Identification

Name
Vandetanib
Accession Number
DB05294  (DB08764)
Type
Small Molecule
Groups
Approved
Description

Vandetanib is an oral once-daily kinase inhibitor of tumour angiogenesis and tumour cell proliferation with the potential for use in a broad range of tumour types.

On April 6 2011, vandetanib was approved by the FDA to treat nonresectable, locally advanced, or metastatic medullary thyroid cancer in adult patients.

Structure
Thumb
Synonyms
  • N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-4-piperidinyl)methoxy)-4-quinazolinamine
  • N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
External IDs
GNF-PF-2188 / HSDB 8198 / ZD 6474 / ZD-6474 / ZD6474
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CaprelsaTablet100 mg/1OralAstraZeneca Pharmaceuticals LP2011-07-252020-05-31Us
CaprelsaTablet, film coated100 mgOralGenzyme Europe Bv2012-02-17Not applicableEu
CaprelsaTablet300 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2012-02-23Not applicableCanada
CaprelsaTablet, film coated100 mg/1OralGenzyme Corporation2011-07-25Not applicableUs
CaprelsaTablet300 mg/1OralAstraZeneca Pharmaceuticals LP2011-07-252020-05-31Us
CaprelsaTablet, film coated300 mgOralGenzyme Europe Bv2012-02-17Not applicableEu
CaprelsaTablet, film coated300 mg/1OralGenzyme Corporation2011-07-25Not applicableUs
CaprelsaTablet100 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2012-02-23Not applicableCanada
VandetanibTablet100 mg/1OralAstra Zeneca Lp2011-04-212013-06-22Us
VandetanibTablet300 mg/1OralAstra Zeneca Lp2011-04-212014-08-17Us
International/Other Brands
Zactima (AstraZeneca ) / Zictifa (AstraZeneca )
Categories
UNII
YO460OQ37K
CAS number
443913-73-3
Weight
Average: 475.354
Monoisotopic: 474.106666884
Chemical Formula
C22H24BrFN4O2
InChI Key
UHTHHESEBZOYNR-UHFFFAOYSA-N
InChI
InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)
IUPAC Name
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
SMILES
COC1=C(OCC2CCN(C)CC2)C=C2N=CN=C(NC3=C(F)C=C(Br)C=C3)C2=C1

Pharmacology

Indication

Vandetanib is currently approved as an alternative to local therapies for both unresectable and disseminated disease. Because Vandetanib can prolong the Q-T interval, it is contraindicated for use in patients with serious cardiac complications such as congenital long QT syndrome and uncompensated heart failure.

Associated Conditions
Pharmacodynamics

Mean IC50 of approximately 2.1 μg/mL.

Mechanism of action

ZD-6474 is a potent and selective inhibitor of VEGFR (vascular endothelial growth factor receptor), EGFR (epidermal growth factor receptor) and RET (REarranged during Transfection) tyrosine kinases.

VEGFR- and EGFR-dependent signalling are both clinically validated pathways in cancer, including non-small-cell lung cancer (NSCLC). RET activity is important in some types of thyroid cancer, and early data with vandetanib in medullary thyroid cancer has led to orphan-drug designation by the regulatory authorities in the USA and EU.

TargetActionsOrganism
UVascular endothelial growth factor A
inhibitor
Human
UEpidermal growth factor receptor
inhibitor
Human
UProtein-tyrosine kinase 6
inhibitor
Human
UAngiopoietin-1 receptor
inhibitor
Human
UProto-oncogene tyrosine-protein kinase receptor RetNot AvailableHuman
Absorption

Slow- peak plasma concentrations reached at a median 6 hours. On multiple dosing, Vandetanib accumulates about 8 fold with steady state reached after around 3 months.

Volume of distribution

Vd of about 7450 L.

Protein binding

Protein binding of about 90%.

Metabolism

Unchanged vandentanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and feces. N-desmethyl-vandetanib is primarily produced by CYP3A4, and vandetanib-N-oxide is primarily produced by flavin–containing monooxygenase enzymes FMO1 and FMO3.

