{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:07:47Z","timestamp":1789909667598,"version":"4.0.1"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100004329","name":"Genzyme","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["290836"],"award-info":[{"award-number":["290836"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["322942"],"award-info":[{"award-number":["322942"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M011151\/1"],"award-info":[{"award-number":["BB\/M011151\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gaucher disease is caused by inherited deficiency in glucocerebrosidase (GBA, a retaining \u03b2-glucosidase), and deficiency in GBA constitutes the largest known genetic risk factor for Parkinson\u2019s disease. In the past, animal models of Gaucher disease have been generated by treatment with the mechanism-based GBA inhibitors, conduritol B epoxide (CBE), and cyclophellitol. Both compounds, however, also target other retaining glycosidases, rendering generation and interpretation of such chemical knockout models complicated. Here we demonstrate that cyclophellitol derivatives carrying a bulky hydrophobic substituent at C8 are potent and selective GBA inhibitors and that an unambiguous Gaucher animal model can be readily generated by treatment of zebrafish with these.<\/jats:p>","DOI":"10.1021\/jacs.9b00056","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T13:39:21Z","timestamp":1551274761000},"page":"4214-4218","source":"Crossref","is-referenced-by-count":42,"title":["Functionalized\nCyclophellitols Are Selective Glucocerebrosidase\nInhibitors and Induce a Bona Fide Neuropathic Gaucher Model in Zebrafish"],"prefix":"10.1021","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-3902","authenticated-orcid":true,"given":"Marta","family":"Artola","sequence":"first","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-5008","authenticated-orcid":true,"given":"Chi-Lin","family":"Kuo","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey T.","family":"Lelieveld","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhianna J.","family":"Rowland","sequence":"additional","affiliation":[{"name":"University of York , , Heslington, ,","place":["York, United Kingdom, YO10 5DD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijsbert A.","family":"van der Marel","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-2138","authenticated-orcid":true,"given":"Jeroen D. C.","family":"Code\u0301e","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf G.","family":"Boot","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7343-776X","authenticated-orcid":true,"given":"Gideon J.","family":"Davies","sequence":"additional","affiliation":[{"name":"University of York , , Heslington, ,","place":["York, United Kingdom, YO10 5DD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M. F. G.","family":"Aerts","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-7005","authenticated-orcid":true,"given":"Herman S.","family":"Overkleeft","sequence":"additional","affiliation":[{"name":"Leiden University , , Einsteinweg 55 , ,","place":["Leiden, The Netherlands, 2333 CC"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"issue":"D1","key":"2026090305110812900_cit1","doi-asserted-by":"publisher","first-page":"D490","DOI":"10.1093\/nar\/gkt1178","article-title":"The Carbohydrate-Active\nEnzymes Database (CAZy) in 2013","volume":"42","author":"Lombard","year":"2014","journal-title":"Nucleic Acids\nRes."},{"key":"2026090305110812900_cit2","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1172\/JCI105417","article-title":"Demonstration of a\nDeficiency of Glucocerebroside-Cleaving Enzyme in Gaucher\u2019s\nDisease","volume":"45","author":"Brady","year":"1966","journal-title":"J. Clin. Invest."},{"key":"2026090305110812900_cit3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.mcn.2015.03.013","article-title":"Glucocerebrosidase\nand Parkinson Disease: Recent Advances","volume":"66","author":"Schapira","year":"2015","journal-title":"Mol.\nCell. Neurosci."},{"issue":"19","key":"2026090305110812900_cit4","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1212\/WNL.0b013e3182735e9a","article-title":"GBA Mutations Increase Risk for Lewy Body Disease with\nand without Alzheimer Disease Pathology","volume":"79","author":"Tsuang","year":"2012","journal-title":"Neurology"},{"issue":"17","key":"2026090305110812900_cit5","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter Analysis of Glucocerebrosidase\nMutations in Parkinson\u2019s Disease","volume":"361","author":"Sidransky","year":"2009","journal-title":"N.\nEngl. J. Med."},{"issue":"4","key":"2026090305110812900_cit6","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1172\/JCI117160","article-title":"Consequences\nof \u03b2-Glucocerebrosidase Deficiency in Epidermis. Ultrastructure\nand Permeability Barrier Alterations in Gaucher Disease","volume":"93","author":"Holleran","year":"1994","journal-title":"J. Clin. Invest."},{"key":"2026090305110812900_cit7","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1242\/dmm.008185","article-title":"Animal\nModels for Gaucher Disease\nResearch","volume":"4","author":"Farfel-Becker","year":"2011","journal-title":"Dis. Models & Mech."