You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameEliglustat
Accession NumberDB09039
TypeSmall Molecule
GroupsApproved
Description

Eliglustat, marketed by Genzyme as CERDELGA, is a glucosylceramide synthase inhibitor indicated for the long-term treatment of type 1 Gaucher disease. Patients selected for treatment with Eliglustat undergo an FDA approved genotype test to establish if they are CYP2D6 EM (extensive metabolizers), IM (intermediate metabolizers), or PM (poor metabolizers), as the results of this test dictate the dosage of Eliglustat recommended. Eliglustat was approved for use by the FDA in August 2014.

Structure
Thumb
Synonyms
N-[(1R,2R)-1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-(1-pyrrolidinyl)-2-propanyl]octanamide
External Identifiers
  • A16AX10
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cerdelgacapsule84 mg/1oralGenzyme Corporation2014-09-03Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
eliglustat tartrate
ThumbNot applicableDBSALT001106
Categories
UNIIDR40J4WA67
CAS number491833-29-5
WeightAverage: 404.551
Monoisotopic: 404.267507647
Chemical FormulaC23H36N2O4
InChI KeyFJZZPCZKBUKGGU-AUSIDOKSSA-N
InChI
InChI=1S/C23H36N2O4/c1-2-3-4-5-6-9-22(26)24-19(17-25-12-7-8-13-25)23(27)18-10-11-20-21(16-18)29-15-14-28-20/h10-11,16,19,23,27H,2-9,12-15,17H2,1H3,(H,24,26)/t19-,23-/m1/s1
IUPAC Name
N-[(1R,2R)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl]octanimidic acid
SMILES
[H][C@](CN1CCCC1)(N=C(O)CCCCCCC)[C@]([H])(O)C1=CC2=C(OCCO2)C=C1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationEliglustat is indicated for the long-term treatment of type 1 Gaucher disease in patients who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) in treatment-naive and treatment-experienced adult patients.
PharmacodynamicsAccording to pharmacokinetic and pharmacodynamic modelling, plasma concentrations of 500ng/mL of eliglustat are predicted to increase mean concentration in the PR, QRS, and QTcF intervals of 22, 7, and 13 msec, respectively. (Taken from Cerdelga prescribing information).
Mechanism of actionEliglustat is a glucosylceramide synthase (IC50 = 10 ng/mL) specific inhibitor that acts as a substrate inhibitor of glucosylceramide.
Related Articles
AbsorptionIn CYP2D6 EMs (extensive metabolizers), median time to reach maximum plasma concentrations (tmax) occurs at 1.5 to 2 hours following multiple doses of eliglustat 84 mg twice daily.
Volume of distribution

835 L in CYP2D6 EMs (extensive metabolizers).

Protein binding76 to 83%.
Metabolism

Extensively metabolized, primarily by CYP2D6 and less so by CYP3A4. No active metabolites have been identified.

Route of eliminationUrine (41.8%) and feces (51.4%), mainly as metabolites after oral administration.
Half life6.5 hours in EM (extensive metabolizers) and 8.9 hours in PM (poor metabolizers).
Clearance

