased risk of drug-induced ALT-elevations leading to hepatotoxicity when treated with lapatinib.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lapatinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lapatinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lapatinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lapatinib.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Lapatinib.
6-Deoxyerythronolide BThe metabolism of Lapatinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Lapatinib.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Lapatinib.
AbataceptThe metabolism of Lapatinib can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Lapatinib.
Food Interactions
Not Available

References

Synthesis Reference
US6727256
General References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
External Links
Human Metabolome Database
HMDB0015388
KEGG Drug
D04024
PubChem Compound
208908
PubChem Substance
46507141
ChemSpider
181006
BindingDB
5445
ChEBI
49603
ChEMBL
CHEMBL554
Therapeutic Targets Database
DCL000344
PharmGKB
PA152241907
HET
FMM
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lapatinib
ATC Codes
L01XE07 — Lapatinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1xkk / 3bbt

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingDiagnosticNeoplasms, Breast1
0Active Not RecruitingTreatmentCancer, Breast1
0TerminatedNot AvailableBladder Carcinoma / Cystectomy / Infiltrative Bladder Carcinoma1
0TerminatedTreatmentEpithelial Cancer1
0Unknown StatusBasic ScienceAcoustic Schwannoma / Auditory Tumor / Neurofibromatosis 2 / NF2 / Vestibular Schwannomas1
1Active Not RecruitingTreatmentBRAF V600E Mutation Present / BRAF V600K Mutation Present / Metastatic Malignant Neoplasm in the Thyroid Gland / Metastatic Thyroid Gland Carcinoma / Recurrent Thyroid Gland Carcinoma / Unresectable Thyroid Gland Carcinoma1
1Active Not RecruitingTreatmentCancer, Advanced1
1Active Not RecruitingTreatmentHER2/Neu Positive / Invasive Breast Carcinoma / Recurrent Breast Carcinoma / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v71
1Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)2
1Active Not RecruitingTreatmentNeoplasms, Breast2
1CompletedOtherAdvanced or Metastatic ErbB2-overexpressing Breast Cancer / Neoplasms, Breast1
1CompletedOtherMalignancies1
1CompletedTreatmentAdvanced Cancers2
1CompletedTreatmentAdvanced Colorectal Cancer / Metastatic Colorectal Cancers / Neoplasms, Colorectal / Responsive to Fluoropyrimidines1
1CompletedTreatmentAdvanced Non-Small Cell Lung Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentAdvanced or Metastatic ErbB2-overexpressing Breast Cancer / Neoplasms, Breast1
1CompletedTreatmentAnemia of Chronic Kidney Disease1
1CompletedTreatmentBladder Cancers / Brain and Central Nervous System Tumors / Cancer of the Ovary / Cancer, Breast / Esophageal Cancers / Extragonadal Germ Cell Tumor / Lung Cancers / Malignant Neoplasm of Stomach / Prostate Cancer1
1CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter1
1CompletedTreatmentCancer, Breast7
1CompletedTreatmentCancer, Breast / Locally Recurrent and Metastatic Breast Cancer / Malignancies / Metastases / Metastatic Cancers / Neoplasms, Breast / Oncology / Tumors / Tumors, Breast / Tumors, Solid1
1CompletedTreatmentCancer, Breast / Metastatic Brain Tumors1
1CompletedTreatmentCancer, Breast / Metastatic Cancers1
1CompletedTreatmentCancer, Breast / Metastatic ErbB2 / Neoplasms, Breast1
1CompletedTreatmentCancer, Breast / Neoplasms, Breast1
1CompletedTreatmentColorectal Cancers / Head and Neck Carcinoma / Lung Cancers1
1CompletedTreatmentHER-2 Gene Amplification1
1CompletedTreatmentHER2 Positive / Metastatic Brain Tumors / Metastatic Breast Cancer (MBC)1
