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Details

Stereochemistry ACHIRAL
Molecular Formula C24H25ClFN5O2
Molecular Weight 469.9398
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DACOMITINIB ANHYDROUS

SMILES

COc1cc2c(cc1N=C(/C(/[H])=C(\[H])/CN3CCCCC3)O)c(ncn2)Nc4ccc(c(c4)Cl)F

InChI

InChIKey=LVXJQMNHJWSHET-AATRIKPKSA-N
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+

HIDE SMILES / InChI

Molecular Formula C24H25ClFN5O2
Molecular Weight 469.9398
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/25939761

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.

Originator

Curator's Comment:: # Pfizer

Approval Year

TargetsConditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
108 ng/mL
45 mg 1 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACOMITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
105 ng/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACOMITINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2213 ng × h/mL
45 mg 1 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACOMITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1720 ng × h/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACOMITINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
70 h
45 mg 1 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACOMITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
45 mg 1 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DACOMITINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Other AEs: Diarrhea, Diarrhea...
Other AEs:
Diarrhea (grade 1-2, 79%)
Diarrhea (grade 3-4, 8%)
Mucosal inflammation (grade 1-2, 40.6%)
Stomatitis (grade 1-2, 40.6%)
Mucosal inflammation (grade 3-4, 4.4%)
Stomatitis (grade 3-4, 4.4%)
Nausea (grade 1-2, 17.7%)
Nausea (grade 3-4, 1.3%)
Constipation (grade 1-2, 13%)
Mouth ulceration (grade 1-2, 12%)
Dermatitis acneiform (grade 1-2, 46%)
Rash (grade 1-2, 46%)
Rash maculo-papular (grade 1-2, 46%)
Dermatitis acneiform (grade 3-4, 23%)
Rash (grade 3-4, 23%)
Rash maculo-papular (grade 3-4, 23%)
Nail infection (grade 1-2, 56%)
Nail toxicity (grade 1-2, 56%)
Onychoclasis (grade 1-2, 56%)
Onycholysis (grade 1-2, 56%)
Onychomadesis (grade 1-2, 56%)
Paronychia (grade 1-2, 56%)
Nail infection (grade 3-4, 8%)
Nail toxicity (grade 3-4, 8%)
Onychoclasis (grade 3-4, 8%)
Onycholysis (grade 3-4, 8%)
Onychomadesis (grade 3-4, 8%)
Paronychia (grade 3-4, 8%)
Dry skin (grade 1-2, 28.2%)
Xerosis (grade 1-2, 28.2%)
Dry skin (grade 3-4, 1.8%)
Xerosis (grade 3-4, 1.8%)
Alopecia (grade 1-2, 22.6%)
Alopecia (grade 3-4, 0.4%)
Pruritus (grade 1-2, 20.1%)
Pruritus generalized (grade 1-2, 20.1%)
Rash pruritic (grade 1-2, 20.1%)
Pruritus (grade 3-4, 0.9%)
Pruritus generalized (grade 3-4, 0.9%)
Rash pruritic (grade 3-4, 0.9%)
Palmar-plantar erythrodysesthesia syndrome (grade 1-2, 14.1%)
Palmar-plantar erythrodysesthesia syndrome (grade 3-4, 0.9%)
Dermatitis (grade 1-2, 9.2%)
Dermatitis (grade 3-4, 1.8%)
Decreased appetite (grade 1-2, 27.9%)
Decreased appetite (grade 3-4, 3.1%)
Weight decreased (grade 1-2, 23.8%)
Weight decreased (grade 3-4, 2.2%)
Cough (grade 1-2, 21%)
Epistaxis (grade 1-2, 19%)
Nasal inflammation (grade 1-2, 19%)
Nasal mucosal disorder (grade 1-2, 19%)
Nasal mucosal ulcer (grade 1-2, 19%)
Rhinitis (grade 1-2, 19%)
Dyspnea (grade 1-2, 10.8%)
Dyspnea (grade 3-4, 2.2%)
Upper respiratory tract infection (grade 1-2, 10.7%)
Upper respiratory tract infection (grade 3-4, 1.3%)
Chest pain (grade 1-2, 10%)
Conjunctivitis (grade 1-2, 19%)
Pain in extremity (grade 1-2, 14%)
Musculoskeletal pain (grade 1-2, 11.1%)
Musculoskeletal pain (grade 3-4, 0.9%)
Asthenia (grade 1-2, 10.8%)
Asthenia (grade 3-4, 2.2%)
Insomnia (grade 1-2, 10.6%)
Insomnia (grade 3-4, 0.4%)
Fatigue (all grades, 9%)
Skin fissures (all grades, 9%)
Hypertrichosis (all grades, 1.3%)
Skin exfoliation (all grades, 3.5%)
Vomiting (all grades, 9%)
Dysgeusia (all grades, 7%)
Interstitial lung disease (all grades, 2.6%)
Keratitis (all grades, 1.8%)
Dehydration (all grades, 1.3%)
Anemia (grade 1-2, 43.1%)
Anemia (grade 3-4, 0.9%)
Lymphopenia (grade 1-2, 36%)
Lymphopenia (grade 3-4, 6%)
Hypoalbuminemia (grade 1-2, 44%)
ALT increased (grade 1-2, 38.6%)
ALT increased (grade 3-4, 1.4%)
Hyperglycemia (grade 1-2, 35%)
Hyperglycemia (grade 3-4, 1%)
AST increased (grade 1-2, 34.5%)
AST increased (grade 3-4, 0.5%)
Hypocalcemia (grade 1-2, 31.6%)
Hypocalcemia (grade 3-4, 1.4%)
Hypokalemia (grade 1-2, 22%)
Hypokalemia (grade 3-4, 7%)
Hyponatremia (grade 1-2, 23.1%)
Hyponatremia (grade 3-4, 2.9%)
Creatinine increased (grade 1-2, 24%)
Alkaline phosphatase increased (grade 1-2, 21.5%)
Alkaline phosphatase increased (grade 3-4, 0.5%)
Hypomagnesemia (grade 1-2, 21.5%)
Hypomagnesemia (grade 3-4, 0.5%)
Hyperbilirubinemia (grade 1-2, 15.5%)
Hyperbilirubinemia (grade 3-4, 0.5%)
Sources:
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Maculopapular rash, Interstitial lung disease...
AEs leading to
discontinuation/dose reduction:
Maculopapular rash (1%)
Interstitial lung disease (1%)
Pneumonitis (2%)
Stomatitis (1%)
Diarrhea (1%)
Dermatitis acneiform (1%)
Bronchopulmonary aspergillosis (0.4%)
Cerebral infarction (0.4%)
Infection (0.4%)
Keratitis (0.4%)
Keratolysis exfoliativa acquired (0.4%)
Liver injury (0.4%)
Lung infection (0.4%)
Lymphocyte count decreased (0.4%)
Malaise (0.4%)
Malnutrition (0.4%)
Muscular weakness (0.4%)
Respiratory failure (0.4%)
Urinary tract infection (0.4%)
Sources:
60 mg 1 times / day steady, oral
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy
AEs

