Identification

Name
Perhexiline
Accession Number
DB01074  (APRD00107)
Type
Small Molecule
Groups
Approved, Investigational
Description

2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [PubChem]

Structure
Thumb
Synonyms
  • (-)-2-(2,2-Dicyclohexylethyl)piperidine
  • (+)-2-(2,2-Dicyclohexylethyl)piperidine
  • 2-(2,2-Dicyclohexylethyl)piperidine
  • Perhexilene
  • Perhexilina
  • Perhexiline
  • Perhexilinum
  • Perhexilline
Categories
UNII
KU65374X44
CAS number
6621-47-2
Weight
Average: 277.4879
Monoisotopic: 277.276950125
Chemical Formula
C19H35N
InChI Key
CYXKNKQEMFBLER-UHFFFAOYSA-N
InChI
InChI=1S/C19H35N/c1-3-9-16(10-4-1)19(17-11-5-2-6-12-17)15-18-13-7-8-14-20-18/h16-20H,1-15H2
IUPAC Name
2-(2,2-dicyclohexylethyl)piperidine
SMILES
C(C(C1CCCCC1)C1CCCCC1)C1CCCCN1

Pharmacology

Indication

For the management of severe angina pectoris.

Pharmacodynamics

Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures.

Mechanism of action

Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1 and CPT-2. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT-1 and, to a lesser extent, CPT-2, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O2 consumption as before and consequently increases myocardial efficiency.

TargetActionsOrganism
ACarnitine O-palmitoyltransferase 1, liver isoform
inhibitor
Human
ACarnitine O-palmitoyltransferase 2, mitochondrial
inhibitor
Human
UPotassium voltage-gated channel subfamily H member 2Not AvailableHuman
Absorption

Well absorbed (>80%) from the gastrointestinal tract following oral administration.

Volume of distribution
Not Available
Protein binding

Perhexiline and its metabolites are highly protein bound (>90%).

Metabolism

The principal metabolites of perhexiline in man are monohydroxyperhexiline (which is excreted, in part, conjugated with glucuronic acid) and dihydroxyperhexiline that accounts for a relatively small proportion of the total metabolites. Two unidentified metabolites have also been found in the faeces. The pharmacological activity of the metabolites is not known. Hydroxylation of perhexiline is controlled by cytochrome P450 2D6 (CY P450 2D6).

Route of elimination
Not Available
Half life

Variable and non-linear. Some reports show a half-life of 2-6 days, others indicate it could be as high as 30 days.

Clearance
Not Available
Toxicity

Oral LD50 rat: 2150 mg/kg; Oral LD50 Mouse: 2641 mg/kg. Short term adverse effects include nausea, transient dizziness, hypoglycaemia in diabetic patients, and torsade de pointes (rare).

