miglustat Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
enzyme inhibitors 1807 72599-27-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • miglustat
  • N-Butyldeoxynojirimycin
  • N-Butylmoranoline
  • zavesca
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. Miglustat helps 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). In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids.
  • Molecular weight: 219.28
  • Formula: C10H21NO4
  • CLOGP: 0.91
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 4
  • TPSA: 84.16
  • ALOGS: 0.18
  • ROTB: 4

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.30 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1000 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 85 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 19.54 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 97 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
Nov. 20, 2002 EMA
July 31, 2003 FDA ACTELION PHARMS LTD

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Niemann-Pick disease 416.52 40.50 44 1148 6 46684864
Seizure 121.50 40.50 60 1132 122994 46561876
Dysphagia 68.07 40.50 35 1157 77277 46607593
Gastrostomy 61.88 40.50 11 1181 564 46684306
Disease progression 59.88 40.50 34 1158 91266 46593604
Epilepsy 57.82 40.50 22 1170 23716 46661154
Tremor 57.45 40.50 36 1156 115603 46569267
Diarrhoea 50.44 40.50 66 1126 559536 46125334
Weight decreased 48.16 40.50 41 1151 210808 46474062
Pneumonia aspiration 45.17 40.50 20 1172 31585 46653285
Gastrointestinal tube insertion 42.80 40.50 9 1183 1114 46683756
Concomitant disease aggravated 41.46 40.50 13 1179 7869 46677001

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Niemann-Pick disease 358.94 44.73 41 1093 23 29951321
Seizure 109.04 44.73 59 1075 98416 29852928
Gastrostomy 79.45 44.73 15 1119 721 29950623
Concomitant disease aggravated 59.35 44.73 17 1117 5112 29946232
Disease progression 51.72 44.73 34 1100 79840 29871504
Diarrhoea 45.48 44.73 59 1075 334044 29617300

Pharmacologic Action:

SourceCodeDescription
ATC A16AX06 ALIMENTARY TRACT AND METABOLISM
OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
Various alimentary tract and metabolism products
FDA MoA N0000020019 Glucosylceramide Synthase Inhibitors
FDA EPC N0000175783 Glucosylceramide Synthase Inhibitor
MeSH PA D019380 Anti-HIV Agents
MeSH PA D000890 Anti-Infective Agents
MeSH PA D044966 Anti-Retroviral Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D065089 Glycoside Hydrolase Inhibitors
MeSH PA D007004 Hypoglycemic Agents
CHEBI has role CHEBI:50382 glucosylceramide synthase inhibitors
CHEBI has role CHEBI:64946 anti-hiv agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Niemann-Pick disease, type C indication 66751000
Glucosylceramide beta-glucosidase deficiency indication 190794006 DOID:1926
Impaired renal function disorder contraindication 197663003
Pregnancy, function contraindication 289908002
Peripheral nerve disease contraindication 302226006
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.42 acidic
pKa2 7.76 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Ceramide glucosyltransferase Enzyme INHIBITOR Ki 5.13 IUPHAR CHEMBL
Maltase-glucoamylase, intestinal Enzyme IC50 5.68 CHEMBL
Glycogen debranching enzyme Enzyme IC50 5 CHEMBL
Lysosomal alpha-glucosidase Enzyme IC50 7 CHEMBL
Non-lysosomal glucosylceramidase Enzyme IC50 6.64 CHEMBL
Sucrase-isomaltase, intestinal Enzyme IC50 6.30 CHEMBL
Lysosomal alpha-glucosidase Enzyme IC50 5.68 CHEMBL
Trehalase Unclassified IC50 4.89 CHEMBL
Uncharacterized protein Unclassified IC50 4.44 CHEMBL
Sucrase-isomaltase, intestinal Enzyme IC50 6.24 CHEMBL
Non-lysosomal glucosylceramidase Enzyme IC50 6.85 CHEMBL
Putative alpha-glucosidase Enzyme IC50 6.38 CHEMBL
Sucrase-isomaltase Enzyme IC50 6.22 CHEMBL
Lysosomal alpha-glucosidase Enzyme IC50 5.05 CHEMBL
Ceramide glucosyltransferase Unclassified IC50 4.64 CHEMBL

External reference:

IDSource
4021406 VUID
N0000148822 NUI
D05032 KEGG_DRUG
4021406 VANDF
C1321596 UMLSCUI
CHEBI:50381 CHEBI
NBV PDB_CHEM_ID
CHEMBL1029 ChEMBL_ID
DB00419 DRUGBANK_ID
C059896 MESH_SUPPLEMENTAL_RECORD_UI
4841 IUPHAR_LIGAND_ID
8138 INN_ID
ADN3S497AZ UNII
51634 PUBCHEM_CID
356766 RXNORM
17531 MMSL
276708 MMSL
47238 MMSL
d04889 MMSL
009940 NDDF
408044003 SNOMEDCT_US
412296005 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Miglustat HUMAN PRESCRIPTION DRUG LABEL 1 10148-201 CAPSULE 100 mg ORAL NDA AUTHORIZED GENERIC 29 sections
Miglustat Human Prescription Drug Label 1 42799-708 CAPSULE 100 mg ORAL ANDA 23 sections
MIGLUSTAT HUMAN PRESCRIPTION DRUG LABEL 1 43975-310 CAPSULE 100 mg ORAL ANDA 26 sections
Zavesca HUMAN PRESCRIPTION DRUG LABEL 1 66215-201 CAPSULE 100 mg ORAL NDA 29 sections