生物活性

• 描述Miglustat (N-Butyldeoxynojirimycin) is an inhibitor of glucosylceramide synthase, primarily to treat Type I Gaucher disease (GD1)^[3]. Miglustat is an N-alkylated imino sugar that acts against a number of enzymes involved in processing glycoconjugates, including the ceramide-specific glucosyltransferase, which catalyzes the initial committed step in glycosphingolipid synthesis. Miglustat could therefore be used for substrate reduction therapy in glycosphingolipid lysosomal storage disorders^[4]. An immediate effect of Miglustat is its interference with carbohydrate digestion in the intestinal lumen via reversible inhibition of disaccharidases that cleave α-glycosidically linked carbohydrates. The inhibition of the disaccharidases function by Miglustat is mainly competitive and does not occur via alteration of the enzyme folding^[5]. Miglustat improves or stabilises several clinically relevant markers of NPC(Niemann-Pick type C disease) ^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02612129	Niemann-Pick Disease, Type C	Phase 2 Phase 3	Active, not recruiting	October 2020	United States, California ... more >> UCSF Benioff Children's Hospital Oakland Oakland, California, United States, 94609 United States, Minnesota Mayo Clinic Children's Center Rochester, Minnesota, United States, 55905 Denmark University Hospital Copenhagen (Rigshospitalet) Copenhagen, Denmark, 2100 France CHU de Montpellier Montpellier, France, 34295 Montpellier Cedex 5 Hôpital Trousseau Paris, France, 75571 PARIS Cedex 12 Germany Villa Metabolica Mainz Mainz, Germany, 55131 Dr. von Haunersches Kinderspital der Universität München Munich, Germany, 80337 Italy Ospedale Pediatrico Bambino Gesù Rome, Italy, 00165 Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" di Udin Udine, Italy, 33100 Poland The Children´s Memorial Istitute Warsaw Warsaw, Poland, 04-730 Spain Hospital Vall D'Hebron Barcelona, Spain, 08035 Switzerland INSELSPITAL University Hospital Bern Bern, Switzerland, CH-3010 United Kingdom Birmingham Children's Hospital Birmingham, United Kingdom, B4 6NH Great Ormond Street Hospital London, United Kingdom, WC1N 3JH Collapse <<
  NCT00000791	HIV Infections	Phase 2	Completed	-	United States, Alabama ... more >> Alabama Therapeutics CRS Birmingham, Alabama, United States United States, California USC CRS Los Angeles, California, United States, 90033 Stanford CRS Palo Alto, California, United States Ucsf Aids Crs San Francisco, California, United States, 94110 United States, Colorado University of Colorado Hospital CRS Aurora, Colorado, United States United States, Florida Univ. of Miami AIDS CRS Miami, Florida, United States United States, Illinois Northwestern University CRS Chicago, Illinois, United States, 60611 Rush Univ. Med. Ctr. ACTG CRS Chicago, Illinois, United States, 60612 Weiss Memorial Hosp. Chicago, Illinois, United States, 60640 Cook County Hosp. CORE Ctr. Chicago, Illinois, United States United States, Indiana Indiana Univ. School of Medicine, Infectious Disease Research Clinic Indianapolis, Indiana, United States Methodist Hosp. of Indiana Indianapolis, Indiana, United States United States, Missouri St. Louis ConnectCare, Infectious Diseases Clinic St. Louis, Missouri, United States, 63112 Washington U CRS St. Louis, Missouri, United States United States, New York SUNY - Buffalo, Erie County Medical Ctr. Buffalo, New York, United States, 14260 Beth Israel Med. Ctr. (Mt. Sinai) New York, New York, United States Univ. of Rochester ACTG CRS Rochester, New York, United States United States, North Carolina Unc Aids Crs Chapel Hill, North Carolina, United States, 27514 Wake County Health and Human Services CRS Raleigh, North Carolina, United States United States, Ohio Univ. of Cincinnati CRS Cincinnati, Ohio, United States United States, Pennsylvania Hosp. of the Univ. of Pennsylvania CRS Philadelphia, Pennsylvania, United States United States, Washington University of Washington AIDS CRS Seattle, Washington, United States, 98104 Collapse <<
  NCT02675465	Pompe Disease	Phase 1 Phase 2	Recruiting	September 2019	United States, Arizona ... more >> Neuromuscular Research Centre Recruiting Phoenix, Arizona, United States, 85028 Contact: Kumaraswamy Sivakumar    480-314-1007 ext 6    ksiva@nrcaz.com    Contact: Kristy Osgood    480-314-1007 ext 6    kosgood@nrcaz.com    Principal Investigator: Kumaraswamy Sivakumar          United States, California University of California Irvine Recruiting Orange, California, United States, 92868 Contact: Tahseen Mozaffar    714-456-2332    Mozaffar@uci.edu    Contact: Marie Wencel    714-456-2525    mwencel@uci.edu    Principal Investigator: Tahseen Mozaffar          United States, Florida University of Florida Recruiting Gainesville, Florida, United States, 32610 Contact: Barry J Byrne    352-273-6563    bbyrne@ufl.edu    Contact: Lee Kugelmann    352-273-6588    ekugelm@ufl.edu    Principal Investigator: Barry Byrne          United States, Georgia Emory University Division of Medical Genetics Completed Decatur, Georgia, United States, 30033 United States, Michigan Infusion Associates Recruiting Grand Rapids, Michigan, United States, 49525 Contact: Khan Nedd, MD    616-954-0600    khan.nedd@infusionassociates.com    Contact: Katie May    616-818-4473    katie.may@infusionassociates.com    Principal Investigator: Khan Nedd          United States, Montana Great Falls Clinic, LLP Recruiting Great Falls, Montana, United States, 59405 Contact: Karl Guter    406-771-3311    karl.guter@gfclinic.com    Contact: Jacob Decker    406-771-3373    jacob.decker@gfclinic.com    Principal Investigator: Karl Guter          United States, New Jersey Rutgers New Jersey Medical School Recruiting Newark, New Jersey, United States, 08103 Contact: Xue Ming    973-972-2922    mingxu@njms.rutgers.edu    Contact: Eliana Obando-Jaramillo    973-972-5435    emo65@njms.rutgers.edu    Principal Investigator: Xue Ming          United States, North Carolina Duke University Medical Center Recruiting Durham, North Carolina, United States, 27710 Contact: Priya Kishnani    919-684-2036    priya.kishnani@dm.duke.edu    Contact: Ela Stefanescu    919-681-4026    mihaela.stefanescu@duke.edu    Principal Investigator: Priya Kishnani          United States, Pennsylvania University of Pittsburgh Recruiting Pittsburgh, Pennsylvania, United States, 15213 Contact: Paula Clemens    412-648-9762    clempr@upmc.edu    Contact: Gabriela A Niizawa    412-383-9775    niizawaga@upmc.edu    Principal Investigator: Paula Clemens          United States, Virginia Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) Recruiting Fairfax, Virginia, United States, 22030 Contact: Ozlem Goker-Alpan, MD    571-308-1925    ogoker-alpan@ldrtc.org    Contact: Jacqueline Fikry    703-261-6220 ext 105    jfikry@ldrtc.org    Principal Investigator: Ozlem Goker-Alpan          Australia, South Australia Womens & Childrens Hospital, Adelaide Active, not recruiting North Adelaide, South Australia, Australia, 05006 Germany University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital Recruiting Bochum, Germany, 44791 Contact: Peter Schwenkreis    +49 (0) 176 55 12 95 38    peter.schwenkreis@bergmannsheil.de    Contact: Rebecca Trost    +49 234 3023139    rebecca.trost@bergmannsheil.de    Principal Investigator: Schwenkreis Peter          Friedrich-Baur-Institure, Dep of Neurology - University Munich Recruiting Munich, Germany, 80336 Contact: Benedikt Schoser    +49 (0) 89 4400 57400    benedikt.schoser@med.uni-muenchen.de    Contact: Stephan Wenninger    +49 (0) 89 4400 57470    Stephan.Wenninger@med.uni-muenchen.de    Principal Investigator: Benedikt Schoser          Netherlands Erasmus Medical Center Recruiting Rotterdam, Netherlands Contact: A.T. van der Ploeg    31107037254    a.vanderploeg@erasmusmc.nl    Contact: Jacqueline Hardon    31107037047    j.hardon@erasmusmc.nl    Principal Investigator: A.T. van der Ploeg          United Kingdom University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center Completed Birmingham, United Kingdom, B15 2TH Salford Royal NHS Foundation Trust Recruiting Salford, United Kingdom, M6 8HD Contact: Mark Roberts    0161-206-4365    mark.roberts@srft.nhs.uk    Contact: Catherine Wilson    44- 01612064851    Catherine.Wilson@srft.nhs.uk    Principal Investigator: Mark Roberts Collapse <<

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• 参考文献

• [1] Abian O, Alfonso P, et al. Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase. Mol Pharm. 2011 Dec 5;8(6):2390-7.

  [2] 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.

  [3] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Miglustat. 2018 Mar 5

  [4] Lachmann RH. Miglustat: substrate reduction therapy for glycosphingolipid lysosomal storage disorders. Drugs Today (Barc). 2006 Jan;42(1):29-38

  [5] Amiri M, Naim HY. Miglustat-induced intestinal carbohydrate malabsorption is due to the inhibition of α-glucosidases, but not β-galactosidases. J Inherit Metab Dis. 2012 Nov;35(6):949-54

  [6] 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

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