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

Stem definition	Drug id	CAS RN
enzyme inhibitors	1807	72599-27-0

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
0.30	g	O

ADMET properties:

Property	Value	Reference
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:

Date	Agency	Company	Orphan
Nov. 20, 2002	EMA
July 31, 2003	FDA	ACTELION PHARMS LTD

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Niemann-Pick disease	421.06	39.50	44	1184	6	53347832
Seizure	139.92	39.50	65	1163	129444	53218394
Dysphagia	68.59	39.50	35	1193	84362	53263476
Gastrostomy	62.58	39.50	11	1217	587	53347251
Epilepsy	61.93	39.50	23	1205	25744	53322094
Disease progression	59.66	39.50	34	1194	101886	53245952
Tremor	58.10	39.50	36	1192	125700	53222138
Diarrhoea	56.39	39.50	70	1158	625476	52722362
Weight decreased	47.98	39.50	41	1187	234907	53112931
Pneumonia aspiration	45.58	39.50	20	1208	34281	53313557
Gastrointestinal tube insertion	43.39	39.50	9	1219	1158	53346680
Concomitant disease aggravated	41.46	39.50	13	1215	8725	53339113

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Niemann-Pick disease	368.85	41.78	42	1165	23	32512296
Seizure	121.19	41.78	64	1143	103790	32408529
Gastrostomy	78.78	41.78	15	1192	770	32511549
Concomitant disease aggravated	58.03	41.78	17	1190	5636	32506683
Disease progression	49.71	41.78	34	1173	86828	32425491
Diarrhoea	48.43	41.78	63	1144	364739	32147580
Pneumonia aspiration	46.63	41.78	25	1182	41131	32471188

Pharmacologic Action:

Source	Code	Description
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-HIV agents

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Ceramide glucosyltransferase	Enzyme	Q16739	CEGT_HUMAN	INHIBITOR	Ki	5.13	IUPHAR	CHEMBL
Lysosomal alpha-glucosidase	Enzyme	P10253	LYAG_HUMAN		IC50	7	CHEMBL
Non-lysosomal glucosylceramidase	Enzyme	Q9HCG7	GBA2_HUMAN		IC50	6.64	CHEMBL
Sucrase-isomaltase, intestinal	Enzyme	P14410	SUIS_HUMAN		IC50	6.30	CHEMBL
Glycogen debranching enzyme	Enzyme	P35573	GDE_HUMAN		IC50	5	CHEMBL
Maltase-glucoamylase, intestinal	Enzyme	O43451	MGA_HUMAN		IC50	5.68	CHEMBL
Sucrase-isomaltase, intestinal	Enzyme		SUIS_RAT		IC50	6.24	CHEMBL
Non-lysosomal glucosylceramidase	Enzyme		GBA2_MOUSE		IC50	6.85	CHEMBL
Lysosomal alpha-glucosidase	Enzyme		LYAG_RAT		IC50	5.68	CHEMBL
Lysosomal alpha-glucosidase	Enzyme		LYAG_MOUSE		IC50	5.05	CHEMBL
Sucrase-isomaltase	Enzyme		B5THE3_MOUSE		IC50	6.22	CHEMBL
Putative alpha-glucosidase	Enzyme		Q9LGC6_ORYSJ		IC50	6.38	CHEMBL
Trehalase	Enzyme		O70282_RAT		IC50	4.89	CHEMBL
Uncharacterized protein	Enzyme		I3LIR5_PIG		IC50	4.44	CHEMBL
Ceramide glucosyltransferase	Enzyme		CEGT_MOUSE		IC50	4.64	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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