Quinidine

Identification

Summary

Quinidine is a medication used to restore normal sinus rhythm, treat atrial fibrillation and flutter, and treat ventricular arrhythmias.

Brand Names
Nuedexta
Generic Name
Quinidine
DrugBank Accession Number
DB00908
Background

Quinidine is a D-isomer of quinine present in the bark of the Cinchona tree and similar plant species. This alkaloid was first described in 1848 and has a long history as an antiarrhythmic medication.1,2 Quinidine is considered the first antiarrhythmic drug (class Ia) and is moderately efficacious in the acute conversion of atrial fibrillation to normal sinus rhythm.1 It prolongs cellular action potential by blocking sodium and potassium currents. A phenomenon known as “quinidine syncope” was first described in the 1950s, characterized by syncopal attacks and ventricular fibrillation in patients treated with this drug.1 Due to its side effects and increased risk of mortality, the use of quinidine was reduced over the next few decades. However, it continues to be used in the treatment of Brugada syndrome, short QT syndrome and idiopathic ventricular fibrillation.2

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 324.4168
Monoisotopic: 324.183778022
Chemical Formula
C20H24N2O2
Synonyms
  • (+)-quinidine
  • (8R,9S)-Quinidine
  • (R)-(6-Methoxyquinolin-4-yl)((3S,4R,7S)-3-vinylquinuclidin-7-yl)methanol
  • (S)-(6-Methoxy-quinolin-4-yl)-((2R,5R)-5-vinyl-1-aza-bicyclo[2.2.2]oct-2-yl)-methanol
  • (S)-(6-Methoxyquinolin-4-yl)((2R,5R)-5-vinylquinuclidin-2-yl)methanol
  • 6-methoxy-α-(5-vinyl-2-quinuclidinyl)-4-quinolinemethanol
  • beta-Quinine
  • Chinidin
  • Chinidinum
  • CIN-QUIN
  • Conchinin
  • Conquinine
  • Pitayine
  • Quinidina
  • α-(6-methoxy-4-quinolyl)-5-vinyl-2-quinuclidinemethanol
  • β-quinine

Pharmacology

Indication

Quinidine is indicated for the management and prophylactic therapy of atrial fibrillation/flutter, as well as the suppression of recurrent documented ventricular arrhythmias.5,6 It is also used in the treatment of Brugada syndrome, short QT syndrome and idiopathic ventricular fibrillation.2,3.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMalaria caused by plasmodium falciparum••••••••••••
Used in combination to treatPseudobulbar affectCombination Product in combination with: Dextromethorphan (DB00514)••••••••••••
Management ofVentricular arrhythmias••••••••••••
Management ofAtrial flutter/fibrillation••••••••••••
Prophylaxis ofAtrial flutter/fibrillation••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Quinidine is an antimalarial schizonticide, and a class Ia antiarrhythmic agent used to interrupt or prevent reentrant arrhythmias and arrhythmias due to increased automaticity, such as atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia.6 In most patients, quinidine can lead to an increase in the sinus rate. Quinidine also causes a marked prolongation of the QT interval in a dose-related manner,1,5 acts peripherally as an α-adrenergic antagonist, and has anticholinergic and negative inotropic activity.6

The QT interval prolongation caused by quinidine can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such as torsades de pointes. The risk of torsades is increased by bradycardia, hypokalemia, hypomagnesemia or high serum levels of quinidine. However, this type of rhythm disturbance may appear in the absence of any of them.5,6 Patients treated with quinidine may also be at risk of a paradoxical increase in ventricular rate in atrial flutter/fibrillation, and patients with sick sinus syndrome treated with quinidine may develop marked sinus node depression and bradycardia.5,6

Mechanism of action

Quinidine has a complex electrophysiological profile that has not been fully elucidated. The antiarrhythmic actions of this drug are mediated through effects on sodium channels in Purkinje fibers. Quinidine blocks the rapid sodium channel (INa), decreasing the phase zero of rapid depolarization of the action potential.2 Quinidine also reduces repolarizing K+ currents (IKr, IKs), the inward rectifier potassium current (IK1), and the transient outward potassium current Ito, as well as the L-type calcium current ICa and the late INa inward current.2 The reduction of these currents leads to the prolongation of the action potential duration. By shortening the plateau but prolonging late depolarization, quinidine facilitates the formation of early afterdepolarisation (EAD).2 Additionally, in patients with malaria, quinidine acts primarily as an intra-erythrocytic schizonticide, and is gametocidal to Plasmodium vivax and P. malariae, but not to P. falciparum.5,6

