{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:29:05Z","timestamp":1791224945167,"version":"4.1.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2007,7,1]],"date-time":"2007-07-01T00:00:00Z","timestamp":1183248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Genetics and Metabolism"],"published-print":{"date-parts":[[2007,7]]},"DOI":"10.1016\/j.ymgme.2007.04.001","type":"journal-article","created":{"date-parts":[[2007,5,17]],"date-time":"2007-05-17T17:49:10Z","timestamp":1179424150000},"page":"259-267","source":"Crossref","is-referenced-by-count":152,"title":["A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease"],"prefix":"10.1016","volume":"91","author":[{"given":"Kerry Anne","family":"McEachern","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Komarnitsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Siegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Lien","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Hutto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Shayman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Grabowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.F.G.","family":"Aerts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng H.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane P.","family":"Copeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymgme.2007.04.001_bib1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1365-2141.2004.05293.x","article-title":"Lysosomal storage disorders","volume":"128","author":"Vellodi","year":"2004","journal-title":"British J. Hematology"},{"key":"10.1016\/j.ymgme.2007.04.001_bib2","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/j.bbamem.2006.05.027","article-title":"Sphingolipid metabolism diseases","volume":"1758","author":"Kolter","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymgme.2007.04.001_bib3","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s00018-002-8458-y","article-title":"Gaucher disease: perspectives on a prototype lysosomal disease","volume":"59","author":"Zhao","year":"2002","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.ymgme.2007.04.001_bib4","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0002-9343(02)01150-6","article-title":"Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2\u20135 years of treatment: A report from the Gaucher Registry","volume":"113","author":"Weinreb","year":"2002","journal-title":"Am. J. Med."},{"key":"10.1016\/j.ymgme.2007.04.001_bib5","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1517\/13543776.13.8.1157","article-title":"Enzyme therapy for the lysosomal storage disorders: principles, patents, practice and prospects","volume":"13","author":"Pastores","year":"2003","journal-title":"Expert Opin. Ther. Patents"},{"key":"10.1016\/j.ymgme.2007.04.001_bib6","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s10545-006-0239-6","article-title":"Limitations of enzyme replacement therapy: current and future","volume":"29","author":"Wraith","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"issue":"Suppl. 2","key":"10.1016\/j.ymgme.2007.04.001_bib7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1023\/A:1012452715079","article-title":"Remaining problems in the management of patients with Gaucher disease","volume":"24","author":"Erikson","year":"2001","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2007.04.001_bib8","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2165\/00003495-200262050-00002","article-title":"New prospects for the treatment of lysosomal storage diseases","volume":"62","author":"Schiffman","year":"2002","journal-title":"Drugs"},{"key":"10.1016\/j.ymgme.2007.04.001_bib9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF00731489","article-title":"Treatment of Gaucher disease with an enzyme inhibitor","volume":"13","author":"Radin","year":"1996","journal-title":"Glyconj. J."},{"key":"10.1016\/j.ymgme.2007.04.001_bib10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1517\/13543784.10.3.455","article-title":"Substrate reduction therapy for glycosphingolipid storage disorders","volume":"10","author":"Lachmann","year":"2001","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.ymgme.2007.04.001_bib11","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1098\/rstb.2003.1273","article-title":"Biochemistry of glycosphingolipid storage disorders: implications for therapeutic intervention","volume":"358","author":"Aerts","year":"2003","journal-title":"Phil. Trans. R. Soc. Lond. B"},{"key":"10.1016\/j.ymgme.2007.04.001_bib12","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10545-006-0272-5","article-title":"Substrate reduction therapy of glycosphingolipid storage disorders","volume":"29","author":"Aerts","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2007.04.001_bib13","first-page":"472","article-title":"Miglustat Oxford Glycosciences\/Actelion","volume":"4","author":"Lachmann","year":"2003","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"10.1016\/j.ymgme.2007.04.001_bib14","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0140-6736(00)02161-9","article-title":"Novel oral treatment of Gaucher\u2019s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis","volume":"355","author":"Cox","year":"2000","journal-title":"Lancet"},{"key":"10.1016\/j.ymgme.2007.04.001_bib15","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/bcmd.2002.0497","article-title":"Low-dose N-butyldeoxynojirimycin (OCT 918) for type 1 Gaucher disease","volume":"28","author":"Heitner","year":"2002","journal-title":"Blood Cells, Molec. Dis."