gefitinib   Click here for help

GtoPdb Ligand ID: 4941

Synonyms: Iressa® | ZD 1839 | ZD1839
Approved drug PDB Ligand
gefitinib is an approved drug (FDA (2003), EMA (2009))
Compound class: Synthetic organic
Comment: Gefitinib is an orally active Type-1 kinase inhibitor and was first approved by the US FDA in 2003. Gefitinib has selectivity for the EGFR [5].
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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: gefitinib

gefitinib 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 5
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 68.74
Molecular weight 446.15
XLogP 3.18
No. Lipinski's rules broken 0
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 COc1cc2ncnc(c2cc1OCCCN1CCOCC1)Nc1ccc(c(c1)Cl)F
Isomeric SMILES COc1cc2ncnc(c2cc1OCCCN1CCOCC1)Nc1ccc(c(c1)Cl)F
InChI InChI=1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27)
InChI Key XGALLCVXEZPNRQ-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Used in the treatment of various cancers including those of the breast and lung. In July 2015, the US FDA approved gefitinib as a first-line treatment for metastatic non-small cell lung cancer (NSCLC).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Gefitinib inhibits intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including epidermal growth factor receptor (EGFR), tyrosine kinase activation of which may initiate intracellular signaling events leading to cell proliferation and influencing processes critical to cell survival and tumor progression (e.g., angiogenesis, apoptosis, metastasis). Further studies are required to elucidate the precise mechanism of antineoplastic activity and to determine if any correlation exists between EGFR receptor expression and gefitinib response.
Pharmacokinetics Click here for help
Absorption/Distribution
It takes 3-7h for an oral dose of gefitinib to reach peak plasma concentration, with a bioavailability of 60% (90% bound to serum albumin and α1-acid glycoproteins). Gefitinib is known to cross the placenta. Rat data indicate that this drug and its metabolites are found in milk. It is not known whether this distribution also occurrs in human milk.
Biotransformation/Metabolism
CYP3A4 in the liver is the primary matabolizing enzyme.
Elimination
Gefitinib is eliminated mainly as metabolites via feces (86%) and urine (<4%).
Population pharmacokinetics
No clinically significant change in pharmacokinetics due to age, weight, ethnicity or gender has been reported, but safety and efficacy has not been established in children <18yrs old.
Organ function impairment
Not unexpectedly, since gefitinib is cleared principally by the liver, patients with hepatic impairment exhibit increased systemic exposure to the drug. However, in patients with moderate to severe elevations of hepatic enzymes and liver metastases, pharmacokinetic profile is similar to that in patients without hepatic abnormalities. The effect of severe renal impairment on pharmacokinetics has not been not determined, so advice is to use with caution
External links Click here for help
For extended ADME data see the following:

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