AEs

AESignificanceDosePopulation
Dehydration all grades, 1.3%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypertrichosis all grades, 1.3%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Keratitis all grades, 1.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Interstitial lung disease all grades, 2.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Skin exfoliation all grades, 3.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dysgeusia all grades, 7%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Fatigue all grades, 9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Skin fissures all grades, 9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Vomiting all grades, 9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Chest pain grade 1-2, 10%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Insomnia grade 1-2, 10.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Upper respiratory tract infection grade 1-2, 10.7%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Asthenia grade 1-2, 10.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dyspnea grade 1-2, 10.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Musculoskeletal pain grade 1-2, 11.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Mouth ulceration grade 1-2, 12%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Constipation grade 1-2, 13%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Pain in extremity grade 1-2, 14%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Palmar-plantar erythrodysesthesia syndrome grade 1-2, 14.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hyperbilirubinemia grade 1-2, 15.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nausea grade 1-2, 17.7%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Conjunctivitis grade 1-2, 19%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Epistaxis grade 1-2, 19%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nasal inflammation grade 1-2, 19%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nasal mucosal disorder grade 1-2, 19%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nasal mucosal ulcer grade 1-2, 19%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rhinitis grade 1-2, 19%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Pruritus generalized grade 1-2, 20.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Pruritus grade 1-2, 20.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rash pruritic grade 1-2, 20.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Cough grade 1-2, 21%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Alkaline phosphatase increased grade 1-2, 21.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypomagnesemia grade 1-2, 21.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypokalemia grade 1-2, 22%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Alopecia grade 1-2, 22.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hyponatremia grade 1-2, 23.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Weight decreased grade 1-2, 23.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Creatinine increased grade 1-2, 24%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Decreased appetite grade 1-2, 27.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dry skin grade 1-2, 28.2%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Xerosis grade 1-2, 28.2%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypocalcemia grade 1-2, 31.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
AST increased grade 1-2, 34.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hyperglycemia grade 1-2, 35%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Lymphopenia grade 1-2, 36%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
ALT increased grade 1-2, 38.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Mucosal inflammation grade 1-2, 40.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Stomatitis grade 1-2, 40.6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Anemia grade 1-2, 43.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypoalbuminemia grade 1-2, 44%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dermatitis acneiform grade 1-2, 46%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rash maculo-papular grade 1-2, 46%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rash grade 1-2, 46%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nail infection grade 1-2, 56%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nail toxicity grade 1-2, 56%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Onychoclasis grade 1-2, 56%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Onycholysis grade 1-2, 56%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Onychomadesis grade 1-2, 56%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Paronychia grade 1-2, 56%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Diarrhea grade 1-2, 79%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dermatitis grade 1-2, 9.2%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Alopecia grade 3-4, 0.4%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Insomnia grade 3-4, 0.4%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
AST increased grade 3-4, 0.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Alkaline phosphatase increased grade 3-4, 0.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hyperbilirubinemia grade 3-4, 0.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypomagnesemia grade 3-4, 0.5%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Anemia grade 3-4, 0.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Musculoskeletal pain grade 3-4, 0.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Palmar-plantar erythrodysesthesia syndrome grade 3-4, 0.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Pruritus generalized grade 3-4, 0.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Pruritus grade 3-4, 0.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rash pruritic grade 3-4, 0.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hyperglycemia grade 3-4, 1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nausea grade 3-4, 1.3%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Upper respiratory tract infection grade 3-4, 1.3%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
ALT increased grade 3-4, 1.4%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypocalcemia grade 3-4, 1.4%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dermatitis grade 3-4, 1.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dry skin grade 3-4, 1.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Xerosis grade 3-4, 1.8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Asthenia grade 3-4, 2.2%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dyspnea grade 3-4, 2.2%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Weight decreased grade 3-4, 2.2%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hyponatremia grade 3-4, 2.9%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dermatitis acneiform grade 3-4, 23%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rash maculo-papular grade 3-4, 23%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Rash grade 3-4, 23%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Decreased appetite grade 3-4, 3.1%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Mucosal inflammation grade 3-4, 4.4%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Stomatitis grade 3-4, 4.4%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Lymphopenia grade 3-4, 6%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Hypokalemia grade 3-4, 7%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Diarrhea grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nail infection grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Nail toxicity grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Onychoclasis grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Onycholysis grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Onychomadesis grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Paronychia grade 3-4, 8%
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Bronchopulmonary aspergillosis 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Cerebral infarction 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Infection 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Keratitis 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Keratolysis exfoliativa acquired 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Liver injury 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Lung infection 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Lymphocyte count decreased 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Malaise 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Malnutrition 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Muscular weakness 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Respiratory failure 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Urinary tract infection 0.4%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Dermatitis acneiform 1%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Diarrhea 1%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Interstitial lung disease 1%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Maculopapular rash 1%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Stomatitis 1%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
Pneumonitis 2%
Disc. AE
45 mg 1 times / day multiple, oral
MTD
Dose: 45 mg, 1 times / day
Route: oral
Route: multiple
Dose: 45 mg, 1 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: dacomitnib increased dextromethorphan AUC by 362% and Cmax by 973%
Page: 55
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Irreversible protein kinase inhibitors: balancing the benefits and risks.
2012 Jul 26
Patents