88 L/h (8.8%) in CYP2D6 EM (extensive metabolizers).

ToxicityIn rats, eliglustat increased pre-implantation loss at 30 and 100 mg/kg/day. In male mature rats, eliglustat showed reversible adverse affects on sperm morphology, germ cell necrosis, and sloughed cells in the epididymis.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral84 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6916802 No2002-04-292022-04-29Us
US7196205 No2002-04-292022-04-29Us
US7615573 No2002-04-292022-04-29Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.038 mg/mLALOGPS
logP3.79ALOGPS
logP1.46ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)5.21ChemAxon
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.52 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity114.28 m3·mol-1ChemAxon
Polarizability46 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Poole RM: Eliglustat: first global approval. Drugs. 2014 Oct;74(15):1829-36. doi: 10.1007/s40265-014-0296-3. [PubMed:25239269 ]
External Links
ATC CodesA16AX10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (376 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Eliglustat can be increased when it is combined with Abiraterone.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Eliglustat.
AprepitantThe serum concentration of Eliglustat can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Eliglustat can be increased when it is combined with Atazanavir.
BexaroteneThe serum concentration of Eliglustat can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Eliglustat can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Eliglustat can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Eliglustat.
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Eliglustat.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Eliglustat.
BupropionThe serum concentration of Eliglustat can be increased when it is combined with Bupropion.
CarbamazepineThe serum concentration of Eliglustat can be decreased when it is combined with Carbamazepine.
CelecoxibThe serum concentration of Eliglustat can be increased when it is combined with Celecoxib.
CimetidineThe serum concentration of Eliglustat can be increased when it is combined with Cimetidine.
CinacalcetThe serum concentration of Eliglustat can be increased when it is combined with Cinacalcet.
CitalopramCitalopram may increase the QTc-prolonging activities of Eliglustat.
ClobazamThe serum concentration of Eliglustat can be increased when it is combined with Clobazam.
ClomipramineThe serum concentration of Eliglustat can be increased when it is combined with Clomipramine.
CobicistatThe serum concentration of Eliglustat can be increased when it is combined with Cobicistat.
CocaineThe serum concentration of Eliglustat can be increased when it is combined with Cocaine.
CodeineThe therapeutic efficacy of Codeine can be decreased when used in combination with Eliglustat.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Eliglustat.
ConivaptanThe serum concentration of Eliglustat can be increased when it is combined with Conivaptan.
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Eliglustat.
DabrafenibThe serum concentration of Eliglustat can be decreased when it is combined with Dabrafenib.
DarifenacinThe serum concentration of Eliglustat can be increased when it is combined with Darifenacin.
DarunavirThe serum concentration of Eliglustat can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Eliglustat can be decreased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Eliglustat can be increased when it is combined with Delavirdine.
DesipramineThe serum concentration of Eliglustat can be increased when it is combined with Desipramine.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Eliglustat.
DiltiazemThe serum concentration of Eliglustat can be increased when it is combined with Diltiazem.
DiphenhydramineThe serum concentration of Eliglustat can be increased when it is combined with Diphenhydramine.
DofetilideDofetilide may increase the QTc-prolonging activities of Eliglustat.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Eliglustat.
DuloxetineThe serum concentration of Eliglustat can be increased when it is combined with Duloxetine.
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Eliglustat.
EnzalutamideThe serum concentration of Eliglustat can be decreased when it is combined with Enzalutamide.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Eliglustat.
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Eliglustat.
FluconazoleThe serum concentration of Eliglustat can be increased when it is combined with Fluconazole.
FluoxetineThe serum concentration of Eliglustat can be increased when it is combined with Fluoxetine.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Eliglustat.
FosamprenavirThe serum concentration of Eliglustat can be increased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Eliglustat can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Eliglustat can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Eliglustat can be increased when it is combined with Fusidic Acid.
GoserelinGoserelin may increase the QTc-prolonging activities of Eliglustat.
IdelalisibThe serum concentration of Eliglustat can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Eliglustat can be increased when it is combined with Imatinib.
ImipramineThe serum concentration of Eliglustat can be increased when it is combined with Imipramine.
IndinavirThe serum concentration of Eliglustat can be increased when it is combined with Indinavir.
IsavuconazoniumThe serum concentration of Eliglustat can be increased when it is combined with Isavuconazonium.
IsoniazidThe serum concentration of Eliglustat can be increased when it is combined with Isoniazid.
