1 deoxynojirimycin


Summary: An alpha-glucosidase inhibitor with antiviral action. Derivatives of deoxynojirimycin may have anti-HIV activity.

Top Publications

  1. Hamanaka R, Shinohara T, Yano S, Nakamura M, Yasuda A, Yokoyama S, et al. Rescue of mutant alpha-galactosidase A in the endoplasmic reticulum by 1-deoxygalactonojirimycin leads to trafficking to lysosomes. Biochim Biophys Acta. 2008;1782:408-13 pubmed publisher
    ..These data suggest that the rescue of R301Q from ERAD is a key step for normalization of intracellular trafficking of R301Q. ..
  2. Walden C, Butters T, Dwek R, Platt F, van der Spoel A. Long-term non-hormonal male contraception in mice using N-butyldeoxynojirimycin. Hum Reprod. 2006;21:1309-15 pubmed
    ..Low-dose treatment with NB-DNJ over a long period is an effective approach for the regulation of fertility in a male mammal by non-hormonal means, without causing overt adverse effects. ..
  3. Pineda M, Perez Poyato M, O CALLAGHAN M, Vilaseca M, Pocovi M, Domingo R, et al. Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series. Mol Genet Metab. 2010;99:358-66 pubmed publisher
    ..Overall, miglustat appeared to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic benefits appeared smaller among younger patients who were at a more advanced stage of disease at baseline...
  4. Jeyakumar M, Thomas R, Elliot Smith E, Smith D, van der Spoel A, d Azzo A, et al. Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain. 2003;126:974-87 pubmed
    ..These data suggest that inflammation may play an important role in the pathogenesis of the gangliosidoses...
  5. Okumiya T, Kroos M, Vliet L, Takeuchi H, Van der Ploeg A, Reuser A. Chemical chaperones improve transport and enhance stability of mutant alpha-glucosidases in glycogen storage disease type II. Mol Genet Metab. 2007;90:49-57 pubmed
    ..Chemical chaperone therapy could create new perspectives for therapeutic intervention in GSDII. ..
  6. Suganuma R, Walden C, Butters T, Platt F, Dwek R, Yanagimachi R, et al. Alkylated imino sugars, reversible male infertility-inducing agents, do not affect the genetic integrity of male mouse germ cells during short-term treatment despite induction of sperm deformities. Biol Reprod. 2005;72:805-13 pubmed
    ..This indicates that during short-term administration, alkylated imino sugars alter sperm morphology and physiology but do not diminish the genetic potential of spermatozoa. ..
  7. Treiber A, Morand O, Clozel M. The pharmacokinetics and tissue distribution of the glucosylceramide synthase inhibitor miglustat in the rat. Xenobiotica. 2007;37:298-314 pubmed
    ..Miglustat was eliminated via renal clearance by a combination of glomerular filtration and active secretion. Hepatic clearance was negligible, as was the role of metabolism in the overall elimination process of miglustat in the rat. ..
  8. Zervas M, Somers K, Thrall M, Walkley S. Critical role for glycosphingolipids in Niemann-Pick disease type C. Curr Biol. 2001;11:1283-7 pubmed
  9. Patterson M, Vecchio D, Jacklin E, Abel L, Chadha Boreham H, Luzy C, et al. Long-term miglustat therapy in children with Niemann-Pick disease type C. J Child Neurol. 2010;25:300-5 pubmed publisher
    ..Miglustat stabilized neurological disease progression in pediatric patients with Niemann-Pick disease type C, with comparable safety and tolerability to that observed in adults and juveniles...

More Information


  1. Fan J, Ishii S, Asano N, Suzuki Y. Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nat Med. 1999;5:112-5 pubmed
    ..We propose a new molecular therapeutic strategy for genetic metabolic diseases of administering competitive inhibitors as 'chemical chaperons' at sub-inhibitory intracellular concentrations. ..
  2. Aerts J, Ottenhoff R, Powlson A, Grefhorst A, van Eijk M, Dubbelhuis P, et al. Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity. Diabetes. 2007;56:1341-9 pubmed
  3. Patterson M, Vecchio D, Prady H, Abel L, Wraith J. Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol. 2007;6:765-72 pubmed
    ..Miglustat improves or stabilises several clinically relevant markers of NPC. This is the first agent studied in NPC for which there is both animal and clinical data supporting a disease modifying benefit. ..
