Identification

Name
Ezogabine
Accession Number
DB04953
Type
Small Molecule
Groups
Approved
Description

Ezogabine (D23129) is a close structural analog of the centrally acting analgesic flupitrine. It is a neuronal potassium channel opener being developed as a first-in-class antiepileptic drug (AED) and is currently being studied in Phase 3 trials as an adjunctive treatment for partial-onset seizures in adult patients with refractory epilepsy. FDA approved in June 10, 2011 under the name of ezogabine.

Structure
Thumb
Synonyms
  • Ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate
  • Ethyl 2-amino-4-((P-fluorobenzyl)amino)carbanilate
  • EZG
  • N-(2-Amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester
  • N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester
  • Retigabine
  • RTG
External IDs
D-23129 / D23129
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PotigaTablet, film coated400 mg/1OralGlaxosmithkline Inc2012-04-192019-06-30Us
PotigaTablet, film coated50 mg/1OralGlaxosmithkline Inc2012-04-192019-07-31Us
PotigaTablet, film coated300 mg/1OralGlaxosmithkline Inc2012-04-192018-08-31Us
PotigaTablet, film coated200 mg/1OralGlaxosmithkline Inc2012-04-192019-07-31Us
TrobaltTablet, film coated50 mgOralGlaxo Group Limited2011-03-28Not applicableEu
TrobaltTablet, film coated400 mgOralGlaxo Group Limited2011-03-28Not applicableEu
TrobaltTablet, film coated200 mgOralGlaxo Group Limited2011-03-28Not applicableEu
TrobaltTablet, film coated100 mgOralGlaxo Group Limited2011-03-28Not applicableEu
TrobaltTablet, film coated300 mgOralGlaxo Group Limited2011-03-28Not applicableEu
TrobaltTablet, film coated200 mgOralGlaxo Group Limited2011-03-28Not applicableEu
International/Other Brands
Potiga
Categories
UNII
12G01I6BBU
CAS number
150812-12-7
Weight
Average: 303.3314
Monoisotopic: 303.13830504
Chemical Formula
C16H18FN3O2
InChI Key
PCOBBVZJEWWZFR-UHFFFAOYSA-N
InChI
InChI=1S/C16H18FN3O2/c1-2-22-16(21)20-15-8-7-13(9-14(15)18)19-10-11-3-5-12(17)6-4-11/h3-9,19H,2,10,18H2,1H3,(H,20,21)
IUPAC Name
ethyl N-(2-amino-4-{[(4-fluorophenyl)methyl]amino}phenyl)carbamate
SMILES
CCOC(=O)NC1=C(N)C=C(NCC2=CC=C(F)C=C2)C=C1

Pharmacology

Indication

Adjuvant treatment of partial-onset seizures.

Structured Indications
Pharmacodynamics

As compared to other antiepileptic agents, ezogabine is unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects. The antiepileptics, as a drug class, are routinely used in the treatment of a number of disease states in addition to epilepsy. Ezogabine is highly efficacious in a broad-spectrum of in vivo epilepsy and seizure models. A comparison of antiepileptic form activity of ezogabine with that of conventional anticonvulsants in in vitro models suggests that retigabine is especially likely to be useful in the treatment of pharmacoresistant epilepsy. Retigabine clearly attenuates pain-like behaviors in various animal models of neuropathic pain; it may also prove to be useful in treatment of clinical anxiety disorders. Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.

Mechanism of action

Ezogabine has a novel mechanism of action that involves opening of neuronal Kv7.2-7.5 (formerly KCNQ2-5) voltage activated potassium channels. These channels (primarily Kv7.2/7.3) enable generation of the M-current, a sub-threshold potassium current that serves to stabilize the membrane potential and control neuronal excitability. In addition to acting on potassium ion channels, retigabine also affects GABA neurotransmission in the GABA-A receptor, which is a key inhibitory receptor in the central nervous system and is implicated in epilepsy. Malfunctioning of the GABA-A receptor leads to hyperexcitability in the brain, which causes seizures, making this receptor an important target for antiepileptic therapeutics. Apart from increasing the concentration of GABA in the brain (by either enhancing GABA synthesis or blocking GABA metabolism), retigabine allosterically potentiates GABA-induced current in rat cortical neurons in a concentration-dependent manner. Numerous studies have demonstrated that retigabine is effective in a broad spectrum of in vivo epilepsy and seizure models.

TargetActionsOrganism
UPotassium voltage-gated channel subfamily KQT member 2Not AvailableHuman
UPotassium voltage-gated channel subfamily KQT member 3Not AvailableHuman
UPotassium voltage-gated channel subfamily KQT member 4Not AvailableHuman
UPotassium voltage-gated channel subfamily KQT member 5Not AvailableHuman
Absorption

Rapidly absorbed and distributed, with an absolute oral bioavailability of 60%. Pharmacokinetics of ezogabine suggest first-order kinetics. Tmax, single oral dose = 30-120 minutes; Time to steady state = 3 days

Volume of distribution

8.7 L/kg

Protein binding

Approximately 80% protein bound.