1CompletedTreatmentHer2-Positive Breast Cancer / Male Breast Cancer / Recurrent Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentLocally Advanced Breast Cancer (LABC) / Metastatic Breast Cancer (MBC)1
1CompletedTreatmentMalignancies / Neoplasms, Breast2
1CompletedTreatmentMalignancies / Renal Cell Adenocarcinoma1
1CompletedTreatmentMalignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentNeoplasms, Breast4
1CompletedTreatmentNeoplasms, Breast / Solid Tumor Cancers2
1CompletedTreatmentRenal Cell Adenocarcinoma1
1CompletedTreatmentTumors, Solid2
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific2
1RecruitingTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Ependymoma / Adult Anaplastic Oligodendroglioma / Adult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Adult Mixed Glioma / Anaplastic Astrocytoma (AA) / Anaplastic Ependymoma / Anaplastic Oligodendroglioma (AO) / Gliosarcoma / Mixed Gliomas / Recurrent Adult Brain Neoplasm / Recurrent Glioblastoma1
1TerminatedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Advanced Gastric Cancer / Her2-Positive Breast Cancer / Male Breast Cancer / Recurrent Breast Cancer / Recurrent Esophageal Cancer / Recurrent Gastric Cancer / Stage IIIC Breast Cancer / Stage IIIC Esophageal Cancer / Stage IIIC Gastric Cancer / Stage IV Breast Cancer / Stage IV Esophageal Cancer1
1TerminatedTreatmentAdvanced Solid Tumors1
1TerminatedTreatmentAdvanced Solid Tumors / Cancer, Breast1
1TerminatedTreatmentCancer of the Ovary1
1TerminatedTreatmentEstrogen Receptor Negative / Estrogen Receptor Positive / HER2/Neu Positive / Progesterone Receptor Negative / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IV Breast Cancer1
1TerminatedTreatmentFailure or Contraindication of Trastuzumab Therapy / First or Second Line Therapy / HER2 Positive / Metastatic Breast Cancer (MBC)1
1TerminatedTreatmentHER-2 Positive Breast Cancer / Malignant Neoplasm of Breast1
1TerminatedTreatmentLocally Advanced or Metastatic Breast Cancer1
1TerminatedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1Unknown StatusTreatmentCancer, Breast1
1Unknown StatusTreatmentRecurrent Endometrial Cancer1
1WithdrawnNot AvailableCancer, Breast1
1WithdrawnTreatmentHealthy Volunteers1
1, 2Active Not RecruitingTreatmentCentral Nervous System Metastases / Her2-Positive Breast Cancer / Male Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
1, 2Active Not RecruitingTreatmentHER2 Positive Metastatic Breast Cancers1
1, 2CompletedNot AvailableMetastatic Breast Cancer (MBC)1
1, 2CompletedTreatmentBrain and Central Nervous System Tumors1
1, 2CompletedTreatmentCancer, Breast4
1, 2CompletedTreatmentHead and Neck Carcinoma1
1, 2CompletedTreatmentMetastatic Breast Cancer (MBC)1
1, 2CompletedTreatmentOvarian Epithelial Cancer Stage III / Stage IV Breast Cancer / Stage IV Ovarian Cancer1
1, 2CompletedTreatmentRecurrent Childhood Anaplastic Astrocytoma / Recurrent Childhood Brain Stem Glioma / Recurrent Childhood Ependymoma / Recurrent Childhood Giant Cell Glioblastoma / Recurrent Childhood Glioblastoma / Recurrent Childhood Gliosarcoma / Recurrent Childhood Medulloblastoma / Recurrent Childhood Oligodendroglioma1
1, 2RecruitingTreatmentColorectal Cancers1
1, 2SuspendedTreatmentCancer, Breast1
1, 2TerminatedTreatmentAdenocarcinoma of the Esophagus / Adenocarcinomas of the Gastroesophageal Junction1
1, 2TerminatedTreatmentCancer, Breast / Neoplasms Metastasis1
1, 2TerminatedTreatmentHER2 Positive Metastatic Breast Cancers1
1, 2TerminatedTreatmentMetastatic Breast Cancer (MBC)1
1, 2TerminatedTreatmentProstate Cancer1
1, 2Unknown StatusTreatmentMetastatic Breast Cancer (MBC)1
2Active Not RecruitingTreatmentCancer, Breast4
2Active Not RecruitingTreatmentGeriatric Health Services / HER2/Neu Positive / Neoplasms, Breast1
2Active Not RecruitingTreatmentHER2-Positive Early Stage Breast Cancer1
