dacomitinib   Click here for help

GtoPdb Ligand ID: 7422

Synonyms: PF-00299804 | PF00299804 | Vizimpro®
Approved drug PDB Ligand
dacomitinib is an approved drug (FDA (2018), EMA (2019))
Compound class: Synthetic organic
Comment: Dacomitinib is a second-generation, irreversible pan inhibitor of HER tyrosine kinases (EGFR, and ERBBs) that was developed by Pfizer.
Results from the ARCHER 1050 Phase 3 randomised, open-label trial (NCT01774721) that directly compared dacomitinib against gefitinib, as first-line treatment for patients with EGFR-mutation +ve non-small-cell lung cancer (NSCLC), reported that dacomitinib significantly increased progression-free survival and overall survival compared to gefitinib [3]. Dacomitinib's use may be limited in NSCLC patients with brain metastases, as these patients were excluded from the trial because dacomitinib's ability to cross the blood-brain-barrier has not been fully confirmed. This is unlike osimertinib (another third-generation irreversible EGFR inhibitor) which has confirmed brain penetrance, and which does not appear to cause the same dose-limiting toxicities that afflict dacomitinib. In April 2018 both the FDA and EMA accepted regulatory submissions (New Drug Application and Marketing Authorization Application respectively) for review of dacomitinib as a therapy for metastatic NSCLC with EGFR-activating mutations. The FDA granted Priority Review status for the submitted NDA.

SARS-CoV-2: A high-throughput screen identified potential anti-SARS-CoV-2 activity in cell infection assays [2].
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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

dacomitinib 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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 8
Topological polar surface area 79.38
Molecular weight 469.17
XLogP 3.97
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1cc2ncnc(c2cc1NC(=O)C=CCN1CCCCC1)Nc1ccc(c(c1)Cl)F
Isomeric SMILES COc1cc2ncnc(c2cc1NC(=O)/C=C/CN1CCCCC1)Nc1ccc(c(c1)Cl)F
InChI InChI=1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+
InChI Key LVXJQMNHJWSHET-AATRIKPKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes. FDA (2018)  |  EMA (2019)
IUPAC Name Click here for help
(E)-N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide
International Nonproprietary Names Click here for help
INN number INN
9314 dacomitinib
Synonyms Click here for help
PF-00299804 | PF00299804 | Vizimpro®
Database Links Click here for help
CAS Registry No. 1110813-31-4
ChEMBL Ligand CHEMBL2110732
DrugCentral Ligand 5297
GtoPdb PubChem SID 178103994
PubChem CID 11511120
RCSB PDB Ligand 1C9
Search Google for chemical match using the InChIKey LVXJQMNHJWSHET-AATRIKPKSA-N
Search Google for chemicals with the same backbone LVXJQMNHJWSHET
Search PubMed clinical trials dacomitinib
Search PubMed titles dacomitinib
Search PubMed titles/abstracts dacomitinib
UniChem Compound Search for chemical match using the InChIKey LVXJQMNHJWSHET-AATRIKPKSA-N
UniChem Connectivity Search for chemical match using the InChIKey LVXJQMNHJWSHET-AATRIKPKSA-N
Wikipedia Dacomitinib

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MedChemExpress
Dacomitinib (links to external site)
Cat. No. HY-13272