OSMI-2 is a cell-permeable precursor of an active site-targeting (Kd = 140 nM) O-GlcNAc transferase (OGT) inhibitor. Upon cell entry, OSMI-2 is activated by cellular esterase to the active inhibitor th at effectively downregulates cellular protein O-GlcNAc level (20-40 μM for 4 h/HCT116, 50 μM for 24 h/HEK293T) and renders LNCaP prostate cancer cells dependent on CDK9 for growth (confluency post 96-hr treatment = 73% with 40 μM OSMI-2, 56% with 0.5 μM AT7519, 19% with co-treatment; control cells at 20% and 81% at 0 and 96 hr, respectively).
