miglustat ๐Ÿถ 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 ยตM/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 144.55 37.64 65 1124 117809 50486126
Dysphagia 70.74 37.64 35 1154 77483 50526452
Epilepsy 65.47 37.64 23 1166 21544 50582391
Gastrostomy 63.77 37.64 11 1178 515 50603420
Tremor 63.06 37.64 37 1152 114866 50489069
Disease progression 60.97 37.64 34 1155 95832 50508103
Diarrhoea 60.40 37.64 71 1118 588405 50015530
Weight decreased 49.42 37.64 41 1148 221204 50382731
Pneumonia aspiration 47.14 37.64 20 1169 30984 50572951
Gastrointestinal tube insertion 44.51 37.64 9 1180 1000 50602935
Concomitant disease aggravated 42.19 37.64 13 1176 8078 50595857
GM2 gangliosidosis 38.64 37.64 4 1185 0 50603935

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 124.36 41.42 64 1099 93059 29480305
Gastrostomy 80.61 41.42 15 1148 641 29572723
Concomitant disease aggravated 59.21 41.42 17 1146 4961 29568403
Diarrhoea 50.21 41.42 63 1100 332635 29240729
Disease progression 49.76 41.42 34 1129 81882 29491482
Pneumonia aspiration 47.96 41.42 25 1138 36712 29536652
Epilepsy 43.93 41.42 19 1144 18413 29554951

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 247.68 36.99 120 2212 166772 64329628
Gastrostomy 132.26 36.99 24 2308 970 64495430
Concomitant disease aggravated 98.86 36.99 30 2302 11512 64484888
Pneumonia aspiration 91.49 36.99 44 2288 59227 64437173
Disease progression 90.94 36.99 59 2273 141621 64354779
Dysphagia 87.57 36.99 52 2280 106760 64389640
Epilepsy 87.55 36.99 36 2296 33495 64462905
Diarrhoea 77.27 36.99 111 2221 722593 63773807
Tremor 67.45 36.99 50 2282 148180 64348220
Weight decreased 61.84 36.99 63 2269 285676 64210724
Tracheostomy 56.37 36.99 12 2320 1108 64495292
Neurological decompensation 53.28 36.99 15 2317 4421 64491979
Cataplexy 48.13 36.99 10 2322 821 64495579
Gastrointestinal tube insertion 47.71 36.99 11 2321 1463 64494937
Growth retardation 47.08 36.99 11 2321 1550 64494850
Ataxia 45.29 36.99 20 2312 22064 64474336
Product supply issue 43.08 36.99 10 2322 1369 64495031
Condition aggravated 39.12 36.99 57 2275 372369 64124031

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 (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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ 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
NBV PDB_CHEM_ID
CHEMBL1029 ChEMBL_ID
DB00419 DRUGBANK_ID
51634 PUBCHEM_CID
8138 INN_ID
C059896 MESH_SUPPLEMENTAL_RECORD_UI
4841 IUPHAR_LIGAND_ID
ADN3S497AZ UNII
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
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