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Accession NumberDB00419  (APRD01118)
TypeSmall Molecule

Miglustat is a drug used to treat Gaucher disease. It inhibits the enzyme glucosylceramide synthase, an essential enzyme for the synthesis of most glycosphingolipids. It is only used for patients who cannot be treated with enzyme replacement therapy with imiglucerase. Miglustat is marketed under the trade name Zavesca. Miglustat is now the first and only approved therapy for patients with Niemann-Pick disease type C (NP-C). It has recently been approved for treatment of progressive neurological symptoms in adult and pediatric patients in the European Union, Brazil, and South Korea. Miglustat was first developed as an anti-HIV agent in the 1990s. However, clinical experience with miglustat showed that therapeutic levels of the drug could not be achieved in patients without a high incidence of adverse effect.

N-Butyl deoxynojirimycin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zavescacapsule100 mg/1oralActelion Pharmaceuticals US, Inc.2003-07-31Not applicableUs
Zavescacapsule100 mgoralActelion Pharmaceuticals Ltd2004-05-26Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Miglustat Hydrochloride
  • Monoisotopic Mass: 219.147058165
  • Average Mass: 219.278
CAS number72599-27-0
WeightAverage: 219.278
Monoisotopic: 219.147058165
Chemical FormulaC10H21NO4
CCCCN1C[[email protected]](O)[C@@H](O)[[email protected]](O)[[email protected]]1CO
DescriptionThis compound belongs to the class of organic compounds known as piperidines. These are compounds containing a piperidine ring, which is a saturated aliphatic six-member ring with one nitrogen atom and five carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
Sub ClassNot Available
Direct ParentPiperidines
Alternative Parents
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Polyol
  • 1,2-diol
  • 1,2-aminoalcohol
  • Azacycle
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
IndicationFor the treatment of adult patients with mild to moderate type 1 (nonneuropathic) Gaucher's disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to constraints such as allergy, hypersensitivity, or poor venous access). Now approved in some countries for the treatment of progressive neurological symptoms in adult and pediatric patients with Niemann-Pick disease type C (NP-C).
PharmacodynamicsMiglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures.
Mechanism of actionMiglustat 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. The goal of treatment with miglustat is to 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), reducing the accumulation of glucocerebroside in macrophages. In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids. In clinical trials, miglustat improved liver and spleen volume, as well as hemoglobin concentration and platelet count. Inhibition of glycosphingolipid synthesis has also shown to reduce intracellular lipid storage, improve fluid-phase endosomal uptake and normalize lipid transport in peripheral blood B lymphocytes of NP-C patients, which results in a decrease in the potentially neurotoxic accumulation of gnagliosides GM2 and GM3, lactosylceramide and glucosylceramide, possibly preventing further neuronal damage. Other studies have also suggested that miglustat may indirectly modulate intracellular calcium homeostasis through its effects on glucosylceramide levels, and evidence has shown that an initiating factor in the pathogenesis of NP-C may be impaired calcium homeostasis related to sphingosine storage. Therefore, the effect that miglustat exerts on intracellular calcium levels may influence an important underlying pathogenic mechanism of NP-C.
Related Articles
AbsorptionMean oral bioavailability is 97%.
Volume of distributionNot Available
Protein bindingMiglustat does not bind to plasma proteins.

There is no evidence that miglustat is metabolized in humans.