  4. Mellor H, Nolan J, Pickering L, Wormald M, Platt F, Dwek R, et al. Preparation, biochemical characterization and biological properties of radiolabelled N-alkylated deoxynojirimycins. Biochem J. 2002;366:225-33 pubmed
    ..Overall these data provide further definition of the molecular features of alkylated imino sugars that influence tissue selectivity and efficacy for cellular enzyme inhibition. ..
  5. Davidson C, Ali N, Micsenyi M, Stephney G, Renault S, Dobrenis K, et al. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS ONE. 2009;4:e6951 pubmed publisher
    ..Understanding the mechanism(s) by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis. ..
  6. Galanaud D, Tourbah A, Lehericy S, Leveque N, Heron B, Billette De Villemeur T, et al. 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy. Mol Genet Metab. 2009;96:55-8 pubmed publisher
  7. Wraith J, Vecchio D, Jacklin E, Abel L, Chadha Boreham H, Luzy C, et al. Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial. Mol Genet Metab. 2010;99:351-7 pubmed publisher
    ..Overall, these data suggest that long-term miglustat therapy stabilizes neurological disease and is well tolerated in adult and juvenile patients with NP-C...
  8. Scheel M, Abegg M, Lanyon L, Mattman A, Barton J. Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient. Mol Genet Metab. 2010;99:291-5 pubmed publisher
    ..This method might be useful in future treatment trials for NPC to assess treatment effects. ..
  9. Pineda M, Wraith J, Mengel E, Sedel F, Hwu W, Rohrbach M, et al. Miglustat in patients with Niemann-Pick disease Type C (NP-C): a multicenter observational retrospective cohort study. Mol Genet Metab. 2009;98:243-9 pubmed publisher
    ..Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C. ..
  10. Shen C, Bullens D, Kasran A, Maerten P, Boon L, Aerts J, et al. Inhibition of glycolipid biosynthesis by N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin protects against the inflammatory response in hapten-induced colitis. Int Immunopharmacol. 2004;4:939-51 pubmed
    ..The data also provide evidence that glycolipid biosynthesis is involved in the inflammatory cascade in these inflammatory bowel disease (IBD) models. ..
  11. van der Spoel A, Jeyakumar M, Butters T, Charlton H, Moore H, Dwek R, et al. Reversible infertility in male mice after oral administration of alkylated imino sugars: a nonhormonal approach to male contraception. Proc Natl Acad Sci U S A. 2002;99:17173-8 pubmed
    ..These compounds therefore may be new leads in the development of a male contraceptive, especially because NB-DNJ has already been through extensive evaluation in various mammals, including man. ..
  12. Platt F, Jeyakumar M. Substrate reduction therapy. Acta Paediatr. 2008;97:88-93 pubmed publisher
    ..Furthermore, as SRT synergises with other therapeutic modalities, it may also prove to be a key component of combination therapies in the future. ..
  13. Chien Y, Lee N, Tsai L, Huang A, Peng S, Chen S, et al. 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;30:826 pubmed
    ..We conclude that miglustat can provide therapeutic benefits in CNS symptoms and allows stabilization of systemic disease in childhood-onset NP-C. Further follow-up is crucial to determine the long-term maintenance of these effects...
  14. Boucheron C, Toumieux S, Compain P, Martin O, Ikeda K, Asano N. Synthesis of 4-O-glycosylated 1-deoxynojirimycin derivatives as disaccharide mimics-based inhibitors of human beta-glucocerebrosidase. Carbohydr Res. 2007;342:1960-5 pubmed
  15. Bradbury F, Menon K. Retention of glucose on oligosaccharide chains linked to the LH/hCG receptor prevents cell surface expression. Biochem Biophys Res Commun. 2001;282:454-62 pubmed
    ..These results show that the removal of glucose residues is necessary for trafficking the LH/hCG receptor to the cell surface. ..
  16. Ruiz M, Ruanova T, Blanco O, Nuñez F, Pato C, Ojea V. Diastereoselective synthesis of piperidine imino sugars using aldol additions of metalated bislactim ethers to threose and erythrose acetonides. J Org Chem. 2008;73:2240-55 pubmed publisher
  17. Cai C, Rao L, Rao Y, Guo J, Xiao Z, Cao J, et al. Analogues of xanthones--Chalcones and bis-chalcones as ?-glucosidase inhibitors and anti-diabetes candidates. Eur J Med Chem. 2017;130:51-59 pubmed publisher
    ..Inspiringly, bis-chalcones 2g (at 1 ?M concentration) has stronger effect than 1-deoxynojirimycin on reducing the glucose level in HepG-2 cells (human liver cancer cell line). ..
