NCGC-607

NCGC-607 is a small-molecule, noninhibitory pharmacological chaperone of the lysosomal enzyme glucocerebrosidase (GCase), developed by the National Human Genome Research Institute (NHGRI). Unlike traditional inhibitory chaperones that bind to the enzyme's active site, NCGC-607 acts as an allosteric modulator, binding to specific sites on the GCase surface to stabilize the protein and enhance its translocation to the lysosome. This stabilization increases GCase activity and protein levels. NCGC-607 is primarily being investigated for the treatment of Gaucher disease (GD) and Parkinson's disease (PD), particularly in patients with GBA1 gene mutations. Preclinical studies in patient-derived cell cultures, including iPSC-derived dopaminergic neurons and macrophages, have demonstrated its ability to restore enzyme function, reduce the accumulation of glycolipid substrates (glucosylceramide and glucosylsphingosine), and decrease levels of alpha-synuclein.

Other names

NCGC00241607NCGC-00241607NCGC 00241607