Ezogabine

Identification

Summary

Ezogabine is an antiepileptic agent used as an adjuvant treatment of partial-onset seizures.

Generic Name
Ezogabine
DrugBank Accession Number
DB04953
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 303.3314
Monoisotopic: 303.13830504
Chemical Formula
C16H18FN3O2
Synonyms
  • ethyl {2-amino-4-[(4-fluorobenzyl)amino]phenyl}carbamate
  • Ethyl 2-amino-4-((p-fluorobenzyl)amino)carbanilate
  • EZG
  • Ezogabine
  • N-(2-Amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester
  • N-(2-Amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester
  • Retigabina
  • Retigabine
  • RTG
External IDs
  • AWD-21360
  • AWD21-360
  • D-23129
  • D23129
  • GKE-841
  • GW-582892X
  • GW582892X
  • WAY-143841

Pharmacology

Indication

Adjuvant treatment of partial-onset seizures.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofRefractory partial onset seizure•••••••••••••••••
Contraindications & Blackbox Warnings
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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 AvailableHumans
UPotassium voltage-gated channel subfamily KQT member 3Not AvailableHumans
UPotassium voltage-gated channel subfamily KQT member 4Not AvailableHumans
UPotassium voltage-gated channel subfamily KQT member 5Not AvailableHumans
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.

Adverse Effects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Ezogabine is combined with 1,2-Benzodiazepine.
AbacavirAbacavir may decrease the excretion rate of Ezogabine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Ezogabine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ezogabine which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Ezogabine which could result in a higher serum level.
Food Interactions
  • Take with or without food. High-fat meals alter drug absorption, but not to a clinically significant extent.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PotigaTablet, film coated200 mg/1OralGlaxoSmithKline LLC2012-04-192019-07-31US flag
PotigaTablet, film coated400 mg/1OralGlaxoSmithKline LLC2012-04-192019-06-30US flag
PotigaTablet, film coated50 mg/1OralGlaxoSmithKline LLC2012-04-192019-07-31US flag
PotigaTablet, film coated300 mg/1OralGlaxoSmithKline LLC2012-04-192018-08-31US flag
TrobaltTablet, film coated400 mgOralGlaxo Group Limited2016-09-082018-11-19EU flag

Categories

ATC Codes
N03AX21 — Retigabine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Amine / Aniline or substituted anilines / Aralkylamine / Aromatic homomonocyclic compound / Aryl fluoride / Aryl halide / Benzylamine / Carboximidic acid derivative / Fluorobenzene / Halobenzene
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organofluorine compound, carbamate ester, substituted aniline, secondary amino compound (CHEBI:68584)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
12G01I6BBU
CAS number
150812-12-7
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

References

General References
  1. Porter RJ, Nohria V, Rundfeldt C: Retigabine. Neurotherapeutics. 2007 Jan;4(1):149-54. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Punke MA, Friederich P: Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine. Anesthesiology. 2004 Aug;101(2):430-8. [Article]
  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. [Article]
  8. Fatope MO: Retigabine (ASTA Medica). IDrugs. 2001 Jan;4(1):93-8. [Article]
  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. [Article]
  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. [Article]
KEGG Drug
D09569
KEGG Compound
C13826
PubChem Compound
121892
PubChem Substance
175426917
ChemSpider
108740
BindingDB
50143558
RxNav
1112990
ChEBI
68584
ChEMBL
CHEMBL41355
ZINC
ZINC000000016154
PharmGKB
PA144997862
PDBe Ligand
FBX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Retigabine
PDB Entries
7bym / 7cr2 / 7cr7
FDA label
Download (516 KB)
MSDS
Download (132 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedTreatmentEpilepsy1
4TerminatedTreatmentSeizures1
3CompletedBasic ScienceEpilepsy1
3CompletedTreatmentEpilepsy4
3CompletedTreatmentSeizures2

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/100MG
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/MSsplash10-0f89-0096000000-55fff99281eb03ec7868
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000w-6091000000-240f53405b19f9c732cd
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pc0-0193000000-ab3f244a41d928f6fdbd
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0036-4090000000-88ce3d7bde1c43f340c5
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0952000000-de014d114a0ad1d7e2d5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9320000000-bf946f1d62ec54bb66b1
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-175.40086
predicted
DeepCCS 1.0 (2019)
[M+H]+177.75887
predicted
DeepCCS 1.0 (2019)
[M+Na]+183.852
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51