  18. García Salom P, Acedo A. [Cost reduction in the treatment of Gaucher s disease]. Farm Hosp. 2007;31:194-5 pubmed
  19. Papandréou M, Barbouche R, Guieu R, Kieny M, Fenouillet E. The alpha-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step. Mol Pharmacol. 2002;61:186-93 pubmed
    ..Altogether, our results suggest that DNM and its analogs deserve further investigation as anti-HIV agents in combination with experimental compounds targeting CXCR4 to inhibit each partner of this crucial step of HIV entry. ..
  20. Miyake K, Nagai K. Inhibition of alpha-mannosidase attenuates endoplasmic reticulum stress-induced neuronal cell death. Neurotoxicology. 2009;30:144-50 pubmed publisher
    ..Our data suggests that inhibition of N-glycan processing in the ER attenuates ER stress-induced cell death by increasing high-mannose type oligosaccharides that reduce protein aggregation, such as amyloidogenesis. ..
  21. Bulow A, Plesner I, Bols M. Slow inhibition of almond beta-glucosidase by azasugars: determination of activation energies for slow binding. Biochim Biophys Acta. 2001;1545:207-15 pubmed
    ..1 J/molK. The large difference in DeltaS(0) of association of the different inhibitors suggests that the anomeric nitrogen atom of inhibitors 1-4 is involved in an interaction that results in a large entropy increase. ..
  22. Hu H, Shioda T, Moriya C, Xin X, Hasan M, Miyake K, et al. Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface. J Virol. 1996;70:7462-70 pubmed
    ..Thus, the sialylation catalyzed by host cell pathways appeared to reduce the infectivity of human and nonhuman primate lentiviruses. Our results further suggested that desialylation would help increase the titers of HIV-based vectors. ..
  23. Weinreb N, Barranger J, Charrow J, Grabowski G, Mankin H, Mistry P. Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol. 2005;80:223-9 pubmed
  24. Flanagan J, Rossi B, Tang K, Wu X, Mascioli K, Donaudy F, et al. The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Hum Mutat. 2009;30:1683-92 pubmed publisher
    ..Taken together, these data support further evaluation of DNJ as a potential treatment for Pompe disease in patients that express responsive forms of GAA. ..
  25. Yam G, Zuber C, Roth J. A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder. FASEB J. 2005;19:12-8 pubmed
    ..Small molecule chemical chaperones will be therapeutically useful for various lysosomal storage disorders as well as for other genetic metabolic disorders caused by mutant but nonetheless catalytically active enzymes. ..
  26. Nakagawa K, Ogawa K, Higuchi O, Kimura T, Miyazawa T, Hori M. Determination of iminosugars in mulberry leaves and silkworms using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Biochem. 2010;404:217-22 pubmed publisher
    ..g., different amounts of iminosugars in mulberry leaf varieties; high DNJ and low GAL-DNJ in the silkworm body, especially in the blood) that is useful for producing iminosugar-rich products for nutraceutical purposes. ..
  27. Alfonso P, Pampín S, Estrada J, Rodriguez Rey J, Giraldo P, Sancho J, et al. Miglustat (NB-DNJ) works as a chaperone for mutated acid beta-glucosidase in cells transfected with several Gaucher disease mutations. Blood Cells Mol Dis. 2005;35:268-76 pubmed
  28. Deppenmeier U, Hoffmeister M, Prust C. Biochemistry and biotechnological applications of Gluconobacter strains. Appl Microbiol Biotechnol. 2002;60:233-42 pubmed
    ..This uniqueness makes them ideal organisms for microbial process development...
  29. Lazar C, Durantel D, Macovei A, Zitzmann N, Zoulim F, Dwek R, et al. Treatment of hepatitis B virus-infected cells with alpha-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity. Antiviral Res. 2007;76:30-7 pubmed
    ..Our data show for the first time that an active alpha-glucosidase activity is crucial for production of infectious HBV and provide new insights into the controversial role of the M protein in this process. ..
  30. Zamoner L, Aragão Leoneti V, Mantoani S, Rugen M, Nepogodiev S, Field R, et al. CuAAC click chemistry with N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol provides access to triazole-linked piperidine and azepane pseudo-disaccharide iminosugars displaying glycosidase inhibitory proper. Carbohydr Res. 2016;429:29-37 pubmed publisher
    ..The greater activity of the piperidine could be rationalized based on docking studies. Further, potent inhibition of ?-amylase was observed with compounds from both the piperidine and azepane series. ..
