Identification of Potent Caspase-8 Inhibitors from a Library of Fluorescent Natural Products Screened by an AIEgen-based Light-up Probe

摘要： Fluorescent natural products are a rich source of drugs and chemical probes. But their inborn fluorescence may interfere with the fluorescence-based screening assays. Caspase-8 is a key player in apoptosis. Inhibition of caspase-8 found to be beneficial for inflammatory and neurodegenerative diseases. But its small molecular inhibitors remain sparsely reported. In this study, we firstly developed a caspase-8 targeting light-up probe based on an AIEgen. This fluorescent dye has a Stokes shift of 200 nm which could avoid the inborn fluorescence signal of natural products. When screening a library of 86 fluorescent natural products, we found for the first time Gossypol showed potent inhibition towards caspase-8 in vitro and in situ. This unique kind of light-up probe coupled with colored natural products could be an efficient way in the hit discovery for druggable targets.