2Active Not RecruitingTreatmentHER2/Neu Positive / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v7 / Stage IIIC Breast Cancer / Stage IIIC Breast Cancer AJCC v7 / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v71
2Active Not RecruitingTreatmentHead and Neck Carcinoma / Squamous Cell Carcinoma (SCC)1
2Active Not RecruitingTreatmentHead and Neck Carcinoma / Squamous Cell Carcinoma of the Head and Neck (SCCHN)1
2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2Active Not RecruitingTreatmentMetastatic Breast Cancer With Intracranial Metastases1
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
2Active Not RecruitingTreatmentNeoplasms, Breast2
2Active Not RecruitingTreatmentNon-HPV Locally Advanced Head and Neck Cancer1
2CompletedTreatment70 Years Old Patients and Over / After One Line of Chemotherapy With Trastuzumab / Metastatic Breast Cancer (MBC)1
2CompletedTreatmentAdenocarcinomas1
2CompletedTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer / Recurrent Extrahepatic Bile Duct Cancer / Recurrent Gallbladder Cancer / Unresectable Extrahepatic Bile Duct Cancer / Unresectable Gallbladder Cancer2
2CompletedTreatmentAdvanced Breast Cancer / Cancer, Breast1
2CompletedTreatmentAdvanced Gastric Cancer / Diffuse Adenocarcinoma of the Stomach / Intestinal Adenocarcinoma of the Stomach / Mixed Adenocarcinoma of the Stomach / Recurrent Gastric Cancer / Stage III Gastric Cancer1
2CompletedTreatmentBrain Cancer / Pediatric Cancers1
2CompletedTreatmentCancer of the Ovary / Peritoneal Cavity Cancer1
2CompletedTreatmentCancer, Breast10
2CompletedTreatmentCancer, Breast / Cardiac Toxicity1
2CompletedTreatmentCancer, Breast / ErbB1 Expressing / ErbB2 Overexpressing / Inflammatory / Neoplasms, Breast / Newly Diagnosed1
2CompletedTreatmentCancer, Breast / Metastatic Breast Cancer (MBC)1
2CompletedTreatmentCancer, Breast / Metastatic Cancers1
2CompletedTreatmentCentral Nervous System Metastases / Her2-Positive Breast Cancer / Male Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer / Tumors Metastatic to Brain1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEstrogen Receptor Positive / Male Breast Carcinoma / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentGBM / Glioblastoma Multiforme (GBM) / Gliomas / Gliosarcoma / GS / Neoplasms, Brain1
2CompletedTreatmentGliomas1
2CompletedTreatmentHER2-positive Gastric Cancer Patients With Liver Metastasis1
2CompletedTreatmentHER2-positive Refractory Advanced Cancer1
2CompletedTreatmentHead and Neck Carcinoma / Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Salivary Gland Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Verrucous Carcinoma of the Larynx / Recurrent Verrucous Carcinoma of the Oral Cavity / Salivary Gland Squamous Cell Carcinoma / Stage IV Salivary Gland Cancer / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Oropharynx / Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IV Verrucous Carcinoma of the Larynx / Stage IV Verrucous Carcinoma of the Oral Cavity1
2CompletedTreatmentHer2-Positive Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer1
2CompletedTreatmentHigh-grade Salivary Gland Carcinoma / High-grade Salivary Gland Mucoepidermoid Carcinoma / Low-grade Salivary Gland Carcinoma / Low-grade Salivary Gland Mucoepidermoid Carcinoma / Recurrent Adenoid Cystic Carcinoma of the Oral Cavity / Recurrent Salivary Gland Cancer / Salivary Gland Acinic Cell Tumor / Salivary Gland Adenocarcinoma / Salivary Gland Adenoid Cystic Carcinoma / Salivary Gland Malignant Mixed Cell Type Tumor1
2CompletedTreatmentLung Tumors / Metastatic Brain Tumors / Tumors, Breast1
2CompletedTreatmentMalignancies2
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2CompletedTreatmentMetastatic Breast Cancer (MBC)2