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Humans
UPotassium channel subfamily K member 1
inhibitor
Humans
UPotassium channel subfamily K member 6
inhibitor
Humans
UVoltage-gated inwardly rectifying potassium channel KCNH2
inhibitor
Humans
UAlpha-1A adrenergic receptor
antagonist
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
UAlpha-1D adrenergic receptor
antagonist
Humans
Absorption

The absolute bioavailability of quinidine sulfate is approximately 70%, but it ranges from 45% to 100%. The less-than-complete quinidine sulfate bioavailability is a result of first-pass metabolism in the liver.5 In contrast, the absolute bioavailability of quinidine gluconate ranges from 70% to 80%, and relative to quinidine sulfate, quinidine from quinidine gluconate has a bioavailability of 1.03.6 The tmax of quinidine sulfate extended-release tablets is approximately 6 h5, while the tmax of quinidine gluconate goes from 3 to 5 h.6 The peak serum concentration reached with immediate-release quinidine sulfate is delayed for about an hour when taken with food. Furthermore, the ingestion of grapefruit juice may decrease the rate of absorption of quinidine.5,6

Volume of distribution

Quinidine has a volume of distribution of 2-3 L/kg in healthy young adults, 0.5 L/kg in patients with congestive heart failure, and 3-5 L/kg in patients with liver cirrhosis.5,6

Protein binding

From 6.5 to 16.2 µmol/L, 80 to 88% of quinidine is bound to plasma proteins, mainly α1-acid glycoprotein and albumin. This fraction is lower in pregnant women, and it may be as low as 50 to 70% in infants and neonates.5,6

Metabolism

Quinidine is mainly metabolized in the liver by cytochrome P450 enzymes, specifically CYP3A4. The major metabolite of quinidine is 3-hydroxy-quinidine, which has a volume of distribution larger than quinidine and an elimination half-life of about 12 hours.5,6 Non-clinical and clinical studies suggest that 3-hydroxy-quinidine has approximately half the antiarrhythmic activity of quinidine; therefore, this metabolite is partly responsible for the effects detected with the chronic use of quinidine.5,6

Hover over products below to view reaction partners

Route of elimination

The elimination of quinidine is achieved by the renal excretion of the unchanged drug (15 to 40% of total clearance) and its hepatic biotransformation to a variety of metabolites (60 to 85% of total clearance).4 When urine has a pH lower than 7, 20% of administered quinidine appears in urine unchanged. However, this proportion decreases to as little as 5% as it becomes more alkaline. The renal clearance of quinidine involves both glomerular filtration and active tubular secretion, moderated by pH-dependent tubular reabsorption.5,6

Half-life

The elimination half-life of quinidine is 6-8 hours in adults and 3-4 hours in pediatric patients.5,6

Clearance

The clearance of quinidine ranges from 3 to 5 mL/min/kg in adults. In pediatric patients, quinidine clearance may be two or three times as rapid.5,6

Adverse Effects
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Toxicity

Quinidine overdoses have been well described. The ingestion of 5 g of quinidine resulted in the death of a toddler, while an adolescent was reported to survive after ingesting 8 g of quinidine.5,6 A 16-month that ingested quinidine tablets developed a concretion of bezoar in the stomach, which led to non-declining toxic levels of quinidine. A gastric aspirate revealed that quinidine levels were 50 times higher than the ones detected in plasma. In cases of massive overdose, it may be appropriate to perform an endoscopy.5 Acute quinidine overdoses are characterized by ventricular arrhythmias and hypotension. Other signs and symptoms of quinidine overdose may include vomiting, diarrhea, tinnitus, high-frequency hearing loss, vertigo, blurred vision, diplopia, photophobia, headache, confusion and delirium.5,6