Route of eliminationNot Available
Half lifeThe effective half-life of miglustat is approximately 6 to 7 hours.
ClearanceNot Available
ToxicityMiglustat has been administered at doses of up to 3000 mg/day (approximately 10 times the recommended starting dose administered to Gaucher patients) for up to six months in Human Immunodeficiency Virus (HIV)-positive patients. Adverse events observed in the HIV studies included granulocytopenia, dizziness, and paresthesia. Leukopenia and neutropenia have also been observed in a similar group of patients receiving 800 mg/day or above.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Predicted ADMET features
Human Intestinal Absorption+0.9092
Blood Brain Barrier-0.9011
Caco-2 permeable-0.6433
P-glycoprotein substrateSubstrate0.8088
P-glycoprotein inhibitor INon-inhibitor0.667
P-glycoprotein inhibitor IINon-inhibitor0.9556
Renal organic cation transporterNon-inhibitor0.757
CYP450 2C9 substrateNon-substrate0.8224
CYP450 2D6 substrateNon-substrate0.765
CYP450 3A4 substrateNon-substrate0.5817
CYP450 1A2 substrateNon-inhibitor0.9188
CYP450 2C9 inhibitorNon-inhibitor0.8855
CYP450 2D6 inhibitorNon-inhibitor0.9226
CYP450 2C19 inhibitorNon-inhibitor0.9484
CYP450 3A4 inhibitorNon-inhibitor0.9855
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9941
Ames testNon AMES toxic0.8426
BiodegradationNot ready biodegradable0.5763
Rat acute toxicity2.1203 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6675
hERG inhibition (predictor II)Non-inhibitor0.8508
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
  • Actelion pharmaceuticals ltd
Dosage forms
Capsuleoral100 mg/1
Capsuleoral100 mg
Unit descriptionCostUnit
Zavesca 100 mg capsule160.67USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5472969 No1993-05-132013-05-13Us
US5525616 No1993-06-112013-06-11Us
Experimental Properties
melting point169-172 °CNot Available
water solubilityHighly soluble in water (>1000 mg/mL as a free base).Not Available
logP-0.6Not Available
Predicted Properties
Water Solubility331.0 mg/mLALOGPS
pKa (Strongest Acidic)12.9ChemAxon
pKa (Strongest Basic)8.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area84.16 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity55.74 m3·mol-1ChemAxon
Polarizability23.99 Å3ChemAxon
Number of Rings1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Mass Spec (NIST)Not Available
SpectraNot Available
Synthesis ReferenceNot Available
General References
  1. van Giersbergen PL, Dingemanse J: Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. J Clin Pharmacol. 2007 Oct;47(10):1277-82. Epub 2007 Aug 24. [PubMed:17720777 ]
  2. Weinreb NJ, Barranger JA, Charrow J, Grabowski GA, Mankin HJ, Mistry P: Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol. 2005 Nov;80(3):223-9. [PubMed:16247743 ]
  3. Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE: Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol. 2007 Sep;6(9):765-72. [PubMed:17689147 ]
  4. Moyses C: Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease. Philos Trans R Soc Lond B Biol Sci. 2003 May 29;358(1433):955-60. [PubMed:12803929 ]
  5. Wraith JE, Imrie J: New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag. 2009;5:877-87. Epub 2009 Nov 18. [PubMed:19956552 ]
  6. McCormack PL, Goa KL: Miglustat. Drugs. 2003;63(22):2427-34; discussion 2435-6. [PubMed:14609352 ]
External Links
ATC CodesA16AX06
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (911 KB)
MSDSNot Available
Drug InteractionsNo interactions found.
Food InteractionsNot Available


Pharmacological action
General Function:
Ceramide glucosyltransferase activity
Specific Function:
Catalyzes the first glycosylation step in glycosphingolipid biosynthesis, the transfer of glucose to ceramide. May also serve as a "flippase".
Gene Name:
Uniprot ID:
Molecular Weight:
44853.255 Da
  1. Moyses C: Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease. Philos Trans R Soc Lond B Biol Sci. 2003 May 29;358(1433):955-60. [PubMed:12803929 ]
  2. Weinreb NJ, Barranger JA, Charrow J, Grabowski GA, Mankin HJ, Mistry P: Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol. 2005 Nov;80(3):223-9. [PubMed:16247743 ]
  3. Chien YH, Lee NC, Tsai LK, Huang AC, Peng SF, Chen SJ, Hwu WL: Treatment of Niemann-Pick disease type C in two children with miglustat: initial responses and maintenance of effects over 1 year. J Inherit Metab Dis. 2007 Oct;30(5):826. Epub 2007 Jun 21. [PubMed:17603755 ]
  4. Treiber A, Morand O, Clozel M: The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat. Xenobiotica. 2007 Mar;37(3):298-314. [PubMed:17624027 ]
  5. Ficicioglu C: Review of miglustat for clinical management in Gaucher disease type 1. Ther Clin Risk Manag. 2008 Apr;4(2):425-31. [PubMed:18728838 ]
  6. Wraith JE, Imrie J: New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat. Ther Clin Risk Manag. 2009;5:877-87. Epub 2009 Nov 18. [PubMed:19956552 ]
  7. Pastores GM: Miglustat: substrate reduction therapy for lysosomal storage disorders associated with primary central nervous system involvement. Recent Pat CNS Drug Discov. 2006 Jan;1(1):77-82. [PubMed:18221193 ]
  8. McCormack PL, Goa KL: Miglustat. Drugs. 2003;63(22):2427-34; discussion 2435-6. [PubMed:14609352 ]
  9. Giraldo P, Latre P, Alfonso P, Acedo A, Alonso D, Barez A, Corrales A, Franco R, Roldan V, Serrano S, Pocovi M: Short-term effect of miglustat in every day clinical use in treatment-naive or previously treated patients with type 1 Gaucher's disease. Haematologica. 2006 May;91(5):703-6. Epub 2006 Apr 19. [PubMed:16627252 ]
  10. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on November 20, 2013 14:54