Identification

Name
Dacomitinib
Accession Number
DB11963
Type
Small Molecule
Groups
Approved, Investigational
Description

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 model[1], although further investigations are needed.

Structure
Thumb
Synonyms
  • Dacomitinib
  • Dacomitinib anhydrous
  • Dacomitinibum
External IDs
PF-00299804
Product Ingredients
IngredientUNIICASInChI Key
Dacomitinib monohydrate5092U85G581042385-75-0BSPLGGCPNTZPIH-IPZCTEOASA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VizimproTablet, film coated45 mg/1OralPfizer Laboratories Div Pfizer Inc2018-10-04Not applicableUs
VizimproTablet, film coated15 mg/1OralPfizer Laboratories Div Pfizer Inc2018-10-04Not applicableUs
VizimproTablet, film coated15 mg/1OralU.S. Pharmaceuticals2018-11-01Not applicableUs
VizimproTablet, film coated30 mg/1OralPfizer Laboratories Div Pfizer Inc2018-10-04Not applicableUs
Categories
UNII
2XJX250C20
CAS number
1110813-31-4
Weight
Average: 469.939
Monoisotopic: 469.168080981
Chemical Formula
C24H25ClFN5O2
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

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]

Associated Conditions
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]

TargetActionsOrganism
AEpidermal growth factor receptor
inhibitor
Humans
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]

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]

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]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Dacomitinib can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Dacomitinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Dacomitinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Dacomitinib.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Dacomitinib.
5-androstenedioneThe metabolism of Dacomitinib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Dacomitinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Dacomitinib can be decreased when combined with 6-O-benzylguanine.
7-ethyl-10-hydroxycamptothecinThe metabolism of Dacomitinib can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Dacomitinib.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:28646172]
  2. 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. [PubMed:23294134]
  3. 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. [PubMed:18089823]
  4. 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. [PubMed:9751783]
  5. 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. [PubMed:21220471]
  6. 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. [PubMed:22147075]
  7. 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. [PubMed:30247945]
  8. 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. [PubMed:28958502]
  9. 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. [PubMed:16282176]
  10. 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. [PubMed:20887192]
  11. 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. [PubMed:22263017]
  12. 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. [PubMed:28648122]
  13. Bethesda (2006). Drugs and Lactation Database. National Library of Medicine.
  14. FDA approval [Link]
  15. FDA news [Link]
  16. Pfizer Oncology Dacomitinib (PF-00299804) Fact Sheet [File]
External Links
KEGG Drug
D09883
PubChem Compound
11511120
PubChem Substance
347828287
ChemSpider
9685914
BindingDB
112499
ChEBI
132268
ChEMBL
CHEMBL2110732
HET
1C9
Wikipedia
Dacomitinib
PDB Entries
4i23 / 4i24
FDA label
Download (744 KB)
MSDS
Download (57.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAdvanced Malignant Solid Tumors1
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers2
1CompletedBasic ScienceHealthy Volunteers / Otherwise Healthy Volunteers With Mild or Moderate Hepatic Dysfunction1
1CompletedTreatmentCarcinoma, Non-Small Cell / Neoplasms Metastasis1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentNeoplasms2
1CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1RecruitingBasic ScienceNeoplasms1
1TerminatedBasic ScienceLung Cancer Non-Small Cell Cancer (NSCLC)1
1TerminatedTreatmentAdenocarcinomas / Carcinoma, Large Cell / Non-Small Cell Lung Carcinoma (NSCLC) / Squamous Cell Carcinoma (SCC)1
1, 2CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
1, 2CompletedTreatmentOral Cavity Cancer1
1, 2RecruitingTreatmentColorectal Cancers1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentSkin Squamous Cell Cancer1
2CompletedTreatmentAdvanced Gastric Cancer / HER21
2CompletedTreatmentCarcinoma, Non-Small Cell1
2CompletedTreatmentGBM / Glioblastoma Multiforme (GBM) / Glioblastomas1
2CompletedTreatmentGlioblastomas / Recurrent Brain Tumors1
2CompletedTreatmentHead Neck Cancer Squamous Cell Metastatic / Head Neck Cancer Squamous Cell Recurrent1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
2CompletedTreatmentNeoplasms, Head and Neck1
2CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
2RecruitingTreatmentPenile Neoplasms / Squamous Cell Carcinoma (SCC)1
2TerminatedTreatmentBrain Cancer1
3Active Not RecruitingTreatmentEGFR Positive Non-small Cell Lung Cancer / Non-small Cell Lung Cancer With EGFR-Activating Mutations1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentLung Cancers1
Not AvailableCompletedDiagnosticHead and Neck Squamous Cell Carcinoma (HNSCC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral15 mg/1
Tablet, film coatedOral30 mg/1
Tablet, film coatedOral45 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)184-187 ºCWilliams 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'
logP3.92'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility0.00874 mg/mLALOGPS
logP4.88ALOGPS
logP4.71ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)12.5ChemAxon
pKa (Strongest Basic)8.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area79.38 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity129.91 m3·mol-1ChemAxon
Polarizability49.06 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Quinazolinamine / Methoxyaniline / Anisole / Aniline or substituted anilines / N-arylamide / Alkyl aryl ether / Chlorobenzene / Aminopyrimidine / Halobenzene / Fluorobenzene
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

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
  1. 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. [PubMed:9751783]
  2. 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. [PubMed:23294134]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. 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. [PubMed:22147075]
  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. [PubMed:28648122]
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
  1. 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. [PubMed:28648122]
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
  1. 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. [PubMed:28648122]
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
  1. Bethesda (2006). Drugs and Lactation Database. National Library of Medicine.

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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
Substrate
Inhibitor
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

Drug created on October 20, 2016 15:05 / Updated on December 16, 2018 06:59