Pathways
PathwayCategory
Quinidine Action PathwayDrug action
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
AbacavirAbacavir may decrease the excretion rate of Quinidine which could result in a higher serum level.
AbametapirThe serum concentration of Quinidine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Quinidine can be increased when combined with Abatacept.
AbciximabThe therapeutic efficacy of Abciximab can be increased when used in combination with Quinidine.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Quinidine.
Food Interactions
  • Exercise caution with grapefruit products. Grapefruit may delay the absorption of quinidine, and inhibit its metabolism through CYP3A4.
  • Exercise caution with St. John's Wort.
  • Take separate from antacids. Antacids may reduce the absorption of quinidine.
  • Take with or without food. Taking quinidine with food may slow its absorption.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Quinidine gluconateR6875N380F7054-25-3XHKUDCCTVQUHJQ-LCYSNFERSA-N
Quinidine hydrochlorideS4P5V5597B1668-99-1LBSFSRMTJJPTCW-VJAUXQICSA-N
Quinidine polygalacturonateH0C54E9D6827555-34-6Not applicable
Quinidine sulfateJ13S2394HE6591-63-5LOUPRKONTZGTKE-UYVJDWJCSA-N
Product Images
International/Other Brands
Cardioquin / Kinidin / Quin-Release / Quinaglute / Quinalan / Quinicardine / Quinidex
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Cardioquin TabletsTablet275 mg / tabOralPurdue Pharma1961-12-312000-07-17Canada flag
Quinate Tab 325mgTablet325 mgOralRougier Pharma Division Of Ratiopharm Inc1979-12-312003-09-22Canada flag
Quinidex Extentabs Srt 300mgTablet, extended release300 mg / srtOralWyeth Ayerst Canada Inc.1994-12-312001-10-29Canada flag
Quinidex Extentabs Srt 300mgTablet, extended release300 mgOralAyerst Laboratories1991-12-311996-09-10Canada flag
Quinidine 200 TabTablet200 mgOralPro Doc Limitee1982-12-312003-07-31Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo Quinidine Tab 200mgTablet200 mgOralApotex Corporation1979-12-312010-01-19Canada flag
Apo-quin-G Tab 325mgTablet325 mgOralApotex Corporation1985-12-312010-01-19Canada flag
Novo-quinidin 200mgTablet200 mgOralNovopharm Limited1966-12-312005-08-10Canada flag
Quinidine GluconateTablet, extended release324 mg/1OralPhysicians Total Care, Inc.1987-02-112012-06-30US flag
Quinidine gluconateTablet, extended release324 mg/1OralEywa Pharma Inc2022-03-20Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
NuedextaQuinidine sulfate (10 mg/1) + Dextromethorphan hydrobromide monohydrate (20 mg/1)Capsule, gelatin coatedOralAvanir Pharmaceuticals2010-12-01Not applicableUS flag
NuedextaQuinidine sulfate (10 mg/1) + Dextromethorphan hydrobromide monohydrate (20 mg/1)Capsule, gelatin coatedOralOtsuka Pharmaceutical Netherlands Bv2023-01-03Not applicableUS flag

Categories

ATC Codes
C01BA01 — QuinidineC01BA51 — Quinidine, combinations excl. psycholepticsC01BA71 — Quinidine, combinations with psycholeptics
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as cinchona alkaloids. These are alkaloids structurally characterized by the presence of the cinchonan skeleton, which consists of a quinoline linked to an azabicyclo[2.2.2]octane moiety.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Cinchona alkaloids
Sub Class
Not Available
Direct Parent
Cinchona alkaloids
Alternative Parents
4-quinolinemethanols / Quinuclidines / Anisoles / Aralkylamines / Alkyl aryl ethers / Pyridines and derivatives / Piperidines / Heteroaromatic compounds / Trialkylamines / Secondary alcohols
show 5 more
Substituents
1,2-aminoalcohol / 4-quinolinemethanol / Alcohol / Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic alcohol / Aromatic heteropolycyclic compound / Azacycle
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cinchona alkaloid (CHEBI:28593)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
ITX08688JL
CAS number
56-54-2
InChI Key
LOUPRKONTZGTKE-LHHVKLHASA-N
InChI
InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19+,20-/m0/s1
IUPAC Name
(S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol
SMILES
[H][C@@]12CCN(C[C@@H]1C=C)[C@]([H])(C2)[C@@H](O)C1=C2C=C(OC)C=CC2=NC=C1

References

Synthesis Reference

Jean Paul REMON, Chris Vervaet, "QUININE AND QUINIDINE SALTS, METHODS FOR MAKING THEM, AND PHARMACEUTICAL FORMULATIONS COMPRISING THEM." U.S. Patent US20090239900, issued September 24, 2009.