Metabolism

Ezogabine is metabolized exclusively via phase II hepatic N-glucurodination and acetylation. N-glucurodination is the major metabolic pathway of the two and form two major N-glucuronide metabolites. The enzymes involved are UGT1A1, 1A9, 1A4, and 1A3. However, the product of the N-acetyl pathway is a weak, active metabolite referred to as NAMR. The enzyme that is involved in the N-acetyl pathway is called N-acetyltransferase 2. The pharmacokinetics of NAMR and ezogabine are similar. The cytochrome P450 enzyme system is not involved with the metabolism of ezogabine.

Route of elimination

Urine (85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR) and feces (14%, 3% of total dose as unchanged drug)

Half life

Terminal half-life = 7.5 hours

Clearance

0.58 - 0.76 L/h·kg. Clearance may differ between ethnic groups with Black Americans having 20% lower clearance than Caucasian Americans.

Toxicity

Lethal Dose, acute, oral, rat = 100 mg/kg; Lethal Dose, chronic, oral, rat = 5.1 mg/kg/day, 90-day; Most common adverse effects that lead to discontinuation of therapy include dizziness and somnolence.

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

Interactions

Drug Interactions
DrugInteractionDrug group
ArtesunateThe serum concentration of the active metabolites of Artesunate can be reduced when Artesunate is used in combination with Ezogabine resulting in a loss in efficacy.Approved, Investigational
CarbamazepineThe serum concentration of Ezogabine can be decreased when it is combined with Carbamazepine.Approved, Investigational
DoxofyllineThe serum concentration of Doxofylline can be decreased when it is combined with Ezogabine.Approved, Investigational
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Ezogabine.Approved
LamotrigineThe serum concentration of Lamotrigine can be decreased when it is combined with Ezogabine.Approved, Investigational
MefloquineThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mefloquine.Approved
MianserinThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Mianserin.Approved, Investigational
OrlistatThe serum concentration of Ezogabine can be decreased when it is combined with Orlistat.Approved, Investigational
PregabalinThe therapeutic efficacy of Ezogabine can be decreased when used in combination with Pregabalin.Approved, Illicit, Investigational
Food Interactions
  • With a high-fat meal, Cmax is moderately increased.