  31. Dierking E, Bilyeu K. Raffinose and stachyose metabolism are not required for efficient soybean seed germination. J Plant Physiol. 2009;166:1329-35 pubmed publisher
    ..We conclude that RFOs are not an essential source of energy during soybean seed germination. ..
  32. Liang T, Liu S, Wang F, Gu J, Lu Y, Chen W, et al. A UPLC-MS/MS method for simultaneous determination of 1-deoxynojirimycin and N-methyl-1-deoxynojirimycin in rat plasma and its application in pharmacokinetic and absolute bioavailability studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1072:205-210 pubmed publisher
    ..The results of this study might provide more information on preclinical pharmacokinetics and a solid basis for assessing the clinical efficacy of DNJ and N-CH3-DNJ. ..
  33. Yuan K, Listinsky C, Singh R, Listinsky J, Siegal G. Cell surface associated alpha-L-fucose moieties modulate human breast cancer neoplastic progression. Pathol Oncol Res. 2008;14:145-56 pubmed publisher
    ..Further elucidation of the molecular pathways involved in the inhibition of tumor cell invasion may suggest a rationale for the use of glycobiologic therapeutics to deter tumor progression. ..
  34. Cox T. Substrate reduction therapy for lysosomal storage diseases. Acta Paediatr Suppl. 2005;94:69-75; discussion 57 pubmed
    ..The results of ongoing clinical trials of miglustat in type 3 Gaucher disease, Niemann-Pick disease type C and GM2 gangliosidosis are eagerly awaited. ..
  35. Marques A, Gabriel T, Aten J, van Roomen C, Ottenhoff R, Claessen N, et al. Gpnmb Is a Potential Marker for the Visceral Pathology in Niemann-Pick Type C Disease. PLoS ONE. 2016;11:e0147208 pubmed publisher
    ..In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation. ..
  36. Santacruz Tinoco C, Villagomez Castro J, Lopez Romero E. Entamoeba histolytica: identification and partial characterization of alpha-mannosidase activity. Exp Parasitol. 2010;124:459-65 pubmed publisher
    ..Results are discussed in terms of the possible identity of alpha-mannosidase activity and the potential precursor-product relationship between the two enzyme forms. ..
  37. Mellor H, Neville D, Harvey D, Platt F, Dwek R, Butters T. Cellular effects of deoxynojirimycin analogues: inhibition of N-linked oligosaccharide processing and generation of free glucosylated oligosaccharides. Biochem J. 2004;381:867-75 pubmed
    ..This represents the most detailed characterization of the FOS structures arising from ER a-glucosidase inhibition to date. ..
  38. Lehrman M, Zeng Y. Pleiotropic resistance to glycoprotein processing inhibitors in Chinese hamster ovary cells. The role of a novel mutation in the asparagine-linked glycosylation pathway. J Biol Chem. 1989;264:1584-93 pubmed
    ..We propose that this phenotype be termed PIR, for processing inhibitor resistance...
  39. Chabrol B. [Therapies in the Niemann-Pick type C disease]. Arch Pediatr. 2010;17 Suppl 2:S54-7 pubmed publisher
    ..Recently, the use of miglustat allows a number of cases of disease stabilization. The onset of treatment and monitoring will be the best in a reference center expert in the disease. ..
  40. Brumshtein B, Greenblatt H, Butters T, Shaaltiel Y, Aviezer D, Silman I, et al. Crystal structures of complexes of N-butyl- and N-nonyl-deoxynojirimycin bound to acid beta-glucosidase: insights into the mechanism of chemical chaperone action in Gaucher disease. J Biol Chem. 2007;282:29052-8 pubmed
    ..Together, these results have significance for understanding the mechanism of action of GlcCerase and the mode of GlcCerase chaperoning by imino sugars. ..
  41. Chippington S, McHugh K, Vellodi A. Splenic nodules in paediatric Gaucher disease treated by enzyme replacement therapy. Pediatr Radiol. 2008;38:657-60 pubmed publisher
    ..Disappearance of focal splenic lesions in children with GD during follow-up has not been previously reported. The development of new focal splenic lesions in children with GD whilst on ERT has not been previously documented. ..
  42. Luan Z, Higaki K, Aguilar Moncayo M, Ninomiya H, Ohno K, García Moreno M, et al. Chaperone activity of bicyclic nojirimycin analogues for Gaucher mutations in comparison with N-(n-nonyl)deoxynojirimycin. Chembiochem. 2009;10:2780-92 pubmed publisher
  43. Makino A, Ishii K, Murate M, Hayakawa T, Suzuki Y, Suzuki M, et al. D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains. Biochemistry. 2006;45:4530-41 pubmed
    ..Altering cholesterol homeostasis by D-PDMP explains the unique characteristics of sensitizing multidrug resistant cells by this drug. ..
