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
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
Molecular Formula | C10H21NO4 |
Molecular Weight | 219.278 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB00419Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/cdi/miglustat.html
Sources: http://www.drugbank.ca/drugs/DB00419
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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2063 Sources: http://www.drugbank.ca/drugs/DB00419 |
|||
Target ID: CHEMBL2074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7608901 |
2.1 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Zavesca Approved UseGaucher 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 Date1.0595232E12 |
|||
Primary | Zavesca Approved UseGaucher 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 Date1.0595232E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1328 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17720777 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17720777 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10868 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17720777 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17720777 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17720777 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17720777 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
100% |
MIGLUSTAT plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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) Sources: Page: 918-001Neuropathy (grade 3-4) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-348_Zavesca_BioPharmr.pdf#page=15 Page: 15.0 |
no |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. | 2002 May 20 |
|
Imino sugars that are less toxic but more potent as antivirals, in vitro, compared with N-n-nonyl DNJ. | 2002 Sep |
|
Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1. | 2003 Feb |
|
Gateways to clinical trials. | 2003 May |
|
Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease. | 2003 May 29 |
|
Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick disease type C. | 2004 Aug |
|
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 |
|
Computerized cognitive testing in patients with type I Gaucher disease: effects of enzyme replacement and substrate reduction. | 2005 Feb |
|
Gangliosides do not affect ABC transporter function in human neuroblastoma cells. | 2006 Jun |
|
Therapeutic goals in Gaucher disease. | 2006 Mar |
|
Long-term non-hormonal male contraception in mice using N-butyldeoxynojirimycin. | 2006 May |
|
Emerging strategies for the treatment of hereditary metabolic storage disorders. | 2006 Summer |
|
[Niemann-Pick diseases in adults]. | 2007 Dec |
|
Selective action of the iminosugar isofagomine, a pharmacological chaperone for mutant forms of acid-beta-glucosidase. | 2007 May 1 |
|
Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. | 2007 Oct |
|
Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease. | 2008 Mar |
|
Gaucher disease. | 2008 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/miglustat.html
100 mg orally 3 times a day at regular intervals
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14580684
50 uM Miglustat reduced MEB4 cell GlcCer synthase activity (by 70%), ganglioside synthesis (by 61%), and shedding (by 37%)
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:28:52 UTC 2023
by
admin
on
Fri Dec 15 15:28:52 UTC 2023
|
Record UNII |
ADN3S497AZ
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
756020
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
FDA ORPHAN DRUG |
270708
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
EMA ASSESSMENT REPORTS |
ZAVESCA (AUTHORIZED: NIEMANN-PICK DISEASE)
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
WHO-ATC |
A16AX06
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
FDA ORPHAN DRUG |
798620
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
NDF-RT |
N0000020019
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
EMA ASSESSMENT REPORTS |
ZAVESCA (AUTHORIZED: GAUCHER DISEASE)
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
EMA ASSESSMENT REPORTS |
ZAVESCA (AUTHORIZED: NIEMANN-PICK DISEASES)
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
NCI_THESAURUS |
C2846
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
FDA ORPHAN DRUG |
795420
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
EU-Orphan Drug |
EU/3/06/351
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
NDF-RT |
N0000175783
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
FDA ORPHAN DRUG |
112198
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
WHO-VATC |
QA16AX06
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
FDA ORPHAN DRUG |
601617
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
||
|
FDA ORPHAN DRUG |
112598
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
C1222
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
51634
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
Miglustat
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
50381
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
4841
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
Miglustat
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
SUB20049
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
100000089526
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
PP-68
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
8138
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
402316
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | RxNorm | ||
|
72599-27-0
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
CHEMBL1029
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
m7538
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | Merck Index | ||
|
DTXSID6045618
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
1807
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
DB00419
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
ADN3S497AZ
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
ADN3S497AZ
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY | |||
|
C059896
Created by
admin on Fri Dec 15 15:28:52 UTC 2023 , Edited by admin on Fri Dec 15 15:28:52 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
BINDER->LIGAND |
Miglustat does not bind to plasma proteins.
|
||
|
TARGET -> INHIBITOR |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
|
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Tmax | PHARMACOKINETIC |
|
in Gaucher patients |
|
||
Biological Half-life | PHARMACOKINETIC |
|
|
|||
Volume of Distribution | PHARMACOKINETIC |
|
in Gaucher patients |
|
||