lapatinib   Click here for help

GtoPdb Ligand ID: 5692

Synonyms: FMM | GW 572016 | GW572016 | Tykerb® | Tyverb®
Approved drug PDB Ligand
lapatinib is an approved drug (FDA (2007), EMA (2008))
Compound class: Synthetic organic
Comment: Lapatinib is a Type-1.5 kinase inhibitor and was first approved by the US FDA in 2007.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: lapatinib

lapatinib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 114.73
Molecular weight 580.13
XLogP 5.41
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Fc1cccc(c1)COc1ccc(cc1Cl)Nc1ncnc2c1cc(cc2)c1ccc(o1)CNCCS(=O)(=O)C
Isomeric SMILES Fc1cccc(c1)COc1ccc(cc1Cl)Nc1ncnc2c1cc(cc2)c1ccc(o1)CNCCS(=O)(=O)C
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)
InChI Key BCFGMOOMADDAQU-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Used in the treatment of breast cancer and other cancers with solid tumours. Lapatinib is used as a combination therapy for advanced or metastatic breast cancer.
Marketed formulations contain lapatinib ditosylate (PubChem CID 9941095).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Lapatinib is an inhibitor of the intracellular tyrosine kinase domains of both EGFR (ErbB1) and HER2 (ErbB2) receptors in vitro and in animal models. The precise mechanism of clinical antitumor action of lapatinib is not fully defined and its inhibitory effects on other tyrosine kinase receptors remains to be fully characterized.
Pharmacokinetics Click here for help
Absorption/Distribution
Oral dose of lapatinib reaches peak circulatory concentration after 4h with steady state reached in 6-7 days. Bioavailability reaches 60% increasing to almost 100% when administered with food. 93% circulates bound to serum albumim and α1-acid glycoproteins.
Biotransformation/Metabolism
Lapatinib is primarily metabolized by CYP3A4 and CYP3A5, with minor metabolism by CYP2C19 and CYP2C8.
Elimination
The primary route of excretion for lapatinib and its metabolites is in feces (>90% as metabolites). Less than 2% is eliminated in urine.
Population pharmacokinetics
The effects of age, gender and race on the pharmacokinetics of lapatinib have not been studied. The pharmacokinetics of lapatinib have not been studied in children.
Organ function impairment
Because less than 2% of an administered dose is eliminated by the kidneys, renal impairment is unlikely to affect the pharmacokinetics. In patients with moderate and severe hepatic impairment total exposure increased after a single dose by approximately 14% and 63% respectively so exercise caution and consider dose reduction in patients with severe hepatic impairment.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)