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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H21NO4
Molecular Weight 219.278
Optical Activity ( - )
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Miglustat

SMILES

CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO

InChI

InChIKey=UQRORFVVSGFNRO-UTINFBMNSA-N
InChI=1S/C10H21NO4/c1-2-3-4-11-5-8(13)10(15)9(14)7(11)6-12/h7-10,12-15H,2-6H2,1H3/t7-,8+,9-,10-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/miglustat.html

Miglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures. Miglustat functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids. The goal of treatment with miglustat is to reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to a level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy), reducing the accumulation of glucocerebroside in macrophages. In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids. In clinical trials, miglustat improved liver and spleen volume, as well as hemoglobin concentration and platelet count. Inhibition of glycosphingolipid synthesis has also shown to reduce intracellular lipid storage, improve fluid-phase endosomal uptake and normalize lipid transport in peripheral blood B lymphocytes of NP-C patients, which results in a decrease in the potentially neurotoxic accumulation of gnagliosides GM2 and GM3, lactosylceramide and glucosylceramide, possibly preventing further neuronal damage. Other studies have also suggested that miglustat may indirectly modulate intracellular calcium homeostasis through its effects on glucosylceramide levels, and evidence has shown that an initiating factor in the pathogenesis of NP-C may be impaired calcium homeostasis related to sphingosine storage. Therefore, the effect that miglustat exerts on intracellular calcium levels may influence an important underlying pathogenic mechanism of NP-C. Miglustat is used for the treatment of adult patients with mild to moderate type 1 (nonneuropathic) Gaucher's disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to constraints such as allergy, hypersensitivity, or poor venous access). Now approved in some countries for the treatment of progressive neurological symptoms in adult and pediatric patients with Niemann-Pick disease type C (NP-C). Miglustat is marketed under the trade name Zavesca.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.1 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Zavesca

Approved Use

Gaucher disease: Treatment of adult patients with mild-to-moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (eg, due to allergy, hypersensitivity, or poor venous access) Canadian labeling: Additional use (not in U.S. labeling): Treatment to delay the progression of neurological manifestations in Niemann-Pick type C disease

Launch Date

2003
Primary
Zavesca

Approved Use

Gaucher disease: Treatment of adult patients with mild-to-moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (eg, due to allergy, hypersensitivity, or poor venous access) Canadian labeling: Additional use (not in U.S. labeling): Treatment to delay the progression of neurological manifestations in Niemann-Pick type C disease

Launch Date

2003
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1328 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIGLUSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
843 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIGLUSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10868 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIGLUSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9320 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIGLUSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.8 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIGLUSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIGLUSTAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
MIGLUSTAT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 44
Disc. AE: Neuritis, Neuropathy...
AEs leading to
discontinuation/dose reduction:
Neuritis (grade 3-4)
Neuropathy (grade 3-4)
Sources:
AEs

AEs

AESignificanceDosePopulation
Neuritis grade 3-4
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 44
Neuropathy grade 3-4
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, 44
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely
no
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
PubMed

PubMed

TitleDatePubMed
6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs.
1991 Jun
Inhibition of HIV and SIV infectivity by blockade of alpha-glucosidase activity.
1991 Mar
Differential effects of glycolipid biosynthesis inhibitors on ceramide-induced cell death in neuroblastoma cells.
1999 Mar
N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours.
2001 Apr 20
Critical role for glycosphingolipids in Niemann-Pick disease type C.
2001 Aug 21
Substrate reduction therapy for glycosphingolipid storage disorders.
2001 Mar
Regulation of apoptosis during neuronal differentiation by ceramide and b-series complex gangliosides.
2001 Nov 30
pH-sensitive liposomes are efficient carriers for endoplasmic reticulum-targeted drugs in mouse melanoma cells.
2002 May 10
Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human CD1d heavy chain.
2002 Nov 22
Miglustat. Oxford GlycoSciences/Actelion.
2003 Apr
Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease.
2004
[Type 1 Gaucher's disease in the adult. Nutritional management during initiation of treatment with miglustat].
2004 Apr 10
C-glycosides and aza-C-glycosides as potential glycosidase and glycosyltransferase inhibitors.
2005
An open-label, noncomparative study of miglustat in type I Gaucher disease: efficacy and tolerability over 24 months of treatment.
2005 Aug
Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors.
2005 Aug 16
Guidance on the use of miglustat for treating patients with type 1 Gaucher disease.
2005 Nov
Miglustat: new drug. In type 1 Gaucher's disease : a slight benefit after imiglucerase therapy.
2005 Oct
Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses.
2005 Oct
Synthesis and glycosidase inhibitory activity of new hexa-substituted C8-glycomimetics.
2005 Oct 7
Miglustat (NB-DNJ) works as a chaperone for mutated acid beta-glucosidase in cells transfected with several Gaucher disease mutations.
2005 Sep-Oct
Gaucher disease: multiple lessons from a single gene disorder.
2006 Apr
D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains.
2006 Apr 11
Rescue of functional delF508-CFTR channels in cystic fibrosis epithelial cells by the alpha-glucosidase inhibitor miglustat.
2006 Apr 3
Substrate reduction therapy of glycosphingolipid storage disorders.
2006 Apr-Jun
Inhibition of hybrid- and complex-type glycosylation reveals the presence of the GlcNAc transferase I-independent fucosylation pathway.
2006 Aug
Miglustat: substrate reduction therapy for lysosomal storage disorders associated with primary central nervous system involvement.
2006 Jan
Miglustat: substrate reduction therapy for glycosphingolipid lysosomal storage disorders.
2006 Jan
Substrate reduction therapy in the infantile form of Tay-Sachs disease.
2006 Jan 24
Gateways to clinical trials.
2006 Jan-Feb
Gangliosides do not affect ABC transporter function in human neuroblastoma cells.
2006 Jun
Therapeutic goals in Gaucher disease.
2006 Mar
[Clinical study of the French cohort of Gaucher disease patients].
2006 Mar
Short-term effect of miglustat in every day clinical use in treatment-naïve or previously treated patients with type 1 Gaucher's disease.
2006 May
Long-term non-hormonal male contraception in mice using N-butyldeoxynojirimycin.
2006 May
Clinical experience with substrate reduction therapy.
2006 Nov
Effective treatment of an elderly patient with Gaucher's disease and Parkinsonism: a case report of 24 months' oral substrate reduction therapy with miglustat.
2007 Aug
[Osteoarticular manifestations of Gaucher disease in adults: pathophysiology and treatment].
2007 Dec
[Iminosugars: current and future therapeutic applications].
2007 Jan
The sensitivity of murine spermiogenesis to miglustat is a quantitative trait: a pharmacogenetic study.
2007 Jan 22
Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolism.
2007 Jun
The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat.
2007 Mar
[Organization of Gaucher disease management in France].
2007 Oct
[Therapeutic objectives in Gaucher disease].
2007 Oct
Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement.
2007 Oct 1
Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease.
2007 Sep
Gaucher disease: improving management.
2008 Apr
Proteasome-dependent pharmacological rescue of cystic fibrosis transmembrane conductance regulator revealed by mutation of glycine 622.
2008 Apr
N-butyldeoxynojirimycin causes weight loss as a result of appetite suppression in lean and obese mice.
2008 Feb
Parallel improvement of sodium and chloride transport defects by miglustat (n-butyldeoxynojyrimicin) in cystic fibrosis epithelial cells.
2008 Jun
Patents

