dacomitinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5297 1110813-31-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • dacomitinib
  • dacomitinib hydrate
  • vizimpro
  • PF-00299804-03
  • PF-00299804
  • PF-299
  • PF-299804
  • PF-804
Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations.
  • Molecular weight: 469.95
  • Formula: C24H25ClFN5O2
  • CLOGP: 5.75
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 2
  • TPSA: 79.38
  • ALOGS: -4.73
  • ROTB: 7
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
45 mg O

ADMET properties:

PropertyValueReference
S (Water solubility) 0.06 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.123 Moderate 0.73
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.698 Moderate 0.73
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 15.668 10^-6 cm/s Moderate 0.73
dh-clint Dog hepatocyte intrinsic clearance 5.916 uL/min/10^6 cells Moderate 0.73
dppb Dog plasma protein binding (% unbound) 3.570 % Moderate 0.73
fcs-ppb Fetal calf serum protein binding (% unbound) 15.220 % Moderate 0.73
herg hERG pIC50 5.713 pIC50 Moderate 0.73
hh-clint Human hepatocyte intrinsic clearance 2.455 uL/min/10^6 cells Moderate 0.73
hlm-clint Human liver microsomal intrinsic clearance 19.999 uL/min/mg protein Moderate 0.73
hppb Human plasma protein binding (% unbound) 3.530 % Moderate 0.73
kinase-safety-class ABL1,ABL2,ACVR2B,AKT3,ALK,AURKA,AURKB,AXL,BLK,BMX,BRAF,BTK,CAMK2D,CDK5,CHEK1,CSF1R,CSK,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,ERBB4,FGFR1,FLT3,FYN,GAK,ITK,JAK1,KDR,KIT,LCK,LYN,MAP3K1,MAP3K10,MAP3K21,MAP4K2,MAP4K5,MAPK10,MAPK11,MAPK14,MAPK7,MAPKAPK2,MARK4,MET,MKNK1,MKNK2,NTRK1,PAK4,PDK1,PDK2,PDK4,PRKCD,PRKDC,PTK6,RET,RIPK3,SIK2,SIK3,SRC,STK33,SYK,TEK,TTK,YES1 67
kinase-selectivity-class BLK,BRAF,CAMK2D,DDR1,EGFR,EPHA2,EPHB4,ERBB2,ERBB4,KDR,LYN,MAPK7,MET,MKNK1,PDK4,SIK2,STK33,YES1 18
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 12.162 Moderate 0.73
mh-clint Mouse hepatocyte intrinsic clearance 9.162 Moderate 0.73
mppb Mouse plasma protein binding (% unbound) 2.040 Moderate 0.73
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 22.284 Moderate 0.73
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 4.680 % Moderate 0.73
rh-clint Rat hepatocyte intrinsic clearance 8.610 uL/min/10^6 cells Moderate 0.73
rh-fuinc Rat hepatocyte fraction unbound in incubation 11.250 % Moderate 0.73
rppb Rat plasma protein binding (% unbound) 2.530 % Moderate 0.73
solubility-dd Solubility at pH 7.4 in DMSO 4.227 uM Moderate 0.73

Approvals:

DateAgencyCompanyOrphan
Aug. 1, 2019 PMDA PFIZER JAPAN INC.
Sept. 27, 2018 FDA PFIZER INC
Feb. 4, 2019 EMA PFIZER EUROPE MA EEIG

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 75.86 58.29 19 255 44467 90583706
Death 59.00 58.29 28 246 456523 90171650

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 50.00 46.45 14 208 28986 42592127

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neoplasm progression 112.54 42.12 32 589 64563 110524115
Paronychia 84.34 42.12 18 603 11063 110577615
Diarrhoea 50.41 42.12 45 576 1139460 109449218
Death 46.31 42.12 35 586 698834 109889844

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EB07 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:74440 epidermal growth factor receptor antagonist

Related Drugs by ATC class:

L01EB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors 8 drugs
afatiniberlotinibgefitinibicotiniblazertinibmobocertinibolmutinibosimertinib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer, positive for epidermal growth factor receptor expression indication 426964009
EGFR mutation-positive, unresectable or recurrent non-small cell lung cancer indication 703228009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.02 acidic
pKa2 9.12 Basic
pKa3 4.78 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
15MG VIZIMPRO PFIZER N211288 Sept. 27, 2018 RX TABLET ORAL 10596162 Feb. 2, 2026 ADMINISTERING DAILY A UNIT DOSAGE OF AN IRREVERSIBLE EGFR INHIBITOR COVALENTLY BINDING AS CLAIMED FOR 1ST LINE TREATMENT OF GEFITINIB OR ERLOTINIB RESISTANT METASTATIC NSCLC WITH EGFR EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION WITH T790M MUTATION
15MG VIZIMPRO PFIZER N211288 Sept. 27, 2018 RX TABLET ORAL 10603314 Feb. 2, 2026 ADMINISTERING DAILY A UNIT DOSAGE OF AN IRREVERSIBLE EGFR INHIBITOR COVALENTLY BINDING AS CLAIMED FOR 1ST LINE TREATMENT OF GEFITINIB OF ERLOTINIB RESISTANT METASTATIC NSCLC WITH EGFR EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION
30MG VIZIMPRO PFIZER N211288 Sept. 27, 2018 RX TABLET ORAL 10596162 Feb. 2, 2026 ADMINISTERING DAILY A UNIT DOSAGE OF AN IRREVERSIBLE EGFR INHIBITOR COVALENTLY BINDING AS CLAIMED FOR 1ST LINE TREATMENT OF GEFITINIB OR ERLOTINIB RESISTANT METASTATIC NSCLC WITH EGFR EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION WITH T790M MUTATION
30MG VIZIMPRO PFIZER N211288 Sept. 27, 2018 RX TABLET ORAL 10603314 Feb. 2, 2026 ADMINISTERING DAILY A UNIT DOSAGE OF AN IRREVERSIBLE EGFR INHIBITOR COVALENTLY BINDING AS CLAIMED FOR 1ST LINE TREATMENT OF GEFITINIB OF ERLOTINIB RESISTANT METASTATIC NSCLC WITH EGFR EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION
45MG VIZIMPRO PFIZER N211288 Sept. 27, 2018 RX TABLET ORAL 10596162 Feb. 2, 2026 ADMINISTERING DAILY A UNIT DOSAGE OF AN IRREVERSIBLE EGFR INHIBITOR COVALENTLY BINDING AS CLAIMED FOR 1ST LINE TREATMENT OF GEFITINIB OR ERLOTINIB RESISTANT METASTATIC NSCLC WITH EGFR EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION WITH T790M MUTATION
45MG VIZIMPRO PFIZER N211288 Sept. 27, 2018 RX TABLET ORAL 10603314 Feb. 2, 2026 ADMINISTERING DAILY A UNIT DOSAGE OF AN IRREVERSIBLE EGFR INHIBITOR COVALENTLY BINDING AS CLAIMED FOR 1ST LINE TREATMENT OF GEFITINIB OF ERLOTINIB RESISTANT METASTATIC NSCLC WITH EGFR EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR IC50 8.22 SCIENTIFIC LITERATURE DRUG LABEL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR IC50 7.34 SCIENTIFIC LITERATURE DRUG LABEL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR IC50 7.13 SCIENTIFIC LITERATURE DRUG LABEL
Cyclin-G-associated kinase Kinase Kd 6.78 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6 CHEMBL
Tyrosine-protein kinase JAK3 Kinase IC50 5.45 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.44 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 6.96 CHEMBL
Tyrosine-protein kinase Lck Kinase IC50 7.03 CHEMBL
Epidermal growth factor receptor Kinase IC50 8.24 CHEMBL

External reference:

IDSource
5092U85G58 UNII
4037910 VANDF
C2987430 UMLSCUI
CHEBI:132268 CHEBI
1C9 PDB_CHEM_ID
CHEMBL2105719 ChEMBL_ID
11511120 PUBCHEM_CID
DB11963 DRUGBANK_ID
CHEMBL2110732 ChEMBL_ID
D09883 KEGG_DRUG
C525726 MESH_SUPPLEMENTAL_RECORD_UI
7422 IUPHAR_LIGAND_ID
781492009 SNOMEDCT_US
781495006 SNOMEDCT_US
293963 MMSL
35285 MMSL
d08999 MMSL
017767 NDDF
1042385-75-0 SECONDARY_CAS_RN
2058849 RXNORM
5092U85G58 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Vizimpro HUMAN PRESCRIPTION DRUG LABEL 1 0069-0197 TABLET, FILM COATED 15 mg ORAL NDA 28 sections
Vizimpro HUMAN PRESCRIPTION DRUG LABEL 1 0069-1198 TABLET, FILM COATED 30 mg ORAL NDA 28 sections
Vizimpro HUMAN PRESCRIPTION DRUG LABEL 1 0069-2299 TABLET, FILM COATED 45 mg ORAL NDA 28 sections