Route of elimination

About 69% was recovered following 21 days after a single dose of vandentanib. 44% was found in feces and 25% in urine.

Half life

Median half life of 19 days.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Vandetanib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Vandetanib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Vandetanib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Vandetanib.
5-androstenedioneThe metabolism of Vandetanib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Vandetanib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Vandetanib.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Vandetanib.
AbemaciclibVandetanib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AbexinostatThe risk or severity of QTc prolongation can be increased when Abexinostat is combined with Vandetanib.
Food Interactions
Not Available

References

General References
  1. Bates D: ZD-6474. AstraZeneca. Curr Opin Investig Drugs. 2003 Dec;4(12):1468-72. [PubMed:14763134]
  2. Ton GN, Banaszynski ME, Kolesar JM: Vandetanib: a novel targeted therapy for the treatment of metastatic or locally advanced medullary thyroid cancer. Am J Health Syst Pharm. 2013 May 15;70(10):849-55. doi: 10.2146/ajhp120253. [PubMed:23640345]
  3. Andriamanana I, Gana I, Duretz B, Hulin A: Simultaneous analysis of anticancer agents bortezomib, imatinib, nilotinib, dasatinib, erlotinib, lapatinib, sorafenib, sunitinib and vandetanib in human plasma using LC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 May 1;926:83-91. doi: 10.1016/j.jchromb.2013.01.037. Epub 2013 Mar 16. [PubMed:23562906]
External Links
KEGG Drug
D06407
PubChem Compound
3081361
PubChem Substance
175426969
ChemSpider
2338979
BindingDB
21
ChEBI
49960
ChEMBL
CHEMBL24828
PharmGKB
PA166118341
HET
ZD6
Wikipedia
Vandetanib
ATC Codes
L01XE12 — Vandetanib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
2ivu
FDA label
Download (220 KB)
MSDS
Download (220 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Malignancies1
1CompletedBasic Science(t1/2,λz) / Cmax / Pharmacokinetics / Plasma [AUC(0-672)] / Plasma [AUC(0-t)] / Plasma AUC / Tmax1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedTreatmentAdenocarcinomas / Colorectal / Metastatic1
1CompletedTreatmentAdvanced Colorectal Carcinoma1
1CompletedTreatmentAdvanced Incurable Solid Malignancy1
1CompletedTreatmentAdvanced Solid, Malignant Tumors1
1CompletedTreatmentAnal, Colon, and Rectal Cancers / Colon/Rectal Cancer / Neoplasms, Colorectal1
1CompletedTreatmentBiliary Cancer / Malignant Neoplasm of Pancreas / Malignant Solid Tumours1
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentCarcinoma NOS / Lung Cancers / Non-Small Cell Lung1
1CompletedTreatmentColorectal Cancers2
1CompletedTreatmentDiffuse Intrinsic Pontine Glioma (DIPG)1
1CompletedTreatmentGlioblastomas1
1CompletedTreatmentGlioblastomas / Gliosarcoma2
1CompletedTreatmentHead and Neck Carcinoma1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentLung Cancers / Lymphoproliferative Disorders / Malignant Lymphomas / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignant Gliomas1
1CompletedTreatmentMalignant Gliomas / Progressive Low-Grade Gliomas / Recurrent High-Grade Gliomas1
1CompletedTreatmentMalignant Neoplasm of Pancreas1
1CompletedTreatmentMetastatic Breast Cancer (MBC)1
1RecruitingTreatmentAdvanced Cancers1
1TerminatedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Esophageal Cancers1
1TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1TerminatedTreatmentNeuroblastomas1
1Unknown StatusTreatmentCancer of the Esophagus, Gastroesophageal Junction or Stomach1
1WithdrawnTreatmentCancer, Breast / Head and Neck Carcinoma / Lung Cancers / Prostate Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1WithdrawnTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
1WithdrawnTreatmentParaganglioma / Phaeochromocytoma1
1WithdrawnTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2Active Not RecruitingTreatmentGlioblastoma Multiforme (GBM) / Gliosarcoma1
1, 2Active Not RecruitingTreatmentMedullary Thyroid Cancer (MTC) / Multiple Endocrine Neoplasia Type 2a / Multiple Endocrine Neoplasia Type 2B1
1, 2CompletedTreatmentUnresectable Locally Advanced or Metastatic, Medullary Thyroid Carcinoma1
1, 2RecruitingTreatmentHereditary Leiomyomatosis and Renal Cell Cancer / Papillary Renal Cell Carcinoma, Sporadic / Renal Cell Adenocarcinoma1
1, 2TerminatedTreatmentCancer of the Ovary1
1, 2TerminatedTreatmentMedullary Thyroid Cancer (MTC)1
2Active Not RecruitingPreventionLip and Oral Cavity Squamous Cell Carcinoma / Oral Cavity Verrucous Carcinoma / Precancerous Conditions1
2Active Not RecruitingTreatmentGIST1
