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Details

Stereochemistry ACHIRAL
Molecular Formula C24H25ClFN5O2.H2O
Molecular Weight 487.954
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DACOMITINIB

SMILES

O.COC1=CC2=C(C=C1NC(=O)\C=C\CN3CCCCC3)C(NC4=CC(Cl)=C(F)C=C4)=NC=N2

InChI

InChIKey=BSPLGGCPNTZPIH-IPZCTEOASA-N
InChI=1S/C24H25ClFN5O2.H2O/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);1H2/b6-5+;

HIDE SMILES / InChI

Molecular Formula C24H25ClFN5O2
Molecular Weight 469.939
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Dacomitinib is an oral, once-daily, pan-HER inhibitor. It is an irreversible inhibitor of HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases. Dacomtinib is being evaluated in phase 3 clinical trials against nonsmall-cell lung cancer. Direct comparison with erlotinib did not show superiority of dacomtinib, but subgroup analysis have demonstrated that subgroup with exon 19 deletion had favorable outcomes with dacomitinib. In addition to nonsmall-cell lung cancer dacomtinib is being evaluated against esophagus, head and neck and other neoplasms. Due to its ability to pass through blood-brain barrier, dacomitinib can be used to treat brain tumors.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
6.0 nM [IC50]
45.7 nM [IC50]
73.7 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VIZIMPRO
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
108 ng/mL
45 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens
105 ng/mL
60 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2213 ng × h/mL
45 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens
1720 ng × h/mL
60 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
70 h
45 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
45 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens
2%
60 mg 1 times / day steady-state, oral
DACOMITINIB plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
In phase III study against non small cell lung cancer dacomitinib was administered orally at a dose 45 mg a day.
Route of Administration: Oral
In Vitro Use Guide
Cells were seeded in duplicate at 5 × 103 to 5 × 104 cells per well in 24-well plates. A day after plating, dacomitinib was added at 10 μmol/L and 2-fold dilutions over 12 concentrations were carried out to generate a dose–response curve. Control wells without the drug were also seeded. The cells were counted on day 1 when the drug was added, as well as after 6 days when the experiment ended. After the trypsinization cells were placed in an Isotone solution and immediately counted using a Coulter Z1 particle counter (Beckman Coulter, Inc.). The suspension cultures were counted using a Coulter Vi-Cell counter (Beckman Coulter, Inc.). As a group, HER2-amplified cell lines were most sensitive to growth inhibition by dacomitinib (IC50 < 1 μmol/L in 14 of 16 lines).
Substance Class Chemical
Record UNII
5092U85G58
Record Status Validated (UNII)
Record Version