US20090239900
General References
  1. Yang F, Hanon S, Lam P, Schweitzer P: Quinidine revisited. Am J Med. 2009 Apr;122(4):317-21. doi: 10.1016/j.amjmed.2008.11.019. Epub 2009 Feb 25. [Article]
  2. Vitali Serdoz L, Rittger H, Furlanello F, Bastian D: Quinidine-A legacy within the modern era of antiarrhythmic therapy. Pharmacol Res. 2019 Jun;144:257-263. doi: 10.1016/j.phrs.2019.04.028. Epub 2019 Apr 23. [Article]
  3. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013 Dec;10(12):1932-63. doi: 10.1016/j.hrthm.2013.05.014. Epub 2013 Aug 30. [Article]
  4. Ochs HR, Greenblatt DJ, Woo E: Clinical pharmacokinetics of quinidine. Clin Pharmacokinet. 1980 Mar-Apr;5(2):150-68. doi: 10.2165/00003088-198005020-00003. [Article]
  5. FDA Approved Drug Products: Quinidex Extentabs (quinidine sulfate) extended-release tablets for oral use [Link]
  6. FDA Approved Drug Products: Quinidine gluconate extended-release tablets for oral use [Link]
Human Metabolome Database
HMDB0015044
KEGG Drug
D08458
KEGG Compound
C06527
PubChem Compound
441074
PubChem Substance
46505356
ChemSpider
389880
BindingDB
50121975
RxNav
9068
ChEBI
28593
ChEMBL
CHEMBL1294
ZINC
ZINC000003831405
Therapeutic Targets Database
DAP000515
PharmGKB
PA451209
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
QDN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Quinidine
PDB Entries
4wnu / 6lqa
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4CompletedNot AvailableParoxysmal Atrial Fibrillation (PAF)1somestatusstop reasonjust information to hide
4CompletedTreatmentDementia / Pseudobulbar Affect (PBA) / Stroke / Traumatic Brain Injury (TBI)1somestatusstop reasonjust information to hide
4TerminatedOtherPseudobulbar Affect (Involuntary Laughing and/or Crying)1somestatusstop reasonjust information to hide
4TerminatedSupportive CareAlzheimer's Disease (AD) / Pseudobulbar Affect (PBA)1somestatusstop reasonjust information to hide
3CompletedPreventionArrhythmia / Cardiac Arrest / Cardiovascular Disease (CVD) / Myocardial Infarction / Ventricular Fibrillation1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
  • Warner chilcott div warner lambert co
  • Bayer healthcare pharmaceuticals inc
  • Lannett co inc
  • Watson laboratories inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Halsey drug co inc
  • Mutual pharmaceutical co inc
  • Roxane laboratories inc
  • Sandoz inc
  • Superpharm corp
  • Pharmaceutical research assoc inc
  • Solvay pharmaceuticals
  • Wyeth pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Barr laboratories inc
  • Clonmel healthcare ltd
  • Contract pharmacal corp
  • Elkins sinn div ah robins co inc
  • Everylife
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • King pharmaceuticals inc
  • Kv pharmaceutical co
  • Lederle laboratories div american cyanamid co
  • L perrigo co
  • Pharmavite pharmaceuticals
  • Purepac pharmaceutical co
  • Scherer laboratories inc
  • Usl pharma inc
  • Valeant pharmaceuticals international
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Key pharmaceuticals inc sub schering plough corp
  • Schering corp
Packagers
  • Amend
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • Consolidated Midland Corp.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Eli Lilly & Co.
  • Eon Labs
  • H and H Laboratories
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Qualitest
  • Resource Optimization and Innovation LLC
  • Richmond Pharmacy
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral275 mg / tab
TabletOral
Capsule
Capsule, gelatin coatedOral
TabletOral325 mg
Tablet, extended releaseOral300 mg / srt
Tablet, extended releaseOral300 mg
SolutionIntravenous80 mg/1mL
Tablet, extended releaseOral324 mg/1
LiquidIntramuscular; Intravenous80 mg / mL
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral300 mg/1
Tablet, film coated, extended releaseOral300 mg/1
SolutionIntramuscular190 mg / mL
TabletOral195 mg
TabletOral200 mg
Prices
Unit descriptionCostUnit
Quinidine gluc 80 mg/ml vial2.16USD ml
Quinidine sulfate crystals1.58USD g
QuiNIDine Gluconate CR 324 mg Controlled Release Tabs0.97USD tab
Quinidine gluc er 324 mg tab0.93USD each
Quinidine Sulfate 300 mg0.41USD tablet
Quinidine sulfate 300 mg tablet0.4USD tablet
Quinidine Sulfate 200 mg0.22USD tablet
Quinidine sulfate 200 mg tablet0.21USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7659282No2010-02-092026-08-13US flag
US8227484No2012-07-242023-07-17US flag
USRE38115No2003-05-062016-01-26US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)174 °CPhysProp
water solubility140 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.44HANSCH,C ET AL. (1995)
logS-3.37ADME Research, USCD
Caco2 permeability-4.69ADME Research, USCD
pKa8.56 (at 25 °C)SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.334 mg/mLALOGPS
logP2.82ALOGPS
logP2.51Chemaxon
logS-3ALOGPS
pKa (Strongest Acidic)13.89Chemaxon
pKa (Strongest Basic)9.05Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area45.59 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity94.69 m3·mol-1Chemaxon
