Human acidic mammalian chitinase as a novel target for anti-asthma drug design using in silico screening

Abstract Human acidic mammalian chitinase ( h AMCase) was recently shown to be involved in the development of asthma, suggesting a possible application for h AