A photocaged inhibitor of acid sphingomyelinase

Acid sphingomyelinase (ASM) is a potential drug target and involved in rapid lipid signalling events. However, there are no tools available to adequately study such processes. Based on a non cell-permeable PtdIns(3,5)P 2 inhibitor of ASM, we developed a compound with o -nitrobenzyl photocages and butyryl esters to transiently mask hydroxyl groups. This resulted in a potent light-inducible photocaged ASM inhibitor ( PCAI ). The first example of a time-resolved inhibition of ASM was shown in intact living cells. An esterase-labile, photocaged inhibitor provides spatiotemporal control over acid sphingomyelinase in living cells.