Miglustat hydrochloride | OGT-918 | Zavesca | CAS#72599-27-0 | CAS#210110-90-0

MedKoo Cat#: 510249 | Name: Miglustat HCl

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Miglustat, also known as OGT 918 and NB-DNJ, is a drug developed by Actelion and is used primarily to treat Type I Gaucher disease (GD1). Miglustat inhibits glucosylceramide synthase, an essential enzyme for the synthesis of most glycosphingolipids (it forms glucosylceramide and accumulates within the macrophages). Miglustat is used to treat adults with mild-to-moderate Type I Gaucher disease and it is the first treatment to be approved for patients with NiemannÂ–Pick type C disease

Chemical Structure

Miglustat HCl

CAS#210110-90-0 (HCl)

Theoretical Analysis

MedKoo Cat#: 510249

Name: Miglustat HCl

CAS#: 210110-90-0 (HCl)

Chemical Formula: C10H21NO4

Exact Mass: 0.0000

Molecular Weight: 255.74

Elemental Analysis: C, 46.96; H, 8.67; Cl, 13.86; N, 5.48; O, 25.02

Price and Availability

Size	Price	Availability
25mg	USD 350.00	2 weeks
50mg	USD 650.00	2 weeks
100mg	USD 950.00	2 Weeks

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Related CAS #

72599-27-0 (free base) 210110-90-0 (HCl)

Synonym

OGT918; OGT 918; OGT-918; Miglustat; N-butyldeoxynojirimycin; NB-DNJ; Miglustat hydrochloride; Brand name: Zavesca.

IUPAC/Chemical Name

(2R,3R,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride

InChi Key

QPAFAUYWVZMWPR-ZSOUGHPYSA-N

InChi Code

InChI=1S/C10H21NO4.ClH/c1-2-3-4-11-5-8(13)10(15)9(14)7(11)6-12;/h7-10,12-15H,2-6H2,1H3;1H/t7-,8+,9-,10-;/m1./s1

SMILES Code

O[C@@H]1[C@@H](CO)N(CCCC)C[C@H](O)[C@H]1O.[H]Cl

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

0 Â– 4 C for short term (weeks to 1 month) or -20 C for long terms (months to years).

Solubility

Soluble in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in water

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Miglustat may only be used in the treatment of Type I Gaucher patients for whom enzyme replacement therapy is unsuitable and it's been approved in the European Union for the treatment of progressive neurological manifestations in adult or pediatric patients with NiemannÂ–Pick type C disease (NPC). It has also been approved for NPC treatment in Australia, Brazil, Canada, Israel, Russia, Switzerland and Turkey but not in the United States. (copied from http://en.wikipedia.org/wiki/Miglustat). The primary pharmacological activity of miglustat is inhibition of the enzyme glucosylceramide synthase, catalyzing the first step in the biosynthesis of glycosphingolipids (GSL), i.e., the formation of glucosylceramide (GlcCer). Reduced formation of GlcCer will lead to decreased biosynthesis of more complex GSL. This therapeutic principle, called substrate reduction therapy (SRT), may be useful in disorders of intracellular (predominantly lysosomal) accumulation of GSL either due to their deficient breakdown or intracellular transport/trafficking. Miglustat exhibits a large volume of distribution and has the capacity to access deep organs such as the brain, bone and lung. (copied from http://en.wikipedia.org/wiki/Miglustat).

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Miglustat (N-Butyldeoxynojirimycin) hydrochloride is an orally active ceramide glucosyltransferase inhibitor.

In vitro activity:

This study reports that in human airway epithelial CF15 cells treated with the CFTR corrector miglustat (n-butyldeoxynojyrimicin), whole-cell patch-clamp experiments showed reduced amiloride-sensitive ENaC current in parallel with a rescue of defective CFTR Cl- channel activity activated by forskolin and genistein. Reference: J Pharmacol Exp Ther. 2008 Jun;325(3):1016-23. https://pubmed.ncbi.nlm.nih.gov/18309088/

In vivo activity:

To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis, followed by combined CCl4 plus miglustat for a further 2 weeks. Miglustat dose-dependently downregulated expression of α-smooth muscle actin and ECM components in TGF-β-treated HHSteCs. Both phosphorylation and nuclear translocation of Smad2 and Smad3 were also suppressed by miglustat treatment. Reference: Biochem Biophys Res Commun. 2023 Jan 29;642:192-200. https://pubmed.ncbi.nlm.nih.gov/36586187/

