U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H21NO4
Molecular Weight 219.2784
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIGLUSTAT

SMILES

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

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

1.0595232E12
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

1.0595232E12
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: Page: 918-001
unhealthy, 44
n = 28
Health Status: unhealthy
Condition: Gaucher disease
Age Group: 44
Sex: M+F
Population Size: 28
Sources: Page: 918-001
Disc. AE: Neuritis, Neuropathy...
AEs leading to
discontinuation/dose reduction:
Neuritis (grade 3-4)
Neuropathy (grade 3-4)
Sources: Page: 918-001
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: Page: 918-001
unhealthy, 44
n = 28
Health Status: unhealthy
Condition: Gaucher disease
Age Group: 44
Sex: M+F
Population Size: 28
Sources: Page: 918-001
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: Page: 918-001
unhealthy, 44
n = 28
Health Status: unhealthy
Condition: Gaucher disease
Age Group: 44
Sex: M+F
Population Size: 28
Sources: Page: 918-001
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
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
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model.
2002 May 20
The combination of interferon alpha-2b and n-butyl deoxynojirimycin has a greater than additive antiviral effect upon production of infectious bovine viral diarrhea virus (BVDV) in vitro: implications for hepatitis C virus (HCV) therapy.
2002 Sep
New therapeutics for the treatment of glycosphingolipid lysosomal storage diseases.
2003
Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1.
2003 Feb
[Drug for Gaucher disease also works as sperm inhibitor. Is the "pill" for the man on its way?].
2003 Feb 13
Gaucher disease and the clinical experience with substrate reduction therapy.
2003 May 29
Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease.
2003 May 29
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
Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick disease type C.
2004 Aug
New drugs of 2003.
2004 Mar-Apr
Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for the treatment of hepatitis C.
2004 May
Ceramide synthesis correlates with the posttranscriptional regulation of the sterol-regulatory element-binding protein.
2004 May
Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life.
2004 Sep 17
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
Synthesis and glycosidase inhibitory activity of new hexa-substituted C8-glycomimetics.
2005 Oct 7
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
Gangliosides do not affect ABC transporter function in human neuroblastoma cells.
2006 Jun
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
Substrate deprivation therapy: a new hope for patients suffering from neuronopathic forms of inherited lysosomal storage diseases.
2007
[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
Neurologic improvement in a type 3 Gaucher disease patient treated with imiglucerase/miglustat combination.
2007 Jul
[Is it possible to treat the brain? Recent advances in inherited neurodegenerative disorders].
2007 Mar
Selective action of the iminosugar isofagomine, a pharmacological chaperone for mutant forms of acid-beta-glucosidase.
2007 May 1
[Cost reduction in the treatment of Gaucher s disease].
2007 May-Jun
[Osteoarticular manifestations of Gaucher disease in adults: pathophysiology and treatment].
2007 Oct
Treatment of Niemann-Pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year.
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
Motion analysis of a child with Niemann-Pick disease type C treated with miglustat.
2008 Jan
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
1,5-(BUTYLIMINO)-1,5 DIDEOXY,D-GLUCITOL
Common 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
OGT 918
Code English
MIGLUSTAT [WHO-DD]
Common Name English
N-BUTYLDEOXYNOJIRIMYCIN
Common Name English
OGT-918
Code English
MIGLUSTAT [MI]
Common Name English
MIGLUSTAT [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 756020
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
FDA ORPHAN DRUG 270708
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
EMA ASSESSMENT REPORTS ZAVESCA (AUTHORIZED: NIEMANN-PICK DISEASE)
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
WHO-ATC A16AX06
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
FDA ORPHAN DRUG 798620
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
NDF-RT N0000020019
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
EMA ASSESSMENT REPORTS ZAVESCA (AUTHORIZED: GAUCHER DISEASE)
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
EMA ASSESSMENT REPORTS ZAVESCA (AUTHORIZED: NIEMANN-PICK DISEASES)
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
NCI_THESAURUS C2846
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
FDA ORPHAN DRUG 795420
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
EU-Orphan Drug EU/3/06/351
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
NDF-RT N0000175783
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
FDA ORPHAN DRUG 112198
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
WHO-VATC QA16AX06
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
FDA ORPHAN DRUG 601617
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
FDA ORPHAN DRUG 112598
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C1222
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
PUBCHEM
51634
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
LACTMED
Miglustat
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
IUPHAR
4841
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
EVMPD
SUB20049
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
INN
8138
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
RXCUI
402316
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY RxNorm
CAS
72599-27-0
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
ChEMBL
CHEMBL1029
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
MERCK INDEX
M7538
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY Merck Index
EPA CompTox
72599-27-0
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
DRUG CENTRAL
1807
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
DRUG BANK
DB00419
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
FDA UNII
ADN3S497AZ
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY
MESH
C059896
Created by admin on Fri Jun 25 21:31:04 UTC 2021 , Edited by admin on Fri Jun 25 21:31:04 UTC 2021
PRIMARY