Identification
- Summary
Dacomitinib is a medication used to treat non small cell lung cancer with EGFR exon 19 deletion of exon 21 L858R substitution.
- Brand Names
- Vizimpro
- Generic Name
- Dacomitinib
- DrugBank Accession Number
- DB11963
- Background
Dacomitinib, designed as (2E)-N-16-4-(piperidin-1-yl) but-2-enamide, is an oral highly selective quinazalone part of the second-generation tyrosine kinase inhibitors which are characterized by the irreversible binding at the ATP domain of the epidermal growth factor receptor family kinase domains.2
Dacomitinib was developed by Pfizer Inc and approved by the FDA on September 27, 2018.14 Some evidence in the literature suggests the therapeutic potential of dacomitinib in the epithelial ovarian cancer model1, although further investigations are needed.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Dacomitinib (DB11963)
- Weight
- Average: 469.939
Monoisotopic: 469.168080981 - Chemical Formula
- C24H25ClFN5O2
- Synonyms
- Dacomitinib
- Dacomitinib anhydrous
- Dacomitinibum
- External IDs
- PF-00299804
Pharmacology
- Indication
Dacomitinib is indicated as the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as verified by an FDA-approved test.15
Lung cancer is the leading cause of cancer death and NSCLC accounts for 85% of lung cancer cases. From the cases of NSCLC, approximately 75% of the patients present a late diagnosis with metastatic and advanced disease which produces a survival rate of 5%. The presence of a mutation in EGFR accounts for more than the 60% of the NSCLC cases and the overexpression of EGFR is associated with frequent lymph node metastasis and poor chemosensitivity.10,11
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic non-small cell lung cancer •••••••••••• •••• •••• •• •••••••• ••••••••• ••••• •••••••• •• •••• •• ••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Preclinical data suggested that dacomitinib increases the inhibition of the epidermal growth factor receptor kinase domain as well as the activity in cell lines harboring resistance mutations such as T790M. This activity further produced a significant reduction of EGFR phosphorylation and cell viability. In these studies, non-small cell lymphoma cancer cell lines with L858R/T790M mutations where used and an IC50 of about 280 nmol/L was observed.3
In clinical trials with patients with advanced non-small cell lung carcinoma who progressed after chemotherapy, there was an objective response rate of 5% with a progression-free survival of 2.8 months and an overall survival of 9.5 months. As well, phase I/II studies showed positive dacomitinib activity despite prior failure with tyrosine kinase inhibitors.2
Phase III clinical trials (ARCHER 1050), done in patients suffering from advanced or metastatic non-small cell lung carcinoma with EGFR-activating mutations, reported a significant improvement in progression-free survival when compared with gefitinib.8
- Mechanism of action
Dacomitinib is an irreversible small molecule inhibitor of the activity of the human epidermal growth factor receptor (EGFR) family (EGFR/HER1, HER2, and HER4) tyrosine kinases. It achieves irreversible inhibition via covalent bonding to the cysteine residues in the catalytic domains of the HER receptors.4 The affinity of dacomitinib has been shown to have an IC50 of 6 nmol/L.2
The ErbB or epidermal growth factor (EGF) family plays a role in tumor growth, metastasis, and treatment resistance by activating downstream signal transduction pathways such as such as Ras-Raf-MAPK, PLCgamma-PKC-NFkB and PI3K/AKT through the tyrosine kinase-driven phosphorylation at the carboxy-terminus.1 Around 40% of cases show amplification of EGFR gene and 50% of the cases present the EGFRvIII mutation which represents a deletion that produces a continuous activation of the tyrosine kinase domain of the receptor.9
Target Actions Organism AEpidermal growth factor receptor inhibitorHumans - Absorption
Dacomitinib has shown a linear kinetics after single and multiple dose range studies. The absorption and distribution do not seem to be affected by food or the consumption of antacids. The peak plasma concentration after a dosage of 45 mg for 4 days is of 104 ng/ml.5 The reported AUC0-24h and tmax are of 2213 ng.h/mL and 6 hours, respectively. As well, following oral administration, the absolute oral bioavailability is 80% Label.