Polarizability35.64 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9836
Blood Brain Barrier+0.9382
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor IInhibitor0.8208
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterInhibitor0.762
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5754
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7225
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.972
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0596 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5884
hERG inhibition (predictor II)Inhibitor0.538
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (2.96 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4r-1901000000-90466d795da1be8cafae
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-02ta-3900000000-46a157d2899290cbf4ab
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0200-2952000000-2777ab3374ec2b052b2e
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0bt9-0908000000-f7ff24907014d8850472
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-08fr-0907000000-f6d31042d549da6bcfd0
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0bt9-0709000000-2c0e665e2c3031c8e517
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-00di-0009133000-a893d9e0e441c597fac3
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-00di-0009001000-0a0220fd8eeb9e62bc20
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0469000000-3679f13f09481b3563c8
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0459000000-60c4a39356a4afeef2d2
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0239000000-644b48bb63dd87dac231
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0910000000-b0045fccdbe90e598912
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0229000000-f88b510f13aab6a2bb44
MS/MS Spectrum - , positiveLC-MS/MSsplash10-02ta-3900000000-46a157d2899290cbf4ab
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0200-2952000000-2777ab3374ec2b052b2e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-bc68328282c6154e03d3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00dl-0169000000-482414433c1e7b0ca89d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-4808a6e84b0cb2d4cbc6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fr-0519000000-2b2e0c890198ec71ca0c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0920000000-01da964eb26702c0e20a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ab9-0910000000-a1ffa729b41cabf4fc88
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]-190.4705787
predicted
DarkChem Lite v0.1.0
[M-H]-190.0769787
predicted
DarkChem Lite v0.1.0
[M-H]-192.3502787
predicted
DarkChem Lite v0.1.0
[M-H]-179.83675
predicted
DeepCCS 1.0 (2019)
[M+H]+190.9457787
predicted
DarkChem Lite v0.1.0
[M+H]+190.3559787
predicted
DarkChem Lite v0.1.0
[M+H]+192.8521787
predicted
DarkChem Lite v0.1.0
[M+H]+182.23232
predicted
DeepCCS 1.0 (2019)
[M+Na]+190.6905787
predicted
DarkChem Lite v0.1.0
[M+Na]+190.1989787
predicted
DarkChem Lite v0.1.0
[M+Na]+192.5574787
predicted
DarkChem Lite v0.1.0
[M+Na]+188.14485
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity)
Specific Function
ankyrin binding
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Stokoe KS, Thomas G, Goddard CA, Colledge WH, Grace AA, Huang CL: Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/Delta murine hearts modelling long QT syndrome 3. J Physiol. 2007 Jan 1;578(Pt 1):69-84. Epub 2006 Oct 5. [Article]
  2. Itoh H, Shimizu M, Takata S, Mabuchi H, Imoto K: A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs. J Cardiovasc Electrophysiol. 2005 May;16(5):486-93. [Article]
  3. Grant AO: Electrophysiological basis and genetics of Brugada syndrome. J Cardiovasc Electrophysiol. 2005 Sep;16 Suppl 1:S3-7. [Article]
  4. Napolitano C, Priori SG: Brugada syndrome. Orphanet J Rare Dis. 2006 Sep 14;1:35. [Article]
  5. Ohgo T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Ohe T, Shimizu W: Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation. Heart Rhythm. 2007 Jun;4(6):695-700. Epub 2007 Feb 20. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Sheets MF, Fozzard HA, Lipkind GM, Hanck DA: Sodium channel molecular conformations and antiarrhythmic drug affinity. Trends Cardiovasc Med. 2010 Jan;20(1):16-21. doi: 10.1016/j.tcm.2010.03.002. [Article]