},{"key":"10.1016\/j.ymgme.2007.04.001_bib16","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.clinthera.2005.08.004","article-title":"An open-label, non-comparative study of Miglustat in type 1 Gaucher disease: Efficacy and tolerability over 24 months of treatment","volume":"27","author":"Pastore","year":"2005","journal-title":"Clin. Therapeutics"},{"key":"10.1016\/j.ymgme.2007.04.001_bib17","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0022-2275(20)39895-3","article-title":"Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth","volume":"36","author":"Abe","year":"1995","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.ymgme.2007.04.001_bib18","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/BF00731481","article-title":"Studies of the action of ceramide-like substances (d- and l-PDMP) on sphingolipid glycosyltransferases and purified lactosylceramide synthase","volume":"13","author":"Chatterjee","year":"1996","journal-title":"Glycoconj. J."},{"key":"10.1016\/j.ymgme.2007.04.001_bib19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/oxfordjournals.jbchem.a123736","article-title":"Improved inhibitors of glucosylceramide synthase","volume":"111","author":"Abe","year":"1992","journal-title":"J. Biochem."},{"key":"10.1016\/j.ymgme.2007.04.001_bib20","doi-asserted-by":"crossref","first-page":"14662","DOI":"10.1074\/jbc.274.21.14662","article-title":"Improved inhibitors of glucosylceramide synthase","volume":"274","author":"Lee","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2007.04.001_bib21","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1046\/j.1523-1755.2000.00864.x","article-title":"Glycosphingolipid depletion in Fabry disease lymphoblasts with potent inhibitors of glucosylceramide synthase","volume":"57","author":"Abe","year":"2000","journal-title":"Kidney Int."},{"key":"10.1016\/j.ymgme.2007.04.001_bib22","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1172\/JCI9711","article-title":"Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation","volume":"105","author":"Abe","year":"2000","journal-title":"J. Clin. Inv."},{"key":"10.1016\/j.ymgme.2007.04.001_bib23","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1750-3639.1998.tb00145.x","article-title":"Mouse models of human lysosomal diseases","volume":"8","author":"Suzuki","year":"1998","journal-title":"Brain Pathol."},{"key":"10.1016\/j.ymgme.2007.04.001_bib24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1098\/rstb.2003.1279","article-title":"Substrate reduction therapy in mouse models of the glycosphingolipidoses","volume":"358","author":"Platt","year":"2003","journal-title":"Phil. Trans. R. Soc. Lond. B"},{"key":"10.1016\/j.ymgme.2007.04.001_bib25","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1016\/S0002-9440(10)63566-3","article-title":"Viable mouse models of acid \u03b2-glucosidase deficiency","volume":"163","author":"Xu","year":"2003","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.ymgme.2007.04.001_bib26","unstructured":"B.H. Hirth, C. Siegel, Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors. U.S. Patent #6,855,830 (2005)."},{"key":"10.1016\/j.ymgme.2007.04.001_bib27","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0006-2952(99)00384-6","article-title":"N-butyldeoxygalactonojirimycin: a more selective inhibitor of glycosphingolipid biosynthesis than N-butyldeoxynojirimycin, in vitro and in vivo","volume":"59","author":"Andersson","year":"2000","journal-title":"Biochem. Pharm."},{"key":"10.1016\/j.ymgme.2007.04.001_bib28","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.bcp.2003.09.036","article-title":"Inhibition of glycogen breakdown by imino sugars in vitro and in vivo","volume":"67","author":"Andersson","year":"2004","journal-title":"Biochem. Pharm."