},{"key":"2026090305110812900_cit8","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/path.4751","article-title":"Delineating Pathological\nPathways in a Chemically Induced Mouse Model of Gaucher Disease","volume":"239","author":"Vardi","year":"2016","journal-title":"J. Pathol."},{"issue":"3","key":"2026090305110812900_cit9","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/febs.14744","article-title":"In Vivo Inactivation of Glycosidases by Conduritol B Epoxide and Cyclophellitol\nas Revealed by Activity-Based Protein Profiling","volume":"286","author":"Kuo","year":"2019","journal-title":"FEBS J."},{"key":"2026090305110812900_cit10","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1016\/S0021-9258(19)42174-1","article-title":"Affinity Labeling of the Active Sites\nin the Sucrase-Isomaltase Complex from Small Intestine","volume":"249","author":"Quaroni","year":"1974","journal-title":"J. Biol. Chem."},{"issue":"3","key":"2026090305110812900_cit11","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/0167-4838(85)90302-4","article-title":"Inactivation\nof \u03b1-Glucosidase by the Active-Site-Directed Inhibitor, Conduritol\nB Epoxide","volume":"828","author":"Shou-jun","year":"1985","journal-title":"Biochim. Biophys. Acta, Protein Struct.\nMol. Enzymol."},{"issue":"21","key":"2026090305110812900_cit12","doi-asserted-by":"crossref","first-page":"13507","DOI":"10.1016\/S0021-9258(18)92727-4","article-title":"Human\nLysosomal a-Glucosidase Characterization of the Catalytic Site","volume":"266","author":"Hermans","year":"1991","journal-title":"J. Biol. 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Acta, Mol.\nBasis Dis."},{"issue":"36","key":"2026090305110812900_cit15","doi-asserted-by":"publisher","first-page":"26052","DOI":"10.1074\/jbc.M113.463562","article-title":"\u03b2-Glucosidase\n2 (GBA2) Activity and Imino Sugar Pharmacology","volume":"288","author":"Ridley","year":"2013","journal-title":"J. Biol. Chem."},{"issue":"3","key":"2026090305110812900_cit16","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/0304-4165(79)90134-X","article-title":"Enzymic Effects\nof \u03b2-Glucosidase Destruction\nin Mice Changes in Glucuronidase Levels","volume":"582","author":"Hara","year":"1979","journal-title":"Biochim.\nBiophys. Acta, Gen. Subj."},{"issue":"12","key":"2026090305110812900_cit17","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/nchembio.466","article-title":"Ultrasensitive\nin Situ Visualization of Active Glucocerebrosidase Molecules","volume":"6","author":"Witte","year":"2010","journal-title":"Nat. Chem. 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Biol."},{"issue":"1","key":"2026090305110812900_cit22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/j.1365-2141.2010.08214.x","article-title":"Glucocerebrosidase\nDeficiency Dramatically Impairs Human Bone Marrow Haematopoiesis in\nan in Vitro Model of Gaucher Disease","volume":"150","author":"Berger","year":"2010","journal-title":"Br. J.\nHaematol."},{"issue":"1","key":"2026090305110812900_cit23","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1023\/B:BOLI.0000042959.44318.7c","article-title":"Correlation between\nEnzyme Activity and Substrate Storage\nin a Cell Culture Model System for Gaucher Disease","volume":"27","author":"Schueler","year":"2004","journal-title":"J. Inherited Metab. Dis."},{"key":"2026090305110812900_cit24","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/bs.mie.2017.06.039","article-title":"Activity-Based\nProbes for Glycosidases: Profiling and Other Applications","volume":"598","author":"Kuo","year":"2018","journal-title":"Methods Enzymol."},{"issue":"16","key":"2026090305110812900_cit25","doi-asserted-by":"publisher","first-page":"e118","DOI":"10.1182\/blood-2011-05-352971","article-title":"Elevated Plasma Glucosylsphingosine in Gaucher Disease:\nRelation to Phenotype, Storage Cell Markers, and Therapeutic Response","volume":"118","author":"Dekker","year":"2011","journal-title":"Blood"},{"key":"2026090305110812900_cit26","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1002\/1873-3468.12104","article-title":"Lysosomal\nGlycosphingolipid Catabolism by Acid Ceramidase: Formation of Glycosphingoid\nBases during Deficiency of Glycosidases","volume":"590","author":"Ferraz","year":"2016","journal-title":"FEBS\nLett."}],"container-title":["Journal of the American Chemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.9b00056","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/141\/10\/4214\/67193319\/jacs.9b00056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/141\/10\/4214\/67193319\/jacs.9b00056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:11:16Z","timestamp":1788426676000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/141\/10\/4214\/975923\/Functionalized-Cyclophellitols-Are-Selective"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,27]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,2,27]]},"published-print":{"date-parts":[[2019,3,13]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.9b00056","relation":{},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,27]]}}}