  44. Fantur K, Hofer D, Schitter G, Steiner A, Pabst B, Wrodnigg T, et al. DLHex-DGJ, a novel derivative of 1-deoxygalactonojirimycin with pharmacological chaperone activity in human G(M1)-gangliosidosis fibroblasts. Mol Genet Metab. 2010;100:262-8 pubmed publisher
    ..R201C and p.R201H, two further alleles, p.C230R and p.G438E, displayed significant sensitivity against DLHex-DGJ, with an increase of catalytic activity, and a normalization of transport and lysosomal processing of beta-Gal precursors. ..
  45. Salehi A, Lundquist I. Modulation of islet G-proteins, alpha-glucosidehydrolase inhibition and insulin release stimulated by various secretagogues. Biosci Rep. 1996;16:23-34 pubmed
    ..Hence, emiglitate might indirectly elicit an increased activity of the G(s)-proteins to facilitate the secretory process. ..
  46. Faridmoayer A, Scaman C. An improved purification procedure for soluble processing alpha-glucosidase I from Saccharomyces cerevisiae overexpressing CWH41. Protein Expr Purif. 2004;33:11-8 pubmed
    ..This suggests that the catalytic domain of yeast alpha-glucosidase I is resistant to trypsin hydrolysis and remains fully functional after cleavage. ..
  47. Shah N, Kuntz D, Rose D. Comparison of kifunensine and 1-deoxymannojirimycin binding to class I and II alpha-mannosidases demonstrates different saccharide distortions in inverting and retaining catalytic mechanisms. Biochemistry. 2003;42:13812-6 pubmed
    ..Thus, these two alpha-mannosidase classes distort these inhibitors in distinct manners. This is likely indicative of the binding characteristics of the two different catalytic mechanisms of these enzymes. ..
  48. Lachmann R. Miglustat: substrate reduction therapy for glycosphingolipid lysosomal storage disorders. Drugs Today (Barc). 2006;42:29-38 pubmed
    ..This article addresses both the preclinical and clinical development of miglustat for treatment of type 1 Gaucher's disease, as well as related neuronopathic glycosphingolipidoses. ..
  49. Markad S, Karanjule N, Sharma T, Sabharwal S, Dhavale D. Synthesis and evaluation of glycosidase inhibitory activity of N-butyl 1-deoxy-D-gluco-homonojirimycin and N-butyl 1-deoxy-L-ido-homonojirimycin. Bioorg Med Chem. 2006;14:5535-9 pubmed
  50. Schul W, Liu W, Xu H, Flamand M, Vasudevan S. A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J Infect Dis. 2007;195:665-74 pubmed
    ..The results validate this dengue viremia mouse model as a suitable system for testing antidengue drugs and indicate that antiviral treatment during the acute phase of dengue fever can reduce the severity of the disease. ..
  51. Arai M, Minatoguchi S, Kumada H, Uno Y, Nishida Y, Hashimoto K, et al. Role of protein kinase C in the reduction of infarct size by N-methyl-1-deoxynojirimycin, an alpha-1,6-glucosidase inhibitor. Br J Pharmacol. 2001;133:635-42 pubmed
    ..Thus, activation of PKC is a more direct mediator of the cardioprotection afforded by MOR-14 than is inhibition of glycogenolysis. ..
  52. Steiner A, Schitter G, Stütz A, Wrodnigg T, Tarling C, Withers S, et al. 1-Deoxygalactonojirimycin-lysine hybrids as potent D-galactosidase inhibitors. Bioorg Med Chem. 2008;16:10216-20 pubmed publisher
    ..Modifications on the lysine moiety by acylation gave access to lipophilic derivatives which exhibited excellent D-galactosidase inhibitory activities. ..
  53. Branza Nichita N, Durantel D, Carrouée Durantel S, Dwek R, Zitzmann N. Antiviral effect of N-butyldeoxynojirimycin against bovine viral diarrhea virus correlates with misfolding of E2 envelope proteins and impairment of their association into E1-E2 heterodimers. J Virol. 2001;75:3527-36 pubmed
    ..The degree of misfolding and the lack of association of E1 and E2 into disulfide-linked complexes in the presence of NB-DNJ correlate with the dose-dependent antiviral effect observed for this iminosugar. ..