- Volume of distribution
The volume of distribution of dacomitinib was reported to be of 2415 L.12
- Protein binding
Dacomitinib is known to present a protein binding of 98%.13
- Metabolism
Dacomitinib presents an oxidative and conjugative metabolism marked mainly by the activity of glutathione and cytochrome P450 enzymes.5 After metabolism, its major circulating metabolite is an O-desmethyl dacomitinib form named PF-05199265.7 This metabolite has been shown to be formed by an oxidative step by CYP2D6 and to a smaller extent by CYP2C9. The following steps of the metabolism are mainly mediated by CYP3A4 for the formation of smaller metabolites.12
From these metabolic studies, it was shown that dacomitinib inhibited strongly the activities of CYP2D6.6
Hover over products below to view reaction partners
- Route of elimination
From the administered dose, 79% is recovered in feces, from which 20% represents the unmodified form of dacomitinib, and 3% is recovered in urine, from which <1% is represented by the unchanged form.12
- Half-life
Dacomitinib is reported to have a very large half-life of 70 hours.13
- Clearance
The geometric apparent clearance of dacomitinib is 27.06 L/h.12
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The maximum asymptomatic dose in rats was 50 mg/kg MSDS. In animal studies, dacomitinib was shown to induce embryo-fetal toxicity, as demonstrated by an increased incidence of a post-implantation loss and reduced fetal body weight at doses resulting in exposures near the exposure at the 45mg human dose following administration in rats during the period of organogenesis. On the other hand, dacomitinib was showed to lack a mutagenic potential in a bacterial reverse mutation assay, in human lymphocyte chromosome aberration assay and in clastogenic or aneugenic in vivo rat bone marrow micronucleus assay.Label
The dose-limiting and overdose toxicities include stomatitis, rash, palmar-plantar erythrodysesthesia syndrome, dehydration, paronychia, and diarrhea. From these findings, the maximum tolerated dose (defined by the dose in which the dose-limiting toxicities did not exceed 33%) is 45 mg.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Dacomitinib. Abametapir The serum concentration of Dacomitinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Dacomitinib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Dacomitinib. Abiraterone The metabolism of Dacomitinib can be decreased when combined with Abiraterone. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of dacomitinib.
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of dacomitinib.
- Take at the same time every day.
- Take separate from antacids. Take dacomitinib at least 6 hours before or 10 hours after administering antacids.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Dacomitinib monohydrate 5092U85G58 1042385-75-0 BSPLGGCPNTZPIH-IPZCTEOASA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Vizimpro Tablet, film coated 15 mg/1 Oral U.S. Pharmaceuticals 2019-02-01 Not applicable US 
Vizimpro Tablet 30 mg Oral Pfizer Canada Ulc 2019-04-22 2021-11-24 Canada 
Vizimpro Tablet, film coated 30 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2018-10-04 Not applicable US Vizimpro Tablet, film coated 15 mg Oral Pfizer Europe Ma Eeig 2020-12-16 Not applicable EU 
Vizimpro Tablet 15 mg Oral Pfizer Canada Ulc 2019-04-22 2021-11-24 Canada
Categories
- ATC Codes
- L01EB07 — Dacomitinib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strong)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- OCT1 inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Protein Kinase Inhibitors
- Quinazolines
- Tyrosine Kinase Inhibitors