2Active Not RecruitingTreatmentNeoplasms, Thyroid1
2CompletedTreatmentAdvanced Breast Cancer1
2CompletedTreatmentAmpullary Carcinoma / Biliary Tract Cancer / Cancer Of The Extrahepatic Bile Duct / Gallbladder Cancer1
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Mixed Oligoastrocytoma / Anaplastic Oligodendroglioma (AO) / Glioblastoma Multiforme (GBM) / Gliosarcoma1
2CompletedTreatmentBladder Cancers / Transitional Cell Carcinoma1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentColorectal / Malignancies1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentHormone Refractory / Metastatic / Prostate Cancer1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)4
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2CompletedTreatmentLung Cancers2
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentNeoplasm Metastases / Neoplasms, Breast1
2CompletedTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentNon-Small Cell Lung Cancer (NSCLC, Locally Advanced or Metastatic, Second-line1
2CompletedTreatmentProstate Cancer2
2CompletedTreatmentRenal Cancers / Von Hippel Lindau1
2CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2CompletedTreatmentThyroid Cancers2
2RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Follicular Thyroid Cancer / Poorly Differentiated Thyroid Gland Carcinoma / Thyroid Cancer, Medullary / Thyroid Cancers / Thyroid Papillary Carcinoma1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
2RecruitingTreatmentNeoplasms1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2SuspendedTreatmentBreast Cancer Invasive Nos1
2TerminatedTreatmentAbdominal wall neoplasm / Fallopian Tube Neoplasms / Neoplasms, Ovarian1
2TerminatedTreatmentAdvanced Clear Cell Renal Carcinoma1
2TerminatedTreatmentCancer, Breast2
2TerminatedTreatmentHead and Neck Carcinoma1
2TerminatedTreatmentLung Cancers2
2TerminatedTreatmentLung Cancers / Pleural Effusions1
2TerminatedTreatmentMalignant Neoplasm of Stomach1
2TerminatedTreatmentMesothelioma1
2TerminatedTreatmentProstate Cancer1
2Unknown StatusTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Ureteral Cancer / Urethral Cancer1
2Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
2WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Active Not RecruitingTreatmentDifferentiated Thyroid Cancer (DTC)1
3Active Not RecruitingTreatmentLocally Advanced or Metastatic Medullary Thyroid Cancer / Medullary Thyroid Cancer (MTC)1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
3Active Not RecruitingTreatmentThyroid Cancers1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
4Active Not RecruitingTreatmentThyroid Cancers1
Not AvailableCompletedNot AvailableAll Belgian Patients With Aggressive, Symptomatic Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer and Taking Caprelsa® Will be Included1
Not AvailableRecruitingNot AvailableAdvanced/Metastatic Medullary Thyroid Cancer (MTC) / Symptomatic, Aggressive, Sporadic, Unresectable, Locally1
Not AvailableRecruitingDiagnosticHigh-Grade Gliomas / Malignancies1
Not AvailableRecruitingTreatmentGastrointestinal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral300 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral300 mg
TabletOral100 mg/1
TabletOral300 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8642608No2014-02-042022-02-06Us
US8067427No2011-11-292028-08-08Us
US7173038No2007-02-062021-08-14Us
USRE42353No2011-05-102017-09-23Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.008 mg/mL at 25°C (77°F )FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.0102 mg/mLALOGPS
logP5.01ALOGPS
logP4.54ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)13.8ChemAxon
pKa (Strongest Basic)9.13ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.51 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity118.63 m3·mol-1ChemAxon
Polarizability47.1 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9961
Blood Brain Barrier+0.9596
Caco-2 permeable+0.611
P-glycoprotein substrateSubstrate0.7412
P-glycoprotein inhibitor IInhibitor0.7327
P-glycoprotein inhibitor IIInhibitor0.9501
Renal organic cation transporterInhibitor0.6556
CYP450 2C9 substrateNon-substrate0.8419
CYP450 2D6 substrateNon-substrate0.5827
CYP450 3A4 substrateSubstrate0.6006
CYP450 1A2 substrateInhibitor0.7333
CYP450 2C9 inhibitorNon-inhibitor0.7749
CYP450 2D6 inhibitorInhibitor0.5867
CYP450 2C19 inhibitorInhibitor0.5077
CYP450 3A4 inhibitorInhibitor0.5288
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8009
Ames testAMES toxic0.5693
CarcinogenicityNon-carcinogens0.9322
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.8342
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (103 KB)
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0293000000-9037b32a179af5e7ba9a

