Sinbaglustat (OGT2378) is a dual inhibitor of glucosylceramide synthase (GCS) and non-lysosomal glucosyl ceramidase (GBA2). Sinbaglustat is an orally available N-alkyl iminosugar that crosses the blood-brain barrier. Sinbaglustat can be used for the research of central neurodegenerative diseases associated with lysosomal dysfunctions[2].In Vitro: Sinbaglustat (OGT2378; 20 μM) reduces the synthesis of glucosylceramide and ganglioside by 93% and >95% in MEB4 melanoma cells compared with untreated MEB4 cells, respectively, without either cytotoxic or antiproliferative effects.
GBA2 is an enzyme involved in the catabolism of glycosphingolipids (GSLs).?Sinbaglustat is 50-fold more potent in inhibiting GBA2 than GCS[2].In Vivo: Sinbaglustat (OGT2378; administered p.o., in the powdered chow, at a dose of 2500 mg/kg/day, corresponding to 35-40 mg of Sinbaglustat per mouse per day) is highly effective in impeding melanoma tumor growth?in vivo. The effectiveness of p.o. Sinbaglustat in this murine model suggests that inhibition of glycosphingolipid synthesis is a promising approach to inhibit tumor progression.