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

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Perhexiline can be increased when it is combined with Abiraterone.Approved
Acetyl sulfisoxazoleThe metabolism of Perhexiline can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AmiodaroneThe metabolism of Perhexiline can be decreased when combined with Amiodarone.Approved, Investigational
ApalutamideThe serum concentration of Perhexiline can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Perhexiline can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Perhexiline can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Perhexiline can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Perhexiline can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Perhexiline can be decreased when combined with Betaxolol.Approved, Investigational
BoceprevirThe metabolism of Perhexiline can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Perhexiline can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Perhexiline can be decreased when it is combined with Bosentan.Approved, Investigational
BupropionThe metabolism of Perhexiline can be decreased when combined with Bupropion.Approved
CarbamazepineThe metabolism of Perhexiline can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Perhexiline can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Perhexiline can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Perhexiline can be decreased when combined with Chloroquine.Approved, Investigational, Vet Approved
ChlorpromazineThe metabolism of Perhexiline can be decreased when combined with Chlorpromazine.Approved, Investigational, Vet Approved
CholecalciferolThe metabolism of Perhexiline can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Perhexiline can be decreased when combined with Cimetidine.Approved, Investigational
CinacalcetThe metabolism of Perhexiline can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Perhexiline can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Perhexiline can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Perhexiline can be decreased when combined with Clemastine.Approved, Investigational
ClobazamThe metabolism of Perhexiline can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Perhexiline can be decreased when combined with Clomipramine.Approved, Investigational, Vet Approved
ClopidogrelThe metabolism of Perhexiline can be decreased when combined with Clopidogrel.Approved
ClotrimazoleThe metabolism of Perhexiline can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Perhexiline can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Perhexiline can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Perhexiline can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Perhexiline.Approved, Investigational
CrizotinibThe metabolism of Perhexiline can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Perhexiline can be decreased when combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Perhexiline can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Perhexiline can be decreased when it is combined with Dabrafenib.Approved, Investigational
DarifenacinThe metabolism of Perhexiline can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Perhexiline can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Perhexiline can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Perhexiline can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Perhexiline can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Perhexiline can be decreased when combined with Desipramine.Approved, Investigational
DihydroergotamineThe metabolism of Perhexiline can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of Perhexiline can be decreased when combined with Diltiazem.Approved, Investigational
DiphenhydramineThe metabolism of Perhexiline can be decreased when combined with Diphenhydramine.Approved, Investigational
DosulepinThe metabolism of Perhexiline can be decreased when combined with Dosulepin.Approved
DoxorubicinThe metabolism of Perhexiline can be decreased when combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Perhexiline can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Perhexiline can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Perhexiline can be decreased when combined with Duloxetine.Approved
EliglustatThe metabolism of Perhexiline can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Perhexiline can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Perhexiline can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Perhexiline.Approved
FluconazoleThe metabolism of Perhexiline can be decreased when combined with Fluconazole.Approved, Investigational
FluoxetineThe metabolism of Perhexiline can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Perhexiline can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Perhexiline can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Perhexiline can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Perhexiline can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Perhexiline can be increased when it is combined with Fusidic Acid.Approved, Investigational
HaloperidolThe metabolism of Perhexiline can be decreased when combined with Haloperidol.Approved
IdelalisibThe metabolism of Perhexiline can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Perhexiline can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Perhexiline can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Perhexiline can be decreased when combined with Indinavir.Approved
IsavuconazoleThe serum concentration of Perhexiline can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Perhexiline can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Perhexiline can be decreased when combined with Isoniazid.Approved, Investigational
IsradipineThe metabolism of Perhexiline can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of Perhexiline can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Perhexiline can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Perhexiline can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Perhexiline can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Perhexiline can be decreased when combined with Lorcaserin.Approved
LorpiprazoleThe serum concentration of Perhexiline can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe metabolism of Perhexiline can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Perhexiline can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Perhexiline can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Perhexiline can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Perhexiline can be decreased when combined with Manidipine.Approved, Investigational
MethadoneThe metabolism of Perhexiline can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Perhexiline can be decreased when combined with Methotrimeprazine.Approved, Investigational
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Perhexiline.Approved, Investigational
MidostaurinThe metabolism of Perhexiline can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Perhexiline can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Perhexiline can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Perhexiline can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Perhexiline can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Perhexiline can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Perhexiline can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Perhexiline can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Perhexiline can be decreased when combined with Nicardipine.Approved, Investigational
NilotinibThe metabolism of Perhexiline can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Perhexiline can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Perhexiline can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Perhexiline can be increased when it is combined with Palbociclib.Approved, Investigational
PanobinostatThe serum concentration of Perhexiline can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Perhexiline can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Perhexiline can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Perhexiline can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Perhexiline can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Perhexiline can be increased when combined with Phenytoin.Approved, Vet Approved
PitolisantThe serum concentration of Pitolisant can be increased when it is combined with Perhexiline.Approved, Investigational
PosaconazoleThe metabolism of Perhexiline can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Perhexiline can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Perhexiline can be decreased when combined with Promazine.Approved, Vet Approved
QuazepamThe serum concentration of Perhexiline can be increased when it is combined with Quazepam.Approved, Illicit
QuinidineThe metabolism of Perhexiline can be decreased when combined with Quinidine.Approved, Investigational
QuinineThe metabolism of Perhexiline can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Perhexiline can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Perhexiline can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Perhexiline can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Perhexiline can be increased when combined with Rifapentine.Approved, Investigational
RitonavirThe metabolism of Perhexiline can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Perhexiline can be decreased when combined with Rolapitant.Approved, Investigational
RopiniroleThe metabolism of Perhexiline can be decreased when combined with Ropinirole.Approved, Investigational
RucaparibThe metabolism of Perhexiline can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe metabolism of Perhexiline can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Perhexiline can be decreased when used in combination with Sarilumab.Approved, Investigational
SertralineThe metabolism of Perhexiline can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Perhexiline can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Perhexiline can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Perhexiline can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Perhexiline can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Perhexiline can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Perhexiline can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Perhexiline can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Perhexiline can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Perhexiline can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Perhexiline can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Perhexiline.Approved, Withdrawn
ThiotepaThe metabolism of Perhexiline can be decreased when combined with Thiotepa.Approved, Investigational
TiclopidineThe metabolism of Perhexiline can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Perhexiline can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Perhexiline can be decreased when it is combined with Tocilizumab.Approved
TranylcypromineThe metabolism of Perhexiline can be decreased when combined with Tranylcypromine.Approved, Investigational
VemurafenibThe serum concentration of Perhexiline can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Perhexiline can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Perhexiline can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Perhexiline can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Perhexiline can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

Synthesis Reference

Stephen W. Horgan, Frank P. Palopoli, Edward J. Schwoegler, "Process for preparing 2-(2,2-dicyclohexylethyl)piperidine." U.S. Patent US4069222, issued August, 1950.