Sample Use Guides

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
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
Created
by admin
on Sat Jun 26 08:33:15 UTC 2021
Edited
by admin
on Sat Jun 26 08:33:15 UTC 2021
Record UNII
2XJX250C20
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DACOMITINIB ANHYDROUS
Common Name English
(2E)-N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-METHOXYQUINAZOLIN-6-YL)-4-PIPERIDIN-1-YLBUT-2-ENAMIDE
Systematic Name English
DACOMITINIB [WHO-DD]
Common Name English
PF-00299804
Code English
DACOMITINIB [INN]
Common Name English
Code System Code Type Description
INN
9314
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
CAS
1110813-31-4
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
RXCUI
2058848
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
NCI_THESAURUS
C171723
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
FDA UNII
2XJX250C20
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
PUBCHEM
11511120
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
EPA CompTox
1110813-31-4
Created by admin on Sat Jun 26 08:33:16 UTC 2021 , Edited by admin on Sat Jun 26 08:33:16 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
The reversal effect on ABCB1-overexpressing cells is more potent than that on ABCG2-overexpressing cells. Dacomitinib at 1.0??M significantly reversed drug resistance mediated by ABCB1 and ABCG2, but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and ABCG2-overexpressing cell lines.
BINDING
MAY BE CLINICALLY SIGNIFICANT
TARGET -> INHIBITOR
IRREVERSIBLE INHIBITOR
TRANSPORTER -> INHIBITOR
The reversal effect on ABCB1-overexpressing cells is more potent than that on ABCG2-overexpressing cells. Dacomitinib at 1.0??M significantly reversed drug resistance mediated by ABCB1 and ABCG2, but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and ABCG2-overexpressing cell lines.
BINDING
MAY BE CLINICALLY SIGNIFICANT
METABOLIC ENZYME -> SUBSTRATE
IN-VITRO
METABOLIC ENZYME -> SUBSTRATE
IN-VITRO
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
MINOR
FECAL
METABOLITE -> PARENT
In addition, it is likely that dacomitinib underwent glutathione conjugation with subsequent hydrolysis to form the cysteine conjugate (M2).
MAJOR
FECAL
METABOLITE -> PARENT
MINOR
FECAL
METABOLITE ACTIVE -> PARENT
Concentrations of PF-05199265 peaked at 6 h post-dose.
MAJOR
PLASMA
METABOLITE ACTIVE -> PARENT
MAJOR
FECAL; PLASMA
METABOLITE ACTIVE -> PARENT
Fecal homogenate extracts indicated that metabolism of [14C] dacomitinib was similar and extensive in all the 6 subjects. The four most abundant drugrelated components were dacomitinib (20 %), PF-05199265 (20 %), a cysteine conjugate (M2; 9.5 %), and a monooxygenated metabolite (M7; 5.1 %)
MAJOR
FECAL
Related Record Type Details
ACTIVE MOIETY