{"entity": "publication", "iuid": "c91ecd53381846a3aa62a6b266b7b410", "timestamp": "2026-08-22T07:48:22.628Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c91ecd53381846a3aa62a6b266b7b410.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c91ecd53381846a3aa62a6b266b7b410"}}, "title": "Inhibitors of dermatan sulfate epimerase 1 decreased accumulation of glycosaminoglycans in mucopolysaccharidosis type I fibroblasts.", "authors": [{"family": "Maccarana", "given": "Marco", "initials": "M", "orcid": "0000-0003-3549-8921", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca8e408602c742478ab42e041504eb38.json"}}, {"family": "Li", "given": "Binjie", "initials": "B", "orcid": "0000-0003-4058-180X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b9474621a26f49558f430c91d61fce07.json"}}, {"family": "Li", "given": "Honglian", "initials": "H", "orcid": "0000-0002-5820-3121", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7a3ac57ba039433b8eacad4504af66fd.json"}}, {"family": "Fang", "given": "Jianping", "initials": "J", "orcid": "0000-0002-1695-2693", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19a0d0b14f1f4fd7afbc007555207b5c.json"}}, {"family": "Yu", "given": "Mingjia", "initials": "M", "orcid": "0000-0002-8906-7476", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e7da2d9779f41e68ad8e99ab4874812.json"}}, {"family": "Li", "given": "Jin-Ping", "initials": "JP", "orcid": "0000-0002-4255-3581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ab4d6e3d5eb4551a1cc622b5917dc3b.json"}}], "type": "journal article", "published": "2024-04-24", "journal": {"title": "Glycobiology", "issn": "1460-2423", "volume": "34", "issue": "6", "issn-l": "0959-6658"}, "abstract": "Genetic deficiency of alpha-L-iduronidase causes mucopolysaccharidosis type I (MPS-I) disease, due to accumulation of glycosaminoglycans (GAGs) including chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) in cells. Currently, patients are treated by infusion of recombinant iduronidase or by hematopoietic stem cell transplantation. An alternative approach is to reduce the L-iduronidase substrate, through limiting the biosynthesis of iduronic acid. Our earlier study demonstrated that ebselen attenuated GAGs accumulation in MPS-I cells, through inhibiting iduronic acid producing enzymes. However, ebselen has multiple pharmacological effects, which prevents its application for MPS-I. Thus, we continued the study by looking for novel inhibitors of dermatan sulfate epimerase 1 (DS-epi1), the main responsible enzyme for production of iduronic acid in CS/DS chains. Based on virtual screening of chemicals towards chondroitinase AC, we constructed a library with 1,064 compounds that were tested for DS-epi1 inhibition. Seventeen compounds were identified to be able to inhibit 27%-86% of DS-epi1 activity at 10 \u03bcM. Two compounds were selected for further investigation based on the structure properties. The results show that both inhibitors had a comparable level in inhibition of DS-epi1while they had negligible effect on HS epimerase. The two inhibitors were able to reduce iduronic acid biosynthesis in CS/DS and GAG accumulation in WT and MPS-I fibroblasts. Docking of the inhibitors into DS-epi1 structure shows high affinity binding of both compounds to the active site. The collected data indicate that these hit compounds may be further elaborated to a potential lead drug used for attenuation of GAGs accumulation in MPS-I patients.", "doi": "10.1093/glycob/cwae025", "pmid": "38760939", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11101759"}, {"db": "pii", "key": "7676076"}], "notes": [], "created": "2026-08-21T12:08:53.529Z", "modified": "2026-08-21T12:08:53.804Z"}