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
Aniline and substituted anilines / Anisoles / Alkyl aryl ethers / Aminopyrimidines and derivatives / Bromobenzenes / Fluorobenzenes / Piperidines / Aryl bromides / Imidolactams / Aryl fluorides
show 8 more
Substituents
Quinazolinamine / Anisole / Aniline or substituted anilines / Alkyl aryl ether / Aminopyrimidine / Bromobenzene / Fluorobenzene / Halobenzene / Aryl bromide / Aryl fluoride
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, organofluorine compound, organobromine compound, aromatic ether, secondary amine, quinazolines (CHEBI:49960)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor receptor binding
Specific Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
Molecular Weight
27042.205 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Link [Link]
Details
3. Protein-tyrosine kinase 6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. F...
Gene Name
PTK6
Uniprot ID
Q13882
Uniprot Name
Protein-tyrosine kinase 6
Molecular Weight
51833.72 Da
References
  1. Link [Link]
Details
4. Angiopoietin-1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading...
Gene Name
TEK
Uniprot ID
Q02763
Uniprot Name
Angiopoietin-1 receptor
Molecular Weight
125829.005 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadp binding
Specific Function
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
Molecular Weight
60310.285 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine monooxygenase activity
Specific Function
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Molecular Weight
60032.975 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Link [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Link [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Link [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [PubMed:19390592]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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
References
  1. Zheng LS, Wang F, Li YH, Zhang X, Chen LM, Liang YJ, Dai CL, Yan YY, Tao LY, Mi YJ, Yang AK, To KK, Fu LW: Vandetanib (Zactima, ZD6474) antagonizes ABCC1- and ABCG2-mediated multidrug resistance by inhibition of their transport function. PLoS One. 2009;4(4):e5172. doi: 10.1371/journal.pone.0005172. Epub 2009 Apr 23. [PubMed:19390592]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Shen H, Yang Z, Zhao W, Zhang Y, Rodrigues AD: Assessment of vandetanib as an inhibitor of various human renal transporters: inhibition of multidrug and toxin extrusion as a possible mechanism leading to decreased cisplatin and creatinine clearance. Drug Metab Dispos. 2013 Dec;41(12):2095-103. doi: 10.1124/dmd.113.053215. Epub 2013 Sep 11. [PubMed:24026623]

Drug created on November 18, 2007 11:23 / Updated on December 11, 2018 12:57