miglustat 🐶 Veterinary Use | 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 µM/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
Seizure 153.11 38.54 66 1152 132568 63355236
Dysphagia 73.04 38.54 35 1183 88550 63399254
Tremor 65.19 38.54 37 1181 132202 63355602
Epilepsy 64.92 38.54 23 1195 27042 63460762
Gastrostomy 63.27 38.54 11 1207 663 63487141
Diarrhoea 60.80 38.54 71 1147 715295 62772509
Disease progression 59.54 38.54 34 1184 122724 63365080
Pneumonia aspiration 48.96 38.54 20 1198 34520 63453284
Weight decreased 48.64 38.54 41 1177 276757 63211047
Gastrointestinal tube insertion 45.34 38.54 9 1209 1118 63486686
Concomitant disease aggravated 43.26 38.54 13 1205 9099 63478705
GM2 gangliosidosis 39.45 38.54 4 1214 0 63487804

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
Seizure 128.39 41.85 65 1133 104792 34850941
Gastrostomy 80.11 41.85 15 1183 763 34954970
Concomitant disease aggravated 59.24 41.85 17 1181 5684 34950049
Pneumonia aspiration 50.99 41.85 26 1172 41877 34913856
Diarrhoea 50.71 41.85 64 1134 389848 34565885
Disease progression 45.47 41.85 34 1164 108043 34847690
Epilepsy 43.63 41.85 19 1179 21476 34934257

FDA Adverse Event Reporting System (Geriatric)

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
Seizure 258.55 37.41 121 2259 188713 79553295
Gastrostomy 132.48 37.41 24 2356 1169 79740839
Concomitant disease aggravated 100.63 37.41 30 2350 13137 79728871
Pneumonia aspiration 97.53 37.41 45 2335 66922 79675086
Dysphagia 90.35 37.41 52 2328 122084 79619924
Epilepsy 87.34 37.41 36 2344 40824 79701184
Disease progression 87.08 37.41 59 2321 184303 79557705
Diarrhoea 78.23 37.41 112 2268 880377 78861631
Tremor 69.88 37.41 50 2330 170033 79571975
Weight decreased 60.46 37.41 63 2317 355135 79386873
Tracheostomy 57.14 37.41 12 2368 1260 79740748
Cataplexy 54.81 37.41 11 2369 923 79741085
Neurological decompensation 53.62 37.41 15 2365 5238 79736770
Gastrointestinal tube insertion 48.71 37.41 11 2369 1619 79740389
Growth retardation 46.78 37.41 11 2369 1932 79740076
Ataxia 46.57 37.41 20 2360 25019 79716989
Product supply issue 41.06 37.41 10 2370 2038 79739970
Chitotriosidase increased 38.49 37.41 5 2375 23 79741985
Laryngotracheal operation 37.68 37.41 4 2376 0 79742008
GM2 gangliosidosis 37.68 37.41 4 2376 0 79742008

FDA Adverse Event Reporting System (Pediatric)

None

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
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
FDA EPC N0000175783 Glucosylceramide Synthase Inhibitor
CHEBI has role CHEBI:50382 glucosylceramide synthase inhibitors
CHEBI has role CHEBI:64946 anti-AIDS agent

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Niemann-Pick disease, type C indication 66751000
Glucosylceramide beta-glucosidase deficiency indication 190794006 DOID:1926
Lateonset Pompe disease indication 722343009
Impaired renal function disorder contraindication 197663003
Pregnancy, function contraindication 289908002
Peripheral nerve disease contraindication 302226006
Breastfeeding (mother) contraindication 413712001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
Lysosomal alpha-glucosidase Enzyme IC50 7 CHEMBL
Non-lysosomal glucosylceramidase Enzyme IC50 6.64 CHEMBL
Sucrase-isomaltase, intestinal Enzyme IC50 6.30 CHEMBL
Glycogen debranching enzyme Enzyme IC50 5 CHEMBL
Maltase-glucoamylase, intestinal Enzyme IC50 5.68 CHEMBL
Sucrase-isomaltase, intestinal Enzyme IC50 6.24 CHEMBL
Non-lysosomal glucosylceramidase Enzyme IC50 6.85 CHEMBL
Lysosomal alpha-glucosidase Enzyme IC50 5.68 CHEMBL
Lysosomal alpha-glucosidase Enzyme IC50 5.05 CHEMBL
Sucrase-isomaltase Enzyme IC50 6.22 CHEMBL
Putative alpha-glucosidase Enzyme IC50 6.38 CHEMBL
Trehalase Enzyme IC50 4.89 CHEMBL
Uncharacterized protein Enzyme IC50 4.44 CHEMBL
Ceramide glucosyltransferase Enzyme IC50 4.64 CHEMBL

External reference:

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

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 10148-201 CAPSULE 100 mg ORAL NDA AUTHORIZED GENERIC 29 sections
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
Yargesa Human Prescription Drug Label 1 42799-709 CAPSULE 100 mg ORAL ANDA 25 sections
MIGLUSTAT HUMAN PRESCRIPTION DRUG LABEL 1 43975-310 CAPSULE 100 mg ORAL ANDA 26 sections
miglustat HUMAN PRESCRIPTION DRUG LABEL 1 51991-959 CAPSULE 100 mg ORAL ANDA 29 sections
Zavesca HUMAN PRESCRIPTION DRUG LABEL 1 66215-201 CAPSULE 100 mg ORAL NDA 29 sections
Zavesca HUMAN PRESCRIPTION DRUG LABEL 1 66215-201 CAPSULE 100 mg ORAL NDA 29 sections
Zavesca HUMAN PRESCRIPTION DRUG LABEL 1 66215-201 CAPSULE 100 mg ORAL NDA 29 sections