  8. Tella SR, Goldberg SR: Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:15820677, PubMed:21653227). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium (PubMed:21653227, PubMed:22431633). The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:15820677, PubMed:21653227, PubMed:22431633, PubMed:23169818, PubMed:25001086, PubMed:8605869, PubMed:8978667). Channel activity is modulated by activation of serotonin receptors (By similarity). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (By similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity (PubMed:23169818). Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (PubMed:23169818). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (By similarity). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (By similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity). Required for normal ion and water transport in the kidney (By similarity). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (By similarity). The low channel activity of homodimeric KCNK1 may be due to sumoylation (PubMed:15820677, PubMed:20498050, PubMed:23169818). The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed:19959478). Permeable to monovalent cations with ion selectivity for K(+) > Rb(+) >> NH4(+) >> Cs(+) = Na(+) = Li(+)
Specific Function
identical protein binding
Gene Name
KCNK1
Uniprot ID
O00180
Uniprot Name
Potassium channel subfamily K member 1
Molecular Weight
38142.775 Da
References
  1. Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J: TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. EMBO J. 1996 Mar 1;15(5):1004-11. [Article]
  2. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M: Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996 Dec 16;15(24):6854-62. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Exhibits outward rectification in a physiological K(+) gradient and mild inward rectification in symmetrical K(+) conditions
Specific Function
inward rectifier potassium channel activity
Gene Name
KCNK6
Uniprot ID
Q9Y257
Uniprot Name
Potassium channel subfamily K member 6
Molecular Weight
33746.8 Da
References
  1. Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honore E: TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem. 2000 Sep 15;275(37):28722-30. [Article]
  2. Guerard NC, Traebert M, Suter W, Dumotier BM: Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart. J Pharmacol Toxicol Methods. 2008 Jul-Aug;58(1):32-40. doi: 10.1016/j.vascn.2008.05.129. Epub 2008 Jun 8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
Specific Function
delayed rectifier potassium channel activity
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Voltage-gated inwardly rectifying potassium channel KCNH2
Molecular Weight
126653.52 Da
References
  1. Po SS, Wang DW, Yang IC, Johnson JP Jr, Nie L, Bennett PB: Modulation of HERG potassium channels by extracellular magnesium and quinidine. J Cardiovasc Pharmacol. 1999 Feb;33(2):181-5. [Article]
  2. Dong DL, Li Z, Wang HZ, Du ZM, Song WH, Yang BF: Acidification alters antiarrhythmic drug blockade of the ether-a-go-go-related Gene (HERG) Channels. Basic Clin Pharmacol Toxicol. 2004 May;94(5):209-12. [Article]
  3. Wolpert C, Schimpf R, Giustetto C, Antzelevitch C, Cordeiro J, Dumaine R, Brugada R, Hong K, Bauersfeld U, Gaita F, Borggrefe M: Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. [Article]
  4. Lin C, Ke X, Cvetanovic I, Ranade V, Somberg J: The influence of extracellular acidosis on the effect of IKr blockers. J Cardiovasc Pharmacol Ther. 2005 Mar;10(1):67-76. [Article]
  5. Lin C, Cvetanovic I, Ke X, Ranade V, Somberg J: A mechanism for the potential proarrhythmic effect of acidosis, bradycardia, and hypokalemia on the blockade of human ether-a-go-go-related gene (HERG) channels. Am J Ther. 2005 Jul-Aug;12(4):328-36. [Article]
  6. Guerard NC, Traebert M, Suter W, Dumotier BM: Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart. J Pharmacol Toxicol Methods. 2008 Jul-Aug;58(1):32-40. doi: 10.1016/j.vascn.2008.05.129. Epub 2008 Jun 8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes
Specific Function
alpha1-adrenergic receptor activity
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes
Specific Function
alpha1-adrenergic receptor activity
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
Specific Function
alpha1-adrenergic receptor activity
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Shibata K, Hirasawa A, Foglar R, Ogawa S, Tsujimoto G: Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5'-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. [Article]
  2. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [Article]
  3. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [Article]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
Specific Function
all-trans retinoic acid 18-hydroxylase activity
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57469.95 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Details
3. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Berka K, Anzenbacherova E, Hendrychova T, Lange R, Masek V, Anzenbacher P, Otyepka M: Binding of quinidine radically increases the stability and decreases the flexibility of the cytochrome P450 2D6 active site. J Inorg Biochem. 2012 May;110:46-50. doi: 10.1016/j.jinorgbio.2012.02.010. Epub 2012 Feb 22. [Article]
  2. Hutzler JM, Walker GS, Wienkers LC: Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9. doi: 10.1021/tx025674x. [Article]
  3. von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9. doi: 10.1021/js980197h. [Article]
