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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2D Structure
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Physico-chemical Properties
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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
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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)
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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
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.
Lapatinib is primarily metabolized by CYP3A4 and CYP3A5, with minor metabolism by CYP2C19 and CYP2C8.
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.
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