ItraconazoleThe serum concentration of Eliglustat can be increased when it is combined with Itraconazole.
IvabradineIvabradine may increase the QTc-prolonging activities of Eliglustat.
IvacaftorThe serum concentration of Eliglustat can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Eliglustat can be increased when it is combined with Ketoconazole.
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Eliglustat.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Eliglustat.
LorcaserinThe serum concentration of Eliglustat can be increased when it is combined with Lorcaserin.
LuliconazoleThe serum concentration of Eliglustat can be increased when it is combined with Luliconazole.
MethotrimeprazineThe serum concentration of Eliglustat can be increased when it is combined with Methotrimeprazine.
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Eliglustat.
MifepristoneMifepristone may increase the QTc-prolonging activities of Eliglustat.
MirabegronThe serum concentration of Eliglustat can be increased when it is combined with Mirabegron.
MitotaneThe serum concentration of Eliglustat can be decreased when it is combined with Mitotane.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Eliglustat.
NebivololThe serum concentration of Nebivolol can be increased when it is combined with Eliglustat.
NefazodoneThe serum concentration of Eliglustat can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Eliglustat can be increased when it is combined with Nelfinavir.
NicardipineThe serum concentration of Eliglustat can be increased when it is combined with Nicardipine.
OctreotideOctreotide may increase the QTc-prolonging activities of Eliglustat.
PalbociclibThe serum concentration of Eliglustat can be increased when it is combined with Palbociclib.
ParoxetineThe serum concentration of Eliglustat can be increased when it is combined with Paroxetine.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Eliglustat.
Peginterferon alfa-2bThe serum concentration of Eliglustat can be decreased when it is combined with Peginterferon alfa-2b.
PhenobarbitalThe serum concentration of Eliglustat can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Eliglustat can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Eliglustat can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Eliglustat can be decreased when it is combined with Primidone.
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Eliglustat.
RifabutinThe serum concentration of Eliglustat can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Eliglustat can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Eliglustat can be decreased when it is combined with Rifapentine.
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Eliglustat.
RitonavirThe serum concentration of Eliglustat can be increased when it is combined with Ritonavir.
RolapitantThe serum concentration of Eliglustat can be increased when it is combined with Rolapitant.
SaquinavirThe serum concentration of Saquinavir can be increased when it is combined with Eliglustat.
SertralineThe serum concentration of Eliglustat can be increased when it is combined with Sertraline.
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Eliglustat.
SiltuximabThe serum concentration of Eliglustat can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Eliglustat can be increased when it is combined with Simeprevir.
St. John's WortThe serum concentration of Eliglustat can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Eliglustat can be increased when it is combined with Stiripentol.
TamoxifenThe serum concentration of the active metabolites of Tamoxifen can be reduced when Tamoxifen is used in combination with Eliglustat resulting in a loss in efficacy.
TelaprevirThe serum concentration of Eliglustat can be increased when it is combined with Telaprevir.
TerbinafineThe serum concentration of Eliglustat can be increased when it is combined with Terbinafine.
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Eliglustat.
TiclopidineThe serum concentration of Eliglustat can be increased when it is combined with Ticlopidine.
TipranavirThe serum concentration of Eliglustat can be increased when it is combined with Tipranavir.
TocilizumabThe serum concentration of Eliglustat can be decreased when it is combined with Tocilizumab.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Eliglustat.
TramadolThe therapeutic efficacy of Tramadol can be decreased when used in combination with Eliglustat.
TranylcypromineThe serum concentration of Eliglustat can be increased when it is combined with Tranylcypromine.
VerapamilThe serum concentration of Eliglustat can be increased when it is combined with Verapamil.
VincristineThe serum concentration of Vincristine can be increased when it is combined with Eliglustat.
VoriconazoleThe serum concentration of Eliglustat can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Ceramide glucosyltransferase activity
Specific Function:
Catalyzes the first glycosylation step in glycosphingolipid biosynthesis, the transfer of glucose to ceramide. May also serve as a "flippase".
Gene Name:
UGCG
Uniprot ID:
Q16739
Molecular Weight:
44853.255 Da
References
  1. Poole RM: Eliglustat: first global approval. Drugs. 2014 Oct;74(15):1829-36. doi: 10.1007/s40265-014-0296-3. [PubMed:25239269 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Poole RM: Eliglustat: first global approval. Drugs. 2014 Oct;74(15):1829-36. doi: 10.1007/s40265-014-0296-3. [PubMed:25239269 ]
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Poole RM: Eliglustat: first global approval. Drugs. 2014 Oct;74(15):1829-36. doi: 10.1007/s40265-014-0296-3. [PubMed:25239269 ]
Comments
comments powered by Disqus
Drug created on April 02, 2015 10:54 / Updated on August 24, 2016 01:52