Details of the Drug

General Information of Drug (ID: DMOH8VY)

Drug Name
Dacomitinib
Synonyms PF-00299804
Indication
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [1]
Affected Organisms
Humans and other mammals
ATC Code
L01EB07: Dacomitinib
L01EB: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
L01E: PROTEIN KINASE INHIBITORS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 469.9
Logarithm of the Partition Coefficient (xlogp) 4.4
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 3000 mcgh/L []
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 2 mcg/L []
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1.5 h []
Bioavailability
The bioavailability of drug is 60-80% []
Clearance
The clearance of drug is 27.06 L/h [2]
Elimination
79% is recovered in feces, and 3% is recovered in urine [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 70 hours [3]
Metabolism
The drug is metabolized via the glutathione and cytochrome P450 enzymes [4]
Vd
The volume of distribution (Vd) of drug is 2415 L [2]
Chemical Identifiers
Formula
C24H25ClFN5O2
IUPAC Name
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide
Canonical SMILES
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4
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+
InChIKey
LVXJQMNHJWSHET-AATRIKPKSA-N
Cross-matching ID
PubChem CID
11511120
ChEBI ID
CHEMBL2110732
CAS Number
1110813-31-4
UNII
2XJX250C20
DrugBank ID
DB11963
TTD ID
D06XXH
VARIDT ID
DR00109
INTEDE ID
DR0407
ACDINA ID
D00982
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Antagonist [5]
Erbb2 tyrosine kinase receptor (HER2) TT6EO5L ERBB2_HUMAN Antagonist [6]
Erbb4 tyrosine kinase receptor (Erbb-4) TT0JESD ERBB4_HUMAN Antagonist [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2D6 (CYP2D6)
Main DME 		DECB0K3 CP2D6_HUMAN Substrate [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-small-cell lung cancer
ICD Disease Classification 2C25.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Epidermal growth factor receptor (EGFR) DTT EGFR 5.84E-05 0.32 0.55
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 1.14E-01 -7.61E-02 -3.24E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 4.60E-34 -1.33E+00 -2.50E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.04E-04 -9.90E-02 -3.91E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dacomitinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Oliceridine DM6MDCF Major Decreased metabolism of Dacomitinib caused by Oliceridine mediated inhibition of CYP450 enzyme. Acute pain [MG31] [8]
Pexidartinib DMS2J0Z Major Decreased metabolism of Dacomitinib caused by Pexidartinib mediated inhibition of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [9]
Deutetrabenazine DMUPFLI Major Decreased metabolism of Dacomitinib caused by Deutetrabenazine mediated inhibition of CYP450 enzyme. Dystonic disorder [8A02] [10]
Arry-162 DM1P6FR Moderate Decreased clearance of Dacomitinib due to the transporter inhibition by Arry-162. Melanoma [2C30] [11]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 2 E00446 2723854 Colorant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Dacomitinib 15 mg tablet 15 mg Tablet Oral
Dacomitinib 30 mg tablet 30 mg Tablet Oral
Dacomitinib 45 mg tablet 45 mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
2 Chen X, Jiang J, Giri N, Hu P: Phase 1 study to investigate the pharmacokinetic properties of dacomitinib in healthy adult Chinese subjects genotyped for CYP2D6. Xenobiotica. 2018 May;48(5):459-466. doi: 10.1080/00498254.2017.1342881. Epub 2017 Aug 18.
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Wijnsma KL, Ter Heine R, Moes DJAR, Langemeijer S, Schols SEM, Volokhina EB, van den Heuvel LP, Wetzels JFM, van de Kar NCAJ, Bruggemann RJ: Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab. Clin Pharmacokinet. 2019 Jul;58(7):859-874. doi: 10.1007/s40262-019-00742-8.
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1797).
6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7422).
7 Phase 1 study to investigate the pharmacokinetic properties of dacomitinib in healthy adult Chinese subjects genotyped for CYP2D6. Xenobiotica. 2018 May;48(5):459-466.
8 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
9 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
10 Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
11 Cerner Multum, Inc. "Australian Product Information.".