- UGT1A1 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Quinazolinamines
- Alternative Parents
- Methoxyanilines / N-arylamides / Anisoles / Chlorobenzenes / Fluorobenzenes / Aminopyrimidines and derivatives / Alkyl aryl ethers / Imidolactams / Aryl chlorides / Aryl fluorides show 13 more
- Substituents
- Alkyl aryl ether / Amine / Amino acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide show 31 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2XJX250C20
- CAS number
- 1110813-31-4
- InChI Key
- LVXJQMNHJWSHET-AATRIKPKSA-N
- 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+
- IUPAC Name
- (2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}-4-(piperidin-1-yl)but-2-enamide
- SMILES
- COC1=C(NC(=O)\C=C\CN2CCCCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C1
References
- General References
- Momeny M, Zarrinrad G, Moghaddaskho F, Poursheikhani A, Sankanian G, Zaghal A, Mirshahvaladi S, Esmaeili F, Eyvani H, Barghi F, Sabourinejad Z, Alishahi Z, Yousefi H, Ghasemi R, Dardaei L, Bashash D, Chahardouli B, Dehpour AR, Tavakkoly-Bazzaz J, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH: Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells. Sci Rep. 2017 Jun 23;7(1):4204. doi: 10.1038/s41598-017-04147-0. [Article]
- Brzezniak C, Carter CA, Giaccone G: Dacomitinib, a new therapy for the treatment of non-small cell lung cancer. Expert Opin Pharmacother. 2013 Feb;14(2):247-53. doi: 10.1517/14656566.2013.758714. Epub 2013 Jan 7. [Article]
- Engelman JA, Zejnullahu K, Gale CM, Lifshits E, Gonzales AJ, Shimamura T, Zhao F, Vincent PW, Naumov GN, Bradner JE, Althaus IW, Gandhi L, Shapiro GI, Nelson JM, Heymach JV, Meyerson M, Wong KK, Janne PA: PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007 Dec 15;67(24):11924-32. doi: 10.1158/0008-5472.CAN-07-1885. [Article]
- Fry DW, Bridges AJ, Denny WA, Doherty A, Greis KD, Hicks JL, Hook KE, Keller PR, Leopold WR, Loo JA, McNamara DJ, Nelson JM, Sherwood V, Smaill JB, Trumpp-Kallmeyer S, Dobrusin EM: Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):12022-7. [Article]
- Janne PA, Boss DS, Camidge DR, Britten CD, Engelman JA, Garon EB, Guo F, Wong S, Liang J, Letrent S, Millham R, Taylor I, Eckhardt SG, Schellens JH: Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors. Clin Cancer Res. 2011 Mar 1;17(5):1131-9. doi: 10.1158/1078-0432.CCR-10-1220. Epub 2011 Jan 10. [Article]
- Bello CL, LaBadie RR, Ni G, Boutros T, McCormick C, Ndongo MN: The effect of dacomitinib (PF-00299804) on CYP2D6 activity in healthy volunteers who are extensive or intermediate metabolizers. Cancer Chemother Pharmacol. 2012 Apr;69(4):991-7. doi: 10.1007/s00280-011-1793-7. Epub 2011 Dec 7. [Article]
- Sepulveda JM, Sanchez-Gomez P, Vaz Salgado MA, Gargini R, Balana C: Dacomitinib: an investigational drug for the treatment of glioblastoma. Expert Opin Investig Drugs. 2018 Oct;27(10):823-829. doi: 10.1080/13543784.2018.1528225. Epub 2018 Oct 5. [Article]
- Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS: Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. doi: 10.1016/S1470-2045(17)30608-3. Epub 2017 Sep 25. [Article]
- Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS: Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005 Nov 10;353(19):2012-24. doi: 10.1056/NEJMoa051918. [Article]
- da Cunha Santos G, Shepherd FA, Tsao MS: EGFR mutations and lung cancer. Annu Rev Pathol. 2011;6:49-69. doi: 10.1146/annurev-pathol-011110-130206. [Article]
- Bethune G, Bethune D, Ridgway N, Xu Z: Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010 Mar;2(1):48-51. [Article]
- 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. [Article]
- Bethesda (2006). Drugs and Lactation Database. National Library of Medicine.