2CompletedTreatmentMetastatic Breast Cancer (MBC) / Neoplasms, Breast1
2CompletedTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentMetastatic Squamous Neck Cancer With Occult Primary / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Salivary Gland Squamous Cell Carcinoma / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IV Squamous Cell Carcinoma of the Oropharynx / Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Untreated Metastatic Squamous Neck Cancer With Occult Primary1
2CompletedTreatmentNeoplasms, Brain / Spinal Cord Tumors1
2CompletedTreatmentNeoplasms, Breast13
2CompletedTreatmentNeoplasms, Gastrointestinal Tract1
2CompletedTreatmentNeoplasms, Head and Neck1
2CompletedTreatmentNeoplasms, Uterine Cervix / Recurrent, IV-B Cervical cancer1
2CompletedTreatmentNeurofibromatosis 2 / Vestibular Schwannomas1
2CompletedTreatmentPrimary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Endometrial Carcinoma1
2CompletedTreatmentRecurrent Prostate Cancer / Stage I Prostate Cancer / Stage IIA Prostate Cancer / Stage IIB Prostate Cancer / Stage III Prostate Cancer1
2CompletedTreatmentRecurrent Prostate Cancer / Stage IV Prostate Cancer1
2CompletedTreatmentRecurrent Salivary Gland Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Verrucous Carcinoma of the Larynx / Recurrent Verrucous Carcinoma of the Oral Cavity / Salivary Gland Squamous Cell Carcinoma / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IVA Salivary Gland Cancer / Stage IVA Squamous Cell Carcinoma of the Larynx / Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVA Squamous Cell Carcinoma of the Oropharynx / Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVA Verrucous Carcinoma of the Larynx / Stage IVA Verrucous Carcinoma of the Oral Cavity / Stage IVB Salivary Gland Cancer / Stage IVB Squamous Cell Carcinoma of the Larynx / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Oropharynx / Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVB Verrucous Carcinoma of the Larynx / Stage IVB Verrucous Carcinoma of the Oral Cavity / Stage IVC Salivary Gland Cancer / Stage IVC Squamous Cell Carcinoma of the Larynx / Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVC Squamous Cell Carcinoma of the Oropharynx / Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVC Verrucous Carcinoma of the Larynx / Stage IVC Verrucous Carcinoma of the Oral Cavity / Tongue Cancer1
2CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2RecruitingTreatmentBreast Diseases / Capecitabine / HER2 Positive Breast Carcinoma / Her2-Positive Breast Cancer / Neoplasms, Breast1
2RecruitingTreatmentCarcinoma, Ductal, Breast1
2RecruitingTreatmentCholangiocarcinoma of the Extrahepatic Bile Duct / Gallbladder Cancer1
2RecruitingTreatmentERBB2 Gene Amplification / HER2 Positive Breast Carcinoma / HER2/Neu Positive / Invasive Breast Carcinoma / Male Breast Carcinoma / Metastatic Malignant Neoplasm in the Brain / Recurrent Breast Carcinoma / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v71
2RecruitingTreatmentHER2 Positive Breast Cancers1
2RecruitingTreatmentHer2-Positive Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Small Cell Lung Carcinoma / Thymic Carcinoma1
2RecruitingTreatmentMalignant Solid Neoplasms1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)2
2RecruitingTreatmentNeoplasms, Breast1
2RecruitingTreatmentNeuroblastomas1
2RecruitingTreatmentPituitary Adenomas / Prolactinomas1
2TerminatedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Malignant Neoplasm of Stomach1
2TerminatedTreatmentAdvanced Breast Cancer / Cancer, Breast / HER2/Neu-positive Breast Cancer / Metastatic Breast Cancer (MBC)1
2TerminatedTreatmentCancer of the Breast / Cancer, Breast / Neoplasms, Breast1
2TerminatedTreatmentCancer, Breast4
