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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2D Structure
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Physico-chemical Properties
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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
SMILES / InChI / InChIKey
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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
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
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Wikipedia Dacomitinib

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Tocris
Dacomitinib
Cat. No. 6231