- FDA approval [Link]
- FDA news [Link]
- Pfizer Oncology Dacomitinib (PF-00299804) Fact Sheet [File]
- External Links
- KEGG Drug
- D09883
- PubChem Compound
- 11511120
- PubChem Substance
- 347828287
- ChemSpider
- 9685914
- BindingDB
- 112499
- 2058848
- ChEBI
- 132268
- ChEMBL
- CHEMBL2110732
- ZINC
- ZINC000072266312
- PDBe Ligand
- 1C9
- Wikipedia
- Dacomitinib
- PDB Entries
- 4i23 / 4i24
- FDA label
- Download (744 KB)
- MSDS
- Download (57.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Metastatic Non-Small Cell Lung Cancer 1 3 Completed Treatment Lung Cancer 1 3 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 1 3 Completed Treatment Non-small Cell Lung Cancer With EGFR-Activating Mutations 1 2 Active Not Recruiting Treatment EGFR Positive Non-small Cell Lung Cancer / NSCLC Stage IIIC / NSCLC, Recurrent / Stage IIIB Non-Small Cell Lung Cancer / Stage IV Non-small Cell Lung Cancer (NSCLC) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 15.576 MG Tablet, film coated Oral 31.153 MG Tablet, film coated Oral 46.729 MG Tablet Oral 15 mg Tablet Oral 30 mg Tablet Oral 45 mg Tablet, film coated Oral 15 mg/1 Tablet, film coated Oral 30 mg/1 Tablet, film coated Oral 45 mg/1 Tablet, film coated Oral Tablet, film coated Oral 15 mg Tablet, film coated Oral 30 mg Tablet, film coated Oral 45 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8623883 No 2014-01-07 2025-05-05 US US7772243 No 2010-08-10 2028-08-26 US US10603314 No 2020-03-31 2026-02-02 US US10596162 No 2020-03-24 2026-02-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 184-187 ºC Williams J., et al. (2014). Canc. Treatment Rev. 40, 917. boiling point (°C) 665.7 ºC at 760 mmHg 'MSDS' water solubility <1 mg/mL 'MSDS' logP 3.92 'MSDS' - Predicted Properties
Property Value Source Water Solubility 0.00874 mg/mL ALOGPS logP 4.88 ALOGPS logP 4.71 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 12.5 Chemaxon pKa (Strongest Basic) 8.55 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 79.38 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 129.91 m3·mol-1 Chemaxon Polarizability 49.06 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-1000900000-111dc0928806f1086f0c Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0103900000-88b1e6bd02e1d931dbd5 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-2105900000-d1d51bc9f539ab4bbcdf Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0296-1106900000-f79ca399cad79342d19a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0fka-7819500000-619b6593e155c275fa07 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9103600000-b4f47f96fb9dfbc02aff Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 214.83841 predictedDeepCCS 1.0 (2019) [M+H]+ 217.23398 predictedDeepCCS 1.0 (2019) [M+Na]+ 223.14651 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Fry DW, Bridges AJ, Denny WA, Doherty A, Greis KD, Hicks JL, Hook KE, Keller PR, Leopold WR, Loo JA, McNamara DJ, Nelson JM, Sherwood V, Smaill JB, Trumpp-Kallmeyer S, Dobrusin EM: Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):12022-7. [Article]
- Brzezniak C, Carter CA, Giaccone G: Dacomitinib, a new therapy for the treatment of non-small cell lung cancer. Expert Opin Pharmacother. 2013 Feb;14(2):247-53. doi: 10.1517/14656566.2013.758714. Epub 2013 Jan 7. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Coadministration of a single 45 mg oral dose of dacomitinib increased dextromethorphan (a CYP2D6 substrate) Cmax by 9.7-fold and AUClast by 9.6 fold.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Bello CL, LaBadie RR, Ni G, Boutros T, McCormick C, Ndongo MN: The effect of dacomitinib (PF-00299804) on CYP2D6 activity in healthy volunteers who are extensive or intermediate metabolizers. Cancer Chemother Pharmacol. 2012 Apr;69(4):991-7. doi: 10.1007/s00280-011-1793-7. Epub 2011 Dec 7. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Bethesda (2006). Drugs and Lactation Database. National Library of Medicine.
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Dacomatinib EMA label [Link]
Drug created at October 20, 2016 21:05 / Updated at February 08, 2023 20:46