IMP-2352

IMP-2352 is a potent and selective activity-based probe (ABP) and inhibitor of Kallikrein-related peptidase 6 (KLK6), a serine protease implicated in the progression and metastasis of pancreatic ductal adenocarcinoma (PDAC). Developed using a positional scanning combinatorial substrate library, IMP-2352 exhibits high potency (kobs/I = 11,000 M-1 s-1) and enables the selective detection of KLK6 activity in various PDAC cell lines. By covalently binding to the active site of KLK6, it inhibits the enzyme's ability to cleave extracellular matrix proteins and initiate signaling cascades, thereby reducing the invasiveness of cancer cells. This molecule serves as a critical chemical biology tool for validating KLK6 as a therapeutic target and for identifying its secreted protein substrates.