Eliglustat tartrate. Glucosylceramide synthase inhibitor treatment of type 1 gaucher disease

Drugs of the Future

Volumn 35, Issue 8, 2010, Pages 613-620

  Shayman, J A ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMFEBUTAMONE; AMIODARONE; CERAMIDE; CERAMIDE GLUCOSYLTRANSFERASE; CHLORPHENIRAMINE; CIMETIDINE; DEXAMETHASONE; DIPHENHYDRAMINE; ELIGLUSTAT; FLUOXETINE; GLUCOSYLCERAMIDE; GLYCOSPHINGOLIPID; HALOPERIDOL; HEMOGLOBIN; HYDROXYZINE; IMIGLUCERASE; METOCLOPRAMIDE; MIGLUSTAT; PAROXETINE; PHENOBARBITAL; RIFAMPICIN; SALBUTAMOL; SERTRALINE; THIORIDAZINE; URIDINE DIPHOSPHATE GLUCOSE;

ABDOMINAL PAIN; BREATHING RATE; DIARRHEA; DIZZINESS; DRUG EFFICACY; DRUG INTERACTION; DRUG SAFETY; DRUG TOLERABILITY; DYSGEUSIA; FABRY DISEASE; GASTROINTESTINAL DISEASE; GAUCHER DISEASE; GENOTOXICITY; HEADACHE; HEART PALPITATION; HEART RATE; HUMAN; IC 50; INTESTINE TRANSIT TIME; NEUROLOGICAL COMPLICATION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); POTASSIUM EXCRETION; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SPLEEN SIZE; STOMACH EMPTYING; THROAT IRRITATION; THROMBOCYTE COUNT; TREMOR; URINE PH; WEIGHT REDUCTION;

EID: 84952989751     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2010.035.08.1505566     Document Type: Review

References (40)