References

General References
  1. Porter RJ, Nohria V, Rundfeldt C: Retigabine. Neurotherapeutics. 2007 Jan;4(1):149-54. [PubMed:17199031]
  2. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70. [PubMed:12545144]
  3. Hermann R, Knebel NG, Niebch G, Richards L, Borlak J, Locher M: Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Eur J Clin Pharmacol. 2003 Apr;58(12):795-802. Epub 2003 Feb 28. [PubMed:12698305]
  4. Dost R, Rostock A, Rundfeldt C: The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation. Naunyn Schmiedebergs Arch Pharmacol. 2004 Apr;369(4):382-90. Epub 2004 Mar 9. [PubMed:15007538]
  5. Mikkelsen JD: The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat. Neurosci Lett. 2004 May 27;362(3):240-3. [PubMed:15158023]
  6. Punke MA, Friederich P: Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine. Anesthesiology. 2004 Aug;101(2):430-8. [PubMed:15277926]
  7. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20. [PubMed:15662042]
  8. Fatope MO: Retigabine (ASTA Medica). IDrugs. 2001 Jan;4(1):93-8. [PubMed:16034707]
  9. Orhan G, Wuttke TV, Nies AT, Schwab M, Lerche H: Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data. Expert Opin Pharmacother. 2012 Aug;13(12):1807-16. doi: 10.1517/14656566.2012.706278. Epub 2012 Jul 12. [PubMed:22783830]
  10. Amabile CM, Vasudevan A: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Pharmacotherapy. 2013 Feb;33(2):187-94. doi: 10.1002/phar.1185. [PubMed:23386597]
External Links
KEGG Drug
D09569
KEGG Compound
C13826
PubChem Compound
121892
PubChem Substance
175426917
ChemSpider
108740
BindingDB
50143558
ChEBI
68584
ChEMBL
CHEMBL41355
PharmGKB
PA144997862
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Retigabine
ATC Codes
N03AX21 — Retigabine
FDA label
Download (516 KB)
MSDS
Download (132 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceEpilepsies1
1CompletedTreatmentEpilepsies2
1WithdrawnNot AvailableEpilepsy, Localization Related1
2CompletedTreatmentDepression / Major Depressive Disorder (MDD)1
2CompletedTreatmentPostherpetic Neuralgia1
2RecruitingOtherAnhedonia / Depressive Disorders1
2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2TerminatedTreatmentEpilepsies1
3Active Not RecruitingTreatmentEpilepsies1
3CompletedBasic ScienceEpilepsies1
3CompletedTreatmentEpilepsies4
3CompletedTreatmentPartial onset seizure Epilepsy / Seizures1
3CompletedTreatmentPartial onset seizure Epilepsy1
3TerminatedTreatmentEpilepsies2
4CompletedPreventionHealth1
4TerminatedTreatmentEpilepsies1
4TerminatedTreatmentSeizures1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableEpilepsies2
Not AvailableCompletedNot AvailableEpilepsy, Localization Related1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral100 mg
Tablet, film coatedOral200 mg
Tablet, film coatedOral300 mg
Tablet, film coatedOral400 mg
Tablet, film coatedOral50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
pKa10.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0307 mg/mLALOGPS
logP3.07ALOGPS
logP2.7ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)3.99ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area76.38 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.02 m3·mol-1ChemAxon
Polarizability31.97 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9876
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5245
P-glycoprotein substrateNon-substrate0.5295
P-glycoprotein inhibitor INon-inhibitor0.6642
P-glycoprotein inhibitor IINon-inhibitor0.9155
Renal organic cation transporterNon-inhibitor0.8998
CYP450 2C9 substrateNon-substrate0.8602
CYP450 2D6 substrateNon-substrate0.8045
CYP450 3A4 substrateNon-substrate0.679
CYP450 1A2 substrateInhibitor0.8417
CYP450 2C9 inhibitorNon-inhibitor0.607
CYP450 2D6 inhibitorInhibitor0.5995
CYP450 2C19 inhibitorNon-inhibitor0.5221
CYP450 3A4 inhibitorInhibitor0.5085
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6414
Ames testNon AMES toxic0.5119
CarcinogenicityNon-carcinogens0.621
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4793 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9807
hERG inhibition (predictor II)Non-inhibitor0.6007
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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 phenylbenzamines. These are aromatic compounds consisting of a benzyl group that is N-linked to a benzamine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylmethylamines
Direct Parent
Phenylbenzamines
Alternative Parents
Phenylalkylamines / Benzylamines / Aniline and substituted anilines / Secondary alkylarylamines / Fluorobenzenes / Aryl fluorides / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids and derivatives / Primary amines / Organopnictogen compounds
show 3 more
Substituents
Phenylbenzamine / Benzylamine / Aniline or substituted anilines / Phenylalkylamine / Fluorobenzene / Halobenzene / Secondary aliphatic/aromatic amine / Aralkylamine / Aryl fluoride / Aryl halide
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organofluorine compound, carbamate ester, substituted aniline, secondary amino compound (CHEBI:68584)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated potassium channel activity
Specific Function
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current...
Gene Name
KCNQ2
Uniprot ID
O43526
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 2
Molecular Weight
95846.575 Da
References
  1. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H: The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol. 2005 Apr;67(4):1009-17. Epub 2005 Jan 20. [PubMed:15662042]
  2. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917]
  3. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683]
  4. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. [PubMed:10908292]
  5. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. [PubMed:10953053]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated potassium channel activity
Specific Function
Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native ...
Gene Name
KCNQ3
Uniprot ID
O43525
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 3
Molecular Weight
96741.515 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917]
  2. Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed:17456683]
  3. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA: Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol. 2000 Aug;58(2):253-62. [PubMed:10908292]
  4. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK: Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600. [PubMed:10953053]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Potassium channel activity
Specific Function
Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked b...
Gene Name
KCNQ4
Uniprot ID
P56696
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 4
Molecular Weight
77099.99 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917]
  2. Schroder RL, Jespersen T, Christophersen P, Strobaek D, Jensen BS, Olesen SP: KCNQ4 channel activation by BMS-204352 and retigabine. Neuropharmacology. 2001 Jun;40(7):888-98. [PubMed:11378159]
  3. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006 Jun;55(6):711-21. [PubMed:16713428]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated potassium channel activity
Specific Function
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium ...
Gene Name
KCNQ5
Uniprot ID
Q9NR82
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 5
Molecular Weight
102178.015 Da
References
  1. Hirano K, Kuratani K, Fujiyoshi M, Tashiro N, Hayashi E, Kinoshita M: Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice. Neurosci Lett. 2007 Feb 14;413(2):159-62. Epub 2006 Dec 20. [PubMed:17184917]
  2. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J, Richards L, Cnota HP, Troy S: Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther. 2003 Jan;73(1):61-70. [PubMed:12545144]
  3. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006 Jun;55(6):711-21. [PubMed:16713428]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490]
  2. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R: N-Glucuronidation of the antiepileptic drug retigabine: results from studies with human volunteers, heterologously expressed human UGTs, human liver, kidney, and liver microsomal membranes of Crigler-Najjar type II. Metabolism. 2006 Jun;55(6):711-21. [PubMed:16713428]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
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
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T: Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12. [PubMed:10220490]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Orhan G, Wuttke TV, Nies AT, Schwab M, Lerche H: Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data. Expert Opin Pharmacother. 2012 Aug;13(12):1807-16. doi: 10.1517/14656566.2012.706278. Epub 2012 Jul 12. [PubMed:22783830]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Arylamine n-acetyltransferase activity
Specific Function
Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivat...
Gene Name
NAT2
Uniprot ID
P11245
Uniprot Name
Arylamine N-acetyltransferase 2
Molecular Weight
33542.235 Da
References
  1. Amabile CM, Vasudevan A: Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures. Pharmacotherapy. 2013 Feb;33(2):187-94. doi: 10.1002/phar.1185. [PubMed:23386597]

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 15:34