{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ullman JC"],"funding":["NIDDK NIH HHS","NINDS NIH HHS"],"pagination":["eadf1691"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10962247"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(730)"],"pubmed_abstract":["Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen. Chronic treatment with MZ-101 depleted muscle glycogen and was well tolerated in mice. Pompe disease, a glycogen storage disease caused by mutations in acid α glucosidase (GAA), results in pathological accumulation of glycogen and consequent autophagolysosomal abn"],"journal":["Science translational medicine"],"pubmed_title":["Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders."],"pmcid":["PMC10962247"],"funding_grant_id":["R35 NS116824","R01 DK027221"],"pubmed_authors":["DePaoli-Roach AA","Lee P","Morgans DJ","Ramanan V","Sarwaikar R","Beattie DT","Cummings BB","Green EM","Powers H","Hoek M","Noonberg SB","Blake K","Ganesh S","Won W","Hurley TD","Espanol B","Young LEA","O'Regan A","Bainer R","Fastman N","Dick RA","Merritt H","Sun RC","Santiago P","Xi Y","Choy R","Homburger JR","Wong P","Chandriani SJ","Tzitzilonis C","Roach PJ","Mellem KT","Satterfield TF","Lin B","Morton V","Gentry MS","Yu C","Ullman JC","Gujral T","Reiton D","Sinz C","Situ E","Graham RR","Tep S"],"additional_accession":[]},"is_claimable":false,"name":"Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.","description":"Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen. Chronic treatment with MZ-101 depleted muscle glycogen and was well tolerated in mice. Pompe disease, a glycogen storage disease caused by mutations in acid α glucosidase (GAA), results in pathological accumulation of glycogen and consequent autophagolysosomal abn","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2026-06-01T17:53:42.437Z","creation":"2025-04-06T01:15:10.978Z"},"accession":"S-EPMC10962247","cross_references":{"pubmed":["38232139"],"doi":["10.1126/scitranslmed.adf1691"]}}