Patents

Sample Use Guides

100 mg orally 3 times a day at regular intervals
Route of Administration: Oral
50 uM Miglustat reduced MEB4 cell GlcCer synthase activity (by 70%), ganglioside synthesis (by 61%), and shedding (by 37%)
Name Type Language
Miglustat
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
OPFOLDA
Preferred Name English
3,4,5-Piperidinetriol, 1-butyl-2-(hydroxymethyl)-, (2R,3R,4R,5S)-
Systematic Name English
(2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)piperidine-3,4,5-triol
Systematic Name English
MIGLUSTAT [ORANGE BOOK]
Common Name English
MIGLUSTAT [EMA EPAR]
Common Name English
MIGLUSTAT [MART.]
Common Name English
MIGLUSTAT [VANDF]
Common Name English
ZAVESCA
Brand Name English
MIGLUSTAT [JAN]
Common Name English
MIGLUSTAT [USAN]
Common Name English
BUTYLDEOXYNOJIRIMYCIN
Common Name English
(2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)-3,4,5-piperidinetriol
Systematic Name English
N-BUTYLDEOXYNOJIRIMYCIN
Common Name English
OGT-918
Code English
1,5-(BUTYLIMINO)-1,5-DIDEOXY-D-GLUCITOL
Common Name English
Miglustat [WHO-DD]
Common Name English
MIGLUSTAT [MI]
Common Name English
miglustat [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 756020
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
FDA ORPHAN DRUG 270708
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
EMA ASSESSMENT REPORTS ZAVESCA (AUTHORIZED: NIEMANN-PICK DISEASE)
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
WHO-ATC A16AX06
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
FDA ORPHAN DRUG 798620
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
NDF-RT N0000020019
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
EMA ASSESSMENT REPORTS ZAVESCA (AUTHORIZED: GAUCHER DISEASE)
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
EMA ASSESSMENT REPORTS ZAVESCA (AUTHORIZED: NIEMANN-PICK DISEASES)
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
NCI_THESAURUS C2846
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
FDA ORPHAN DRUG 795420
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
EU-Orphan Drug EU/3/06/351
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
NDF-RT N0000175783
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
FDA ORPHAN DRUG 112198
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
WHO-VATC QA16AX06
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
FDA ORPHAN DRUG 601617
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
FDA ORPHAN DRUG 112598
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C1222
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
PUBCHEM
51634
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
LACTMED
Miglustat
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
CHEBI
50381
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
IUPHAR
4841
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
WIKIPEDIA
Miglustat
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
EVMPD
SUB20049
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
SMS_ID
100000089526
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
USAN
PP-68
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
INN
8138
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
RXCUI
402316
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY RxNorm
CAS
72599-27-0
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
ChEMBL
CHEMBL1029
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
MERCK INDEX
m7538
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY Merck Index
EPA CompTox
DTXSID6045618
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
DRUG CENTRAL
1807
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
DRUG BANK
DB00419
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
FDA UNII
ADN3S497AZ
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
DAILYMED
ADN3S497AZ
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY
MESH
C059896
Created by admin on Mon Mar 31 17:58:33 GMT 2025 , Edited by admin on Mon Mar 31 17:58:33 GMT 2025
PRIMARY