miglustat 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.491 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.631 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.382 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 1.324 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 85.400 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 75.120 % High 1
herg hERG pIC50 4.503 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.276 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.027 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 79.440 % High 1
kinase-safety-class ACVR2A,ACVR2B,AXL,BRAF,CAMK2D,CDK4,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,GRK2,ITK,MAP2K6,MAP3K21,MAPK10,MAPK7,NTRK2,PDK2,PDK4,PRKDC,TEK,TGFBR1,ZAP70 24
kinase-selectivity-class ACVRL1,AXL,CDK1,CDK2,CDK4,CDK6,CDK7,CDK9,CHUK,DYRK1A,EIF2AK3,EPHB4,IGF1R,INSR,IRAK1,IRAK3,IRAK4,MAP2K6,MAP3K14,PIK3CD,TEK,TGFBR1,ZAP70 23
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.280 High 1
mh-clint Mouse hepatocyte intrinsic clearance 1.059 High 1
mppb Mouse plasma protein binding (% unbound) 89.180 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.552 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 88.210 % High 1
rh-clint Rat hepatocyte intrinsic clearance 0.975 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 88.310 % High 1
rppb Rat plasma protein binding (% unbound) 87.240 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 901.571 uM High 1

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 166.20 40.47 67 1230 152562 90474588
Dysphagia 78.00 40.47 36 1261 112242 90514908
Tremor 75.99 40.47 39 1258 153134 90474016
Disease progression 63.85 40.47 35 1262 156580 90470570
Gastrostomy 63.67 40.47 11 1286 860 90626290
Diarrhoea 61.92 40.47 71 1226 939119 89688031
Pneumonia aspiration 54.91 40.47 21 1276 40919 90586231
Gastrointestinal tube insertion 52.62 40.47 10 1287 1330 90625820
Weight decreased 51.91 40.47 43 1254 379867 90247283
Epilepsy 46.74 40.47 23 1274 82183 90544967
Concomitant disease aggravated 44.01 40.47 13 1284 11505 90615645
GM2 gangliosidosis 40.62 40.47 4 1293 0 90627150

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 136.76 40.89 68 1211 120493 42499563
Gastrostomy 85.50 40.89 16 1263 929 42619127
Concomitant disease aggravated 59.04 40.89 17 1262 6569 42613487
Diarrhoea 50.47 40.89 65 1214 460784 42159272
Pneumonia aspiration 49.86 40.89 26 1253 50052 42570004
Disease progression 47.28 40.89 37 1242 143619 42476437
Epilepsy 42.45 40.89 19 1260 26152 42593904

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 282.03 36.06 124 2376 221061 110365738
Gastrostomy 139.41 36.06 25 2475 1525 110585274
Pneumonia aspiration 104.39 36.06 46 2454 81187 110505612
Concomitant disease aggravated 102.42 36.06 30 2470 16334 110570465
Dysphagia 100.95 36.06 55 2445 153545 110433254
Disease progression 96.61 36.06 63 2437 243971 110342828
Diarrhoea 84.44 36.06 115 2385 1139390 109447409
Tremor 79.46 36.06 52 2448 202180 110384619
Epilepsy 66.06 36.06 36 2464 100173 110486626
Weight decreased 66.02 36.06 66 2434 467991 110118808
Tracheostomy 58.28 36.06 12 2488 1515 110585284
Growth retardation 57.37 36.06 13 2487 2569 110584230
Cataplexy 55.40 36.06 11 2489 1158 110585641
Gastrointestinal tube insertion 54.46 36.06 12 2488 2089 110584710
Neurological decompensation 53.73 36.06 15 2485 6868 110579931
Ataxia 48.37 36.06 20 2480 30088 110556711
Chitotriosidase increased 39.37 36.06 5 2495 26 110586773
Laryngotracheal operation 38.79 36.06 4 2496 0 110586799
GM2 gangliosidosis 38.79 36.06 4 2496 0 110586799
Product supply issue 37.71 36.06 10 2490 3776 110583023

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 D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D007004 Hypoglycemic Agents
MeSH PA D019380 Anti-HIV Agents
MeSH PA D044966 Anti-Retroviral Agents
MeSH PA D065089 Glycoside Hydrolase Inhibitors
FDA EPC N0000175783 Glucosylceramide Synthase Inhibitor
FDA EPC N0000194077 Enzyme Stabilizer
FDA MoA N0000194078 Enzyme Stabilizers
CHEBI has role CHEBI:50382 EC 2.4.1.80 (ceramide glucosyltransferase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

A16AX Various alimentary tract and metabolism products 23 drugs
anethole trithionedoxecitinedoxribtimineeliglustatfosdenopteringivosiranglycerol phenylbutyratelonafarniblumasiranmigalastatnedosirannitisinone show all 23 →

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 10512677 March 7, 2033 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 11278599 March 7, 2033 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 12419937 March 7, 2033 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 10208299 Sept. 30, 2035 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 10961522 Sept. 30, 2035 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 11753632 Sept. 30, 2035 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 11278601 Dec. 29, 2036 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 12414985 Dec. 29, 2036 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 10857212 Aug. 12, 2037 THE TREATMENT OF POMPE PATIENTS
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL 12246062 Sept. 16, 2038 THE TREATMENT OF POMPE PATIENTS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
65MG OPFOLDA AMICUS THERAP US N215211 Sept. 28, 2023 RX CAPSULE ORAL Sept. 28, 2026 NEW PRODUCT

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
ADN3S497AZ INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Miglustat HUMAN PRESCRIPTION DRUG LABEL 1 10148-201 CAPSULE 100 mg ORAL NDA authorized generic 29 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
Zavesca HUMAN PRESCRIPTION DRUG LABEL 1 66215-201 CAPSULE 100 mg ORAL NDA 29 sections
Miglustat HUMAN PRESCRIPTION DRUG LABEL 1 68475-204 CAPSULE 100 mg ORAL ANDA 22 sections
Miglustat HUMAN PRESCRIPTION DRUG LABEL 1 70710-2039 CAPSULE 100 mg ORAL ANDA 22 sections
OPFOLDA HUMAN PRESCRIPTION DRUG LABEL 1 71904-300 CAPSULE 65 mg ORAL NDA 26 sections