1. Dellaria, J.F. Jr., Santarsiero, B.D. Enantioselective synthesis of alpha-amino acid derivatives via the stereoselective alkylation of a homochiral glycine enolate synthon. J Org Chem 1989, 54(16): 3916-26.
2. Siegel, C., Hirth, B.H. (Genzyme Corp.). Synthesis of UDP-glucose:N-acylsphingosine glucosyltransferase inhibitors. CA 2453978, EP 1409467, EP 2067775, JP 2005255686, JP 2005502635, JP 2010095546, US 2003050299, US 6855830, WO 2003008399.
3. Charrow, J., Andersson, H.C., Kaplan, P. et al. The Gaucher registry: Demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 2000, 160(18): 2835-43.
4. Meikle, P. J., Hopwood, J.J., Clague, A.E., Carey, W.F. Prevalence of lysosomal storage disorders. JAMA 1999, 281(3): 249-54.
5. Grabowski, G.A. Gaucher disease: Gene frequencies and genotype/phenotype correlations. Genet Test 1997, 1(1): 5-12.
6. Kaplan, P., Andersson, H.C., Kacena, K.A., Yee, J.D. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med 2006, 160(6): 603-8.
7. Mignot, C., Doummar, D., Maire, I., De Villemeur, T.B. Type 2 Gaucher disease: 15 new cases and review of the literature. Brain Dev 2006, 28(1): 39-48.
8. Koprivica, V., Stone, D.L., Park, J.K. et al. Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet 2000, 66(6): 1777-86.
9. Weinreb, N.J., Aggio, M.C., Andersson, H.C. et al. Gaucher disease type 1: Revised recommendations on evaluations and monitoring for adult patients. Semin Hematol 2004, 41(4, Suppl. 5): 15-22.
10. Grabowski, G.A., Andria, G., Baldellou, A. et al. Pediatric non-neuronopathic Gaucher disease: Presentation, diagnosis and assessment. Consensus statements. Eur J Pediatr 2004, 163(2): 58-66.
11. Cox, T.M., Aerts, J.M., Belmatoug, N. et al. Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. J Inherit Metab Dis 2008, 31(3): 319-36.
12. Barton, N.W., Furbish, F.S., Murray, G.J., Garfield, M., Brady, R.O. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci U S A 1990, 87(5): 1913-6.
13. Barton, N.W., Brady, R.O., Dambrosia, J.M. et al. Replacement therapy for inherited enzyme deficiency - Macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med 1991, 324(21): 1464-70.
14. Ficicioglu, C. Review of miglustat for clinical management in Gaucher disease type 1. Ther Clin Risk Manag 2008, 4(2): 425-31.
15. Radin, N.S., Arora, R.C., Ullman, M.D., Brenkert, A.L., Austin, J. A possible therapeutic approach to Krabbe's globoid leukodystrophy and the status of cerebroside synthesis in the disorder. Res Commun Chem Pathol Pharmacol 1972, 3(3): 637-44.
16. Radin, N.S. Treatment of Gaucher disease with an enzyme inhibitor. Glycoconj J 1996, 13(2): 153-7.
17. Vunnam, R.R., Radin, N.S. Analogs of ceramide that inhibit glucocerebroside synthetase in mouse brain. Chem Phys Lipids 1980, 26(3): 265-78.
18. Shayman, J.A., Lee, L., Abe, A., Shu, L. Inhibitors of glucosylceramide synthase. Methods Enzymol 2000, 311: 373-87.
19. Abe, A., Inokuchi, J., Jimbo, M. et al. Improved inhibitors of glucosylceramide synthase. J Biochem 1992, 111(2): 191-6.
20. Abe, A., Radin, N.S., Shayman, J.A. et al. Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth. J Lipid Res 1995, 36(3): 611-21.
21. Lee, L., Abe, A., Shayman, J.A. Improved inhibitors of glucosylceramide synthase. J Biol Chem 1999, 274(21): 14662-9.
22. Abe, A., Arend, L.J., Lee, L., Lingwood, C., Brady, R.O., Shayman, J.A. Glycosphingolipid depletion in fabry disease lymphoblasts with potent inhibitors of glucosylceramide synthase. Kidney Int 2000, 57(2): 446-54.
23. Abe, A., Gregory, S., Lee, L., Killen, P.D., Brady, R.O., Kulkarni, A., Shayman, J.A. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest 2000, 105(11): 1563-71.
24. McEachern, K.A., Fung, J., Komarnitsky, S. et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab 2007, 91(3): 259-67.
25. Brumshtein, B., Greenblatt, H.M., Butters, T.D. 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(39): 29052-8.
26. Sanchez-Olle, G., Duque, J., Egido-Gabas, M. et al. Promising results of the chaperone effect caused by imino sugars and aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease. Blood Cells Mol Dis 2009, 42(2): 159-66.
27. Xu, Y.H., Quinn, B., Witte, D., Grabowski, G.A. Viable mouse models of acid beta-glucosidase deficiency: The defect in Gaucher disease. Am J Pathol 2003, 163(5): 2093-101.
28. Cheng, S.H., McEachern, K.M., Siegel, C. et al. Genz-112638, an oral ceramide analog for substrate inhibition therapy of Gaucher disease. J Inherit Metab Dis 2006, 29(Suppl. 1): 20.
29. Peterschmitt, M.J., Burke, A., Blanstein, L. et al. Safety, tolerability, and pharmacokinetics of eliglustat tartrate (Genz-112638) after single doses, multiple doses, and food in healthy volunteers. J Clin Pharmacol, In press.
30. Lukina, E., Watman, N., Arreguin, E.A. et al. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 2010, 116(6): 893-9.
31. Peterschmitt, J., Lukina, E., Watman, N. et al. Genz-112638, an investigational oral treatment for Gaucher disease type 1: Preliminary phase 2 clinical trial results. Mol Genet Metab 2009, 96(2): S34.
32. Weinreb, N.J., Barranger, J.A., Charrow, J., Grabowski, G.A., Mankin, H.J., Mistry, P. Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol 2005, 80(3): 223-9.
33. Zhou, S.F. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part II. Clin Pharmacokinet 2009, 48(12): 761-804.
34. Zhou, S.F. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet 2009, 48(11): 689-723.
35. Marshall, J., McEachern, K.A., Chuang, W.L. et al. Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy. J Inherit Metab Dis 2010, 33(3): 281-9.
36. Zhao, H., Przybylska, M., Wu, I.H. et al. Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes. Diabetes 2007, 56(5): 1210-8.
37. Zhao, H., Przybylska, M., Wu, I.H. et al. Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice. Hepatology 2009, 50(1): 85-93.
38. Radin, N.S. Killing cancer cells by poly-drug elevation of ceramide levels: A hypothesis whose time has come? Eur J Biochem 2001, 268(2): 193-204.
39. Hatch, S.C., Archer, J., Gummuluru, S. Glycosphingolipid composition of human immunodeficiency virus type 1 (HIV-1) particles is a crucial determinant for dendritic cell-mediated HIV-1 trans-infection. J Virol 2009, 83(8): 3496-506.
40. Natoli, T.A., Smith, L.A., Rogers, K.A. et al. Inhibition of glucosylceramide accumulation results in effective blockade of polycystic kidney disease in mouse models. Nat Med 2010, 16(7): 788-92.