Hit identification and hit-to-lead optimization are key steps of the early drug discovery program. Starting from the X-ray crystal structure of the human monoacylglycerol lipase (hMAGL), we herein describe the computational and experimental procedures that we applied for identifying and optimizing a new active inhibitor of this target enzyme. A receptor-based virtual screening method is reported in details, together with enzymatic assays and a first round of hit optimization.
Keywords: Hit identification; Hit-to-lead optimization; MAGL; Monoacylglycerol lipase inhibitors; Virtual screening.