lucerastat (Idorsia)

Lucerastat (N-butyldeoxygalactonojirimycin, NB-DGJ) is an orally bioavailable, small-molecule iminosugar that acts as a substrate reduction therapy (SRT) for the treatment of glycolipid storage disorders, primarily Fabry disease. It functions by inhibiting ceramide glucosyltransferase (glucosylceramide synthase), the enzyme that catalyzes the first committed step of glycosphingolipid biosynthesis. By reducing the synthesis of glucosylceramide, lucerastat lowers the accumulation of downstream glycosphingolipids, such as globotriaosylceramide (Gb3), which build up in tissues and cause progressive organ damage in Fabry disease. Originally developed by Actelion and subsequently by its spin-off Idorsia, lucerastat has been evaluated in Phase 3 clinical trials (MODIFY and its open-label extension) for Fabry disease. Although it failed to meet its primary endpoint of reducing neuropathic pain, it demonstrated significant reductions in plasma and urinary Gb3 levels and showed potential renal benefits, leading to planned registrational trials focusing on kidney function.

Other names

1-butyl-2R-(hydroxymethyl)-3S,4R,5S-piperidinetriolN-Butyl-1-deoxygalactonojirimycinN-Butyl1-deoxygalactonojirimycinN-Butyl 1-deoxygalactonojirimycinN-Butyl-DGJN-butyldeoxygalactonojirimycinN-butyldeoxygalactonojirimycin (NB-DGJ)NB-DGJNBDGJlucerastatum