2TerminatedTreatmentEndocrine Breast Diseases / Neoplasms Metastasis / Neoplasms, Breast1
2TerminatedTreatmentGastrooesophageal Cancer1
2TerminatedTreatmentHER2 Positive Esophagogastric Cancer1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2TerminatedTreatmentMalignancies2
2TerminatedTreatmentCancer treatment / Malignancies / Ovarian / Relapses1
2TerminatedTreatmentMalignant Melanoma1
2TerminatedTreatmentMalignant Neoplasm of Pancreas1
2TerminatedTreatmentMetastatic Bladder Cancer / Recurrent Bladder Cancer / Stage III Bladder Cancer / Transitional Cell Carcinoma of the Bladder1
2TerminatedTreatmentMetastatic Breast Cancer (MBC)4
2TerminatedTreatmentMetastatic or Recurrent Squamous Cell Carcinoma of the Esophagus1
2TerminatedTreatmentNeoplasms, Breast3
2TerminatedTreatmentNeoplasms, Breast / Relapsed Breast Cancer1
2TerminatedTreatmentPancreatic Cancer Metastatic1
2TerminatedTreatmentSquamous Cell Carcinoma (SCC)1
2Unknown StatusTreatmentErbB2-Positive Stage I-III Breast Cancer1
2Unknown StatusTreatmentMetastatic Breast Cancer (MBC)1
2WithdrawnTreatmentBladder Cancers / Urothelial Cancer1
2WithdrawnTreatmentCancer, Breast2
2WithdrawnTreatmentNeoplasms, Breast3
2, 3Active Not RecruitingTreatmentBladder Cancers1
2, 3CompletedTreatmentCancer, Breast1
2, 3CompletedTreatmentHER-2 Positive Breast Cancer / Inflammatory carcinoma of breast stage IV / Inflammatory carcinoma of the breast / Invasive Ductal Breast Carcinoma / Malignant Neoplasm of Female Breast / Mucinous Breast Cancer Stage II / Tubular Breast Cancer Stage II / Tubular Breast Cancer Stage III1
2, 3RecruitingTreatmentHer2-Positive Breast Cancer1
2, 3RecruitingTreatmentOesophagogastric Cancer1
3Active Not RecruitingTreatmentBreast Cancer Invasive Nos1
3Active Not RecruitingTreatmentCancer, Breast3
3Active Not RecruitingTreatmentEstrogen Receptor Positive / HER2 Positive Breast Carcinoma / HER2/Neu Negative / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v7 / Stage IIIC Breast Cancer / Stage IIIC Breast Cancer AJCC v7 / Stage IV Breast Cancer / Stage IV Breast Cancer AJCC v6 and v71
3Active Not RecruitingTreatmentHER2+ Metastatic Breast Cancer (MBC)1
3Active Not RecruitingTreatmentHER2/Neu Positive / Male Breast Carcinoma / Stage IIA Breast Cancer / Stage IIA Breast Cancer AJCC v6 and v7 / Stage IIB Breast Cancer / Stage IIB Breast Cancer AJCC v6 and v7 / Stage IIIA Breast Cancer / Stage IIIA Breast Cancer AJCC v7 / Stage IIIB Breast Cancer / Stage IIIB Breast Cancer AJCC v7 / Stage IIIC Breast Cancer / Stage IIIC Breast Cancer AJCC v71
3Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3Active Not RecruitingTreatmentNeoplasms, Breast5
3Active Not RecruitingTreatmentNeoplasms, Gastrointestinal Tract1
3CompletedTreatmentCancer, Breast2
3CompletedTreatmentMalignancies1
3CompletedTreatmentMetastatic Brain Tumors1
3CompletedTreatmentNeoplasms, Breast4
3CompletedTreatmentNeoplasms, Gastrointestinal Tract1
3CompletedTreatmentNeoplasms, Head and Neck1
3RecruitingTreatmentCancer, Breast1
3RecruitingTreatmentHer2-negative Metastatic Breast Cancer / HER2-positive Circulating Tumor Cells1
3RecruitingTreatmentMetastatic Breast Cancer (MBC)2
3Unknown StatusTreatmentCancer, Breast1
4Approved for MarketingNot AvailableNeoplasms, Breast1
4CompletedTreatmentMalignancies1
Not AvailableActive Not RecruitingDiagnosticAdvanced Solid Tumors / Malignancies1
Not AvailableActive Not RecruitingTreatmentMetastatic Triple Negative Breast Cancer1
Not AvailableCompletedNot AvailableCancer, Breast / Metastatic Cancers1
Not AvailableCompletedNot AvailableMalignancies2
Not AvailableCompletedTreatmentDuctal Breast Carcinoma In Situ / Her2-Positive Breast Cancer / HER2/Neu Positive1
Not AvailableTerminatedBasic ScienceDuctal Carcinoma In Situ1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • GlaxoSmithKline Inc.