US4069222
General References
Not Available
External Links
Human Metabolome Database
HMDB0015207
PubChem Compound
4746
PubChem Substance
46504471
ChemSpider
4584
BindingDB
61402
ChEBI
35553
ChEMBL
CHEMBL75880
Therapeutic Targets Database
DAP000957
PharmGKB
PA130150436
Wikipedia
Perhexiline
ATC Codes
C08EX02 — Perhexiline
MSDS
Download (25.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Unknown StatusBasic ScienceDiabetic Cardiomyopathy1
2CompletedTreatmentChronic Heart Failure (CHF)1
2CompletedTreatmentDiastolic Heart Failure1
2CompletedTreatmentHypertrophic Cardiomyopathy1
2RecruitingTreatmentCardiomyopathy, Hypertrophic, Familial / Hypertrophic Cardiomyopathy1
2, 3CompletedTreatmentCardiac Output, Low / Myocardial Reperfusion Injury1
2, 3Unknown StatusTreatmentCardiac Output, Low / Left Ventricular Hypertrophy / Myocardial Reperfusion Injury1
3WithdrawnTreatmentHypertrophic Cardiomyopathy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.0608 mg/LNot Available
logP6.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.72e-05 mg/mLALOGPS
logP5.87ALOGPS
logP5.53ChemAxon
logS-7ALOGPS
pKa (Strongest Basic)10.58ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity87.23 m3·mol-1ChemAxon
Polarizability36.22 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9818
Blood Brain Barrier+0.9796
Caco-2 permeable+0.6799
P-glycoprotein substrateNon-substrate0.5484
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8888
Renal organic cation transporterInhibitor0.6665
CYP450 2C9 substrateNon-substrate0.8539
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8779
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8452
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9548
BiodegradationNot ready biodegradable0.8346
Rat acute toxicity2.7630 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7559
hERG inhibition (predictor II)Non-inhibitor0.6082
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-001i-9000000000-e8335ba9964dd32ada29
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as piperidines. These are compounds containing a piperidine ring, which is a saturated aliphatic six-member ring with one nitrogen atom and five carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Not Available
Direct Parent
Piperidines
Alternative Parents
Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Piperidine / Azacycle / Secondary amine / Secondary aliphatic amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine / Aliphatic heteromonocyclic compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
piperidines (CHEBI:35553)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Carnitine o-palmitoyltransferase activity
Specific Function
Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-o...
Gene Name
CPT1A
Uniprot ID
P50416
Uniprot Name
Carnitine O-palmitoyltransferase 1, liver isoform
Molecular Weight
88366.92 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Kennedy JA, Kiosoglous AJ, Murphy GA, Pelle MA, Horowitz JD: Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. J Cardiovasc Pharmacol. 2000 Dec;36(6):794-801. [PubMed:11117381]
  4. Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD: Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005 Dec;46(6):849-55. [PubMed:16306812]
  5. Kennedy JA, Unger SA, Horowitz JD: Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol. 1996 Jul 26;52(2):273-80. [PubMed:8694852]
  6. Ashrafian H, Horowitz JD, Frenneaux MP: Perhexiline. Cardiovasc Drug Rev. 2007 Spring;25(1):76-97. [PubMed:17445089]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Carnitine o-palmitoyltransferase activity
Specific Function
Not Available
Gene Name
CPT2
Uniprot ID
P23786
Uniprot Name
Carnitine O-palmitoyltransferase 2, mitochondrial
Molecular Weight
73776.335 Da
References
  1. Kennedy JA, Kiosoglous AJ, Murphy GA, Pelle MA, Horowitz JD: Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. J Cardiovasc Pharmacol. 2000 Dec;36(6):794-801. [PubMed:11117381]
  2. Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD: Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005 Dec;46(6):849-55. [PubMed:16306812]
  3. Kennedy JA, Unger SA, Horowitz JD: Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol. 1996 Jul 26;52(2):273-80. [PubMed:8694852]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Perrin MJ, Kuchel PW, Campbell TJ, Vandenberg JI: Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-a-go-go-related gene channels. Mol Pharmacol. 2008 Nov;74(5):1443-52. doi: 10.1124/mol.108.049056. Epub 2008 Aug 13. [PubMed:18701618]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on July 02, 2018 17:29