  4. Bramer SL, Suri A: Inhibition of CYP2D6 by quinidine and its effects on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37 Suppl 2:41-51. [Article]
  5. Branch RA, Adedoyin A, Frye RF, Wilson JW, Romkes M: In vivo modulation of CYP enzymes by quinidine and rifampin. Clin Pharmacol Ther. 2000 Oct;68(4):401-11. doi: 10.1067/mcp.2000.110561. [Article]
  6. McLaughlin LA, Paine MJ, Kemp CA, Marechal JD, Flanagan JU, Ward CJ, Sutcliffe MJ, Roberts GC, Wolf CR: Why is quinidine an inhibitor of cytochrome P450 2D6? The role of key active-site residues in quinidine binding. J Biol Chem. 2005 Nov 18;280(46):38617-24. doi: 10.1074/jbc.M505974200. Epub 2005 Sep 14. [Article]
  7. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 Da
References
  1. Ching MS, Blake CL, Malek NA, Angus PW, Ghabrial H: Differential inhibition of human CYP1A1 and CYP1A2 by quinidine and quinine. Xenobiotica. 2001 Nov;31(11):757-67. doi: 10.1080/00498250110065603 . [Article]
  2. Munch M, Heegaard C, Jensen PH, Andreasen PA: Type-1 inhibitor of plasminogen activators. Distinction between latent, activated and reactive centre-cleaved forms with thermal stability and monoclonal antibodies. FEBS Lett. 1991 Dec 16;295(1-3):102-6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
Specific Function
4-nitrophenol 2-monooxygenase activity
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Nielsen TL, Rasmussen BB, Flinois JP, Beaune P, Brosen K: In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. J Pharmacol Exp Ther. 1999 Apr;289(1):31-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
Specific Function
arachidonic acid monooxygenase activity
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. van Montfoort JE, Hagenbuch B, Fattinger KE, Muller M, Groothuis GM, Meijer DK, Meier PJ: Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations. J Pharmacol Exp Ther. 1999 Oct;291(1):147-52. [Article]
  2. Ching MS, Blake CL, Malek NA, Angus PW, Ghabrial H: Differential inhibition of human CYP1A1 and CYP1A2 by quinidine and quinine. Xenobiotica. 2001 Nov;31(11):757-67. doi: 10.1080/00498250110065603 . [Article]
  3. Lu AY, Wang RW, Lin JH: Cytochrome P450 in vitro reaction phenotyping: a re-evaluation of approaches used for P450 isoform identification. Drug Metab Dispos. 2003 Apr;31(4):345-50. doi: 10.1124/dmd.31.4.345. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Spracklin DK, Thummel KE, Kharasch ED: Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4. Drug Metab Dispos. 1996 Sep;24(9):976-83. [Article]
  2. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M: Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica. 2000 Apr;30(4):327-43. [Article]
  2. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5'-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Functions as a 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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
Specific Function
Not Available
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23539.43 Da
References
  1. Li JH, Xu JQ, Cao XM, Ni L, Li Y, Zhuang YY, Gong JB: Influence of the ORM1 phenotypes on serum unbound concentration and protein binding of quinidine. Clin Chim Acta. 2002 Mar;317(1-2):85-92. [Article]
  2. McCollam PL, Crouch MA, Arnaud P: Caucasian versus African-American differences in orosomucoid: potential implications for therapy. Pharmacotherapy. 1998 May-Jun;18(3):620-6. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
acetylcholine transmembrane transporter activity
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [Article]
  2. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. [Article]
  3. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ: Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5. [Article]
  2. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [Article]
  3. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [Article]
  4. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [Article]
  5. Zhang L, Gorset W, Dresser MJ, Giacomini KM: The interaction of n-tetraalkylammonium compounds with a human organic cation transporter, hOCT1. J Pharmacol Exp Ther. 1999 Mar;288(3):1192-8. [Article]
  6. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. [Article]
  7. Sinclair CJ, Chi KD, Subramanian V, Ward KL, Green RM: Functional expression of a high affinity mammalian hepatic choline/organic cation transporter. J Lipid Res. 2000 Nov;41(11):1841-8. [Article]
  8. Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H: Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol. 2001 Sep;281(3):F454-68. [Article]
  9. Urakami Y, Okuda M, Masuda S, Saito H, Inui KI: Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J Pharmacol Exp Ther. 1998 Nov;287(2):800-5. [Article]
  10. Martel F, Vetter T, Russ H, Grundemann D, Azevedo I, Koepsell H, Schomig E: Transport of small organic cations in the rat liver. The role of the organic cation transporter OCT1. Naunyn Schmiedebergs Arch Pharmacol. 1996 Aug-Sep;354(3):320-6. [Article]
