{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:10Z","timestamp":1786977550313,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glycosphingolipid (GSL) storage diseases are caused by deficiencies in the enzymes that metabolize different GSLs in the lysosome. Glucosylceramide synthase (GCS) inhibitors reduce GSL production and have potential to treat multiple GSL storage diseases. AL01211 is a potent, oral GCS inhibitor being developed for the treatment of Type 1 Gaucher disease and Fabry disease. AL01211 has minimal central nervous system penetration, allowing for treatment of peripheral organs without risking CNS\u2010associated adverse effects. AL01211 was evaluated in a Phase 1 healthy volunteer study with single ascending dose (SAD) and multiple ascending dose (MAD) arms, to determine safety, pharmacokinetics including food effect, and pharmacodynamic effects on associated GSLs. In the SAD arm, AL01211 showed a Tmax\u00a0of approximately 3.5 hours, mean clearance (CL\/F) of 130.1 L\/h, and t\n                    <jats:sub>1\/2<\/jats:sub>\n                    \u00a0of 39.3 hours. Consuming a high\u2010fat meal prior to dose administration reduced exposures 3.5\u20105.5\u2010fold, indicating a food effect. In the MAD arm, AL01211 had an approximately 2\u2010fold accumulation, reaching steady\u2010state levels by 10 days. Increasing exposure inversely correlated with a decrease in GSL with plasma glucosylceramide and globotriacylceramide reduction from baseline levels, reaching 78% and 52% by day 14, respectively. AL01211 was generally well\u2010tolerated with no AL01211 associated serious adverse events, thus supporting its further clinical development.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1375","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T07:04:47Z","timestamp":1708067087000},"page":"696-709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Phase 1 Healthy Volunteer Study of AL01211, an Oral, Non\u2010brain Penetrant Glucosylceramide Synthase Inhibitor, to Treat Fabry Disease and Type 1 Gaucher Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Michael","family":"Babcock","sequence":"first","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gail Shurr","sequence":"additional","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical San Rafael CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Huertas","sequence":"additional","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip John","family":"Ryan","sequence":"additional","affiliation":[{"name":"Nucleus Network  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiao","family":"Shen","sequence":"additional","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Garovoy","sequence":"additional","affiliation":[{"name":"AceLink Therapeutics Newark CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2018.01.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R047167"},{"key":"e_1_2_9_4_1","volume-title":"Essentials of Glycobiology","author":"Schnaar RL","year":"2022"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-013118-111518"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R003996"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18020441"},{"key":"e_1_2_9_8_1","volume-title":"StatPearls","author":"Stone WL","year":"2023"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62702-5.00017-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-6-200703200-00007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16020320"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175023"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15402"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1025740"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010206"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.00653.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031887"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104178"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-758409"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4103\/jrpp.JRPP_18_24"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.865"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.11.002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2022.10.016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac379"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00205-3"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.944"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.790"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","unstructured":"BabcockM.Development of AL01211 a Novel Glucosylceramide Synthase Inhibitor to Treat Autosomal Dominant Polycystic Kidney Disease (ADPKD). Poster PO1198 presented at the:American Society of Nephrology Kidney Week;2021.","DOI":"10.1681\/ASN.20213210S1391a"},{"issue":"8","key":"e_1_2_9_29_1","first-page":"44","article-title":"7th Update on fabry disease: biomarkers, progression and treatment opportunities in 2022","volume":"146","author":"Warnock DG","year":"2022","journal-title":"Nephron"},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","unstructured":"BabcockM.Development of AL01211 an oral non\u2010brain penetrant glucosylceramide synthase inhibitor (GCSi) to treat Fabry disease. 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