Novel glucocerebrosidase (GC) Probes. A) The fluorescence GC enzyme assay developed using the pro-fluorescent substrate 4-methylumbelliferone-β-D-glucopyranoside as a substrate for the GC enzyme. B) The entire qHTS data set. Samples where the CRCs could be fit to the data are shown in light blue (high-quality CRCs) or dark blue (CRCs showing fits of lower confidence), while data that did not show any CRC is shown in orange. C) The chemical structure of NCGC00092410 (1) D) the selectivity profile from 1 versus GC, α-glucosidase, α-galactosidase or β-N-acetylflucosaminidase. E) Overlay image from the dual labeling [(GC Ab, red) and (Lysotracker, green)] of cells expressing the clinically relevant N370S GC mutant in the presence of 40 μM of NCGC00092410. Colocalization of N370S GC to the lysosome presents as yellow.