  11. Busch AE, Quester S, Ulzheimer JC, Gorboulev V, Akhoundova A, Waldegger S, Lang F, Koepsell H: Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1. FEBS Lett. 1996 Oct 21;395(2-3):153-6. [Article]
  12. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. [Article]
  13. Tu M, Sun S, Wang K, Peng X, Wang R, Li L, Zeng S, Zhou H, Jiang H: Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity. Toxicology. 2013 Sep 15;311(3):225-30. doi: 10.1016/j.tox.2013.06.009. Epub 2013 Jul 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Organic cation/carnitine transporter 2
Molecular Weight
62751.08 Da
References
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [Article]
  2. Ohashi R, Tamai I, Nezu Ji J, Nikaido H, Hashimoto N, Oku A, Sai Y, Shimane M, Tsuji A: Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol Pharmacol. 2001 Feb;59(2):358-66. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [Article]
  2. Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [Article]
  3. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [Article]
  4. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [Article]
  5. Horie K, Tang F, Borchardt RT: Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res. 2003 Feb;20(2):161-8. [Article]
  6. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
  7. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. [Article]
  8. Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, Hori R: Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther. 1992 Nov;263(2):840-5. [Article]
  9. Ito T, Yano I, Tanaka K, Inui KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther. 1997 Aug;282(2):955-60. [Article]
  10. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, Wilkinson GR: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest. 1998 Jan 15;101(2):289-94. [Article]
  11. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
  12. Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [Article]
  13. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. doi: 10.1152/ajpgi.00102.2009. Epub 2009 Jun 18. [Article]
  14. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. doi: 10.1208/s12248-009-9092-5. Epub 2009 Mar 25. [Article]
  15. Smith BJ, Doran AC, McLean S, Tingley FD 3rd, O'Neill BT, Kajiji SM: P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists. J Pharmacol Exp Ther. 2001 Sep;298(3):1252-9. [Article]
  16. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [Article]
  17. Neuhoff S, Ungell AL, Zamora I, Artursson P: pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Pharm Res. 2003 Aug;20(8):1141-8. [Article]
  18. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [Article]
  19. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. [Article]
  20. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM: Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine [seecomments]. Circulation. 1999 Feb 2;99(4):552-7. [Article]
  21. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ: Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5. [Article]
  2. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [Article]
  3. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. [Article]
  4. van Montfoort JE, Hagenbuch B, Fattinger KE, Muller M, Groothuis GM, Meijer DK, Meier PJ: Polyspecific organic anion transporting polypeptides mediate hepatic uptake of amphipathic type II organic cations. J Pharmacol Exp Ther. 1999 Oct;291(1):147-52. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
References
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
Specific Function
ABC-type glutathione S-conjugate transporter activity
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
ATP-binding cassette sub-family C member 2
Molecular Weight
174205.64 Da
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:10215651, PubMed:15107849, PubMed:15795384, PubMed:16729965, PubMed:20601551, PubMed:22206629, PubMed:22569296, PubMed:29530864). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (PubMed:15795384, PubMed:29530864, PubMed:33124720). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (PubMed:22206629). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (PubMed:22206629, PubMed:22569296). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:15795384, PubMed:22206629). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (PubMed:35307651)
Specific Function
acetylcholine transmembrane transporter activity
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Nozawa T, Tamai I, Sai Y, Nezu J, Tsuji A: Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin. J Pharm Pharmacol. 2003 Jul;55(7):1013-20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
Specific Function
ABC-type bile acid transporter activity
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wilson A. (2016). New horizons in predictive drug metabolism and pharmacokinetics. The Royal Society of Chemistry. [ISBN:978-1-84973-828-6]

Drug created at June 13, 2005 13:24 / Updated at October 13, 2024 00:21