Cyclodextrin-Based Iminosugar Click Clusters: The First Examples of Multivalent Pharmacological Chaperones for the Treatment of Lysosomal Storage Disorders

• Published in: Chembiochem : a European journal of chemical biology Vol. 13; no. 5; pp. 661 - 664
• Main Authors: Decroocq, Camille, Rodríguez-Lucena, David, Ikeda, Kyoko, Asano, Naoki, Compain, Philippe
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 19-03-2012; WILEY‐VCH Verlag
• Subjects: chaperones; Click Chemistry; cyclodextrins; Cyclodextrins - chemistry; Cyclodextrins - pharmacology; Cyclodextrins - therapeutic use; Gaucher's disease; Humans; Imino Sugars - chemistry; Imino Sugars - pharmacology; Imino Sugars - therapeutic use; iminosugars; Lysosomal Storage Diseases - drug therapy; Molecular Chaperones - chemistry; Molecular Chaperones - pharmacology; Molecular Chaperones - therapeutic use; Molecular Structure; multivalency
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201200005

Seven‐arm chaperone: A modest μM inhibitor of glucosylceramide β‐glucosidase (GCase) has been transformed into a potent low‐nM inhibitor by multivalency. This iminosugar inhibitor acts as a pharmacological chaperone and increases residual GCase activity in fibroblasts from Gaucher patients. These results open the way to a new class of chaperones for the treatment of lysosomal diseases.