	Solvent	mg/mL	mM
Solubility
	Water	26.6	103.97

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 255.74 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Noël S, Wilke M, Bot AG, De Jonge HR, Becq F. Parallel improvement of sodium and chloride transport defects by miglustat (n-butyldeoxynojyrimicin) in cystic fibrosis epithelial cells. J Pharmacol Exp Ther. 2008 Jun;325(3):1016-23. doi: 10.1124/jpet.107.135582. Epub 2008 Feb 28. PMID: 18309088. 2. Girard MC, Sacerdoti F, Rivera FP, Repetto HA, Ibarra C, Amaral MM. Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells. Toxicon. 2015 Oct;105:27-33. doi: 10.1016/j.toxicon.2015.08.021. Epub 2015 Aug 31. PMID: 26335361. 3. Iwanaga T, Chiba T, Nakamura M, Kaneko T, Ao J, Qiang N, Ma Y, Zhang J, Kogure T, Yumita S, Ishino T, Ogawa K, Kan M, Nakagawa M, Fujiwara K, Fujita N, Sakuma T, Kanzaki H, Koroki K, Kusakabe Y, Inoue M, Kobayashi K, Kanogawa N, Kiyono S, Kondo T, Nakagawa R, Ogasawara S, Nakamoto S, Muroyama R, Kato J, Kanda T, Maruyama H, Mimura N, Honda T, Murayama T, Nakamura H, Kato N. Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-β/Smad pathway suppression in hepatic stellate cells. Biochem Biophys Res Commun. 2023 Jan 29;642:192-200. doi: 10.1016/j.bbrc.2022.12.025. Epub 2022 Dec 10. PMID: 36586187. 4. D'Arcangelo G, Grossi D, Racaniello M, Cardinale A, Zaratti A, Rufini S, Cutarelli A, Tancredi V, Merlo D, Frank C. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease. Neural Plast. 2016;2016:3830424. doi: 10.1155/2016/3830424. Epub 2016 Jan 14. PMID: 26885401; PMCID: PMC4738957.

In vitro protocol:

In vivo protocol:

1. Iwanaga T, Chiba T, Nakamura M, Kaneko T, Ao J, Qiang N, Ma Y, Zhang J, Kogure T, Yumita S, Ishino T, Ogawa K, Kan M, Nakagawa M, Fujiwara K, Fujita N, Sakuma T, Kanzaki H, Koroki K, Kusakabe Y, Inoue M, Kobayashi K, Kanogawa N, Kiyono S, Kondo T, Nakagawa R, Ogasawara S, Nakamoto S, Muroyama R, Kato J, Kanda T, Maruyama H, Mimura N, Honda T, Murayama T, Nakamura H, Kato N. Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-β/Smad pathway suppression in hepatic stellate cells. Biochem Biophys Res Commun. 2023 Jan 29;642:192-200. doi: 10.1016/j.bbrc.2022.12.025. Epub 2022 Dec 10. PMID: 36586187. 2. D'Arcangelo G, Grossi D, Racaniello M, Cardinale A, Zaratti A, Rufini S, Cutarelli A, Tancredi V, Merlo D, Frank C. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease. Neural Plast. 2016;2016:3830424. doi: 10.1155/2016/3830424. Epub 2016 Jan 14. PMID: 26885401; PMCID: PMC4738957.

1: Kitatani T, Takahashi S, Ikenoya S. [Pharmacological and clinical profiles of miglustat (Brazaves(Â®)) for the treatment of Niemann-Pick type C disease]. Nihon Yakurigaku Zasshi. 2013 Mar;141(3):160-7. Review. Japanese. PubMed PMID: 23470482. 2: Walterfang M, Chien YH, Imrie J, Rushton D, Schubiger D, Patterson MC. Dysphagia as a risk factor for mortality in Niemann-Pick disease type C: systematic literature review and evidence from studies with miglustat. Orphanet J Rare Dis. 2012 Oct 6;7:76. doi: 10.1186/1750-1172-7-76. Review. PubMed PMID: 23039766; PubMed Central PMCID: PMC3552828. 3: Venier RE, Igdoura SA. Miglustat as a therapeutic agent: prospects and caveats. J Med Genet. 2012 Sep;49(9):591-7. doi: 10.1136/jmedgenet-2012-101070. Epub 2012 Aug 14. Review. PubMed PMID: 22892202. 4: Belmatoug N, Burlina A, Giraldo P, Hendriksz CJ, Kuter DJ, Mengel E, Pastores GM. Gastrointestinal disturbances and their management in miglustat-treated patients. J Inherit Metab Dis. 2011 Oct;34(5):991-1001. doi: 10.1007/s10545-011-9368-7. Epub 2011 Jul 21. Review. PubMed PMID: 21779792. 5: Pastores GM, Giraldo P, ChÃ©rin P, Mehta A. Goal-oriented therapy with miglustat in Gaucher disease. Curr Med Res Opin. 2009 Jan;25(1):23-37. doi: 10.1185/03007990802576518 . Review. PubMed PMID: 19210136. 6: 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. Review. PubMed PMID: 18221193. 7: Lachmann RH. Miglustat: substrate reduction therapy for glycosphingolipid lysosomal storage disorders. Drugs Today (Barc). 2006 Jan;42(1):29-38. Review. PubMed PMID: 16511609. 8: 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. Review. PubMed PMID: 16247743. 9: McCormack PL, Goa KL. Miglustat. Drugs. 2003;63(22):2427-34; discussion 2435-6. Review. PubMed PMID: 14609352. 10: Cox TM, Aerts JM, Andria G, Beck M, Belmatoug N, Bembi B, Chertkoff R, Vom Dahl S, Elstein D, Erikson A, Giralt M, Heitner R, Hollak C, Hrebicek M, Lewis S, Mehta A, Pastores GM, Rolfs A, Miranda MC, Zimran A; Advisory Council to the European Working Group on Gaucher Disease. The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement. J Inherit Metab Dis. 2003;26(6):513-26. Review. PubMed PMID: 14605497. 11: Lachmann RH. Miglustat. Oxford GlycoSciences/Actelion. Curr Opin Investig Drugs. 2003 Apr;4(4):472-9. Review. PubMed PMID: 12808890. 12: Pastores GM, Barnett NL. Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1. Expert Opin Investig Drugs. 2003 Feb;12(2):273-81. Review. PubMed PMID: 12556220.