Dosage forms
FormRouteStrength
TabletOral250 mg
TabletOral250 mg/1
Tablet, film coatedOral250 mg
Prices
Unit descriptionCostUnit
Tykerb 250 mg tablet28.4USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2413134No2010-05-112021-06-28Canada
CA2317589No2007-08-082019-01-08Canada
US6391874No2002-05-212017-07-11Us
US6713485No2004-03-302020-09-29Us
US6727256No2004-04-272019-01-08Us
US6828320No2004-12-072017-07-11Us
US8821927No2014-09-022029-09-18Us
US8513262No2013-08-202019-01-08Us
US7157466No2007-01-022021-11-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP5.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0223 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity152.42 m3·mol-1ChemAxon
Polarizability61.19 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.6201
Caco-2 permeable-0.5858
P-glycoprotein substrateSubstrate0.7403
P-glycoprotein inhibitor IInhibitor0.5414
P-glycoprotein inhibitor IINon-inhibitor0.7799
Renal organic cation transporterNon-inhibitor0.7442
CYP450 2C9 substrateNon-substrate0.6688
CYP450 2D6 substrateNon-substrate0.7644
CYP450 3A4 substrateSubstrate0.6619
CYP450 1A2 substrateInhibitor0.5386
CYP450 2C9 inhibitorNon-inhibitor0.5544
CYP450 2D6 inhibitorNon-inhibitor0.7861
CYP450 2C19 inhibitorInhibitor0.5274
CYP450 3A4 inhibitorInhibitor0.8065
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9104
Ames testNon AMES toxic0.543
CarcinogenicityNon-carcinogens0.6788
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5867 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.537
hERG inhibition (predictor II)Inhibitor0.8417
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lr-0009070000-0d55ba750eaa2fb12020
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ab9-0649800000-87742edfe3489dab4ac8

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolinamines
Alternative Parents
Phenoxy compounds / Phenol ethers / Aniline and substituted anilines / Alkyl aryl ethers / Aminopyrimidines and derivatives / Aralkylamines / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides
show 12 more
Substituents
Quinazolinamine / Phenol ether / Phenoxy compound / Aniline or substituted anilines / Halobenzene / Alkyl aryl ether / Aminopyrimidine / Fluorobenzene / Aralkylamine / Chlorobenzene
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, organochlorine compound, furans, quinazolines (CHEBI:49603)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Transmembrane signaling receptor activity
Specific Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, alt...
Gene Name
ERBB2
Uniprot ID
P04626
Uniprot Name
Receptor tyrosine-protein kinase erbB-2
Molecular Weight
137909.27 Da
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]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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]
  4. Tykerb (Lapatinib) FDA Label [Link]
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. Tykerb (Lapatinib) FDA Label [Link]
Kind
Protein
Organism
Human
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. 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]
  2. Get to know an Enzyme: CYP2C8 [Link]
  3. Tykerb (Lapatinib) FDA Label [Link]
  4. EMA label, Lapatinib [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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. Nelson MH, Dolder CR: A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer. Ther Clin Risk Manag. 2007 Aug;3(4):665-73. [PubMed:18472989]
  4. Tykerb (Lapatinib) FDA Label [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Tap2 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 ...
Gene Name
TAP1
Uniprot ID
Q03518
Uniprot Name
Antigen peptide transporter 1
Molecular Weight
87216.855 Da
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]

Drug created on May 16, 2007 11:27 / Updated on December 14, 2018 16:27