},{"key":"10.1016\/j.ymgme.2007.04.001_bib29","doi-asserted-by":"crossref","first-page":"26522","DOI":"10.1074\/jbc.273.41.26522","article-title":"Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase","volume":"273","author":"Overkleeft","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2007.04.001_bib30","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.2337\/db06-0719","article-title":"Inhibiting glycospingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes","volume":"56","author":"Zhao","year":"2007","journal-title":"Diabetes"},{"key":"10.1016\/j.ymgme.2007.04.001_bib31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0022-2143(96)90183-3","article-title":"Analysis of the lipids of normal and Gaucher bone marrow","volume":"127","author":"Miller","year":"1996","journal-title":"J. Lab. Clin. Med."},{"key":"10.1016\/j.ymgme.2007.04.001_bib32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0076-6879(66)08014-5","article-title":"Assay of inorganic phosphate, total phosphate and phosphatase","volume":"8","author":"Ames","year":"1966","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.ymgme.2007.04.001_bib33","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/jgm.901","article-title":"AAV8-mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease","volume":"8","author":"McEachern","year":"2006","journal-title":"J. Gene Med."},{"key":"10.1016\/j.ymgme.2007.04.001_bib34","doi-asserted-by":"crossref","first-page":"11038","DOI":"10.1074\/jbc.274.16.11038","article-title":"Sphingolipid activator proteins are required for epidermal permeability barrier formation","volume":"274","author":"Doering","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2007.04.001_bib35","doi-asserted-by":"crossref","first-page":"19365","DOI":"10.1074\/jbc.272.31.19365","article-title":"Extensive glycospingolipid depletion in the liver and lymphoid organs of mice treated with N-butyldeoxynojirimycin","volume":"272","author":"Platt","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymgme.2007.04.001_bib36","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1056\/NEJM199105233242104","article-title":"Replacement therapy for inherited enzyme deficiency \u2013 macrophage-targeted glucocerebrosidase for Gaucher\u2019s disease","volume":"324","author":"Barton","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymgme.2007.04.001_bib37","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jpeds.2004.01.050","article-title":"Gaucher disease: Lessons from a decade of therapy","volume":"144","author":"Grabowski","year":"2004","journal-title":"J. Pediatr."},{"key":"10.1016\/j.ymgme.2007.04.001_bib38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1182\/blood.V90.1.43","article-title":"Enzyme therapy in Gaucher disease Type 1: effect of neutralizing antibodies to acid beta-glucosidase","volume":"90","author":"Ponce","year":"1997","journal-title":"Blood"},{"key":"10.1016\/j.ymgme.2007.04.001_bib39","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s00431-001-0859-7","article-title":"Glucocerebrosidase level in the cerebrospinal fluid during enzyme replacement therapy\u2014unsuccessful treatment of the neurological abnormality in type 2 Gaucher disease","volume":"162","author":"Migita","year":"2003","journal-title":"Eur. J. Pediatr."},{"key":"10.1016\/j.ymgme.2007.04.001_bib40","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S0140-6736(87)91673-4","article-title":"Beneficial effects of pretransplant splenectomy on displacement bone marrow transplantation for Gaucher\u2019s disease","volume":"329","author":"Hobbs","year":"1987","journal-title":"Lancet"},{"key":"10.1016\/j.ymgme.2007.04.001_bib41","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1097\/00007890-199503000-00011","article-title":"Ten years experience of bone marrow transplantation for Gaucher disease","volume":"59","author":"Ringden","year":"1995","journal-title":"Transplantation"},{"key":"10.1016\/j.ymgme.2007.04.001_bib42","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1023\/B:BOLI.0000045756.54006.17","article-title":"Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type 1 Gaucher disease","volume":"27","author":"Elstein","year":"2004","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.ymgme.2007.04.001_bib43","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1182\/blood.V86.3.1218.1218","article-title":"Transfer of the human glucocerebrosidase gene into hematopoietic stem cells of nonablated recipients: Successful engraftment and long-term expression of the transgene","volume":"86","author":"Schiffmann","year":"1995","journal-title":"Blood"}],"container-title":["Molecular Genetics and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719207001254?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096719207001254?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T21:54:27Z","timestamp":1628891667000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096719207001254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,7]]}},"alternative-id":["S1096719207001254"],"URL":"https:\/\/doi.org\/10.1016\/j.ymgme.2007.04.001","relation":{},"ISSN":["1096-7192"],"issn-type":[{"value":"1096-7192","type":"print"}],"subject":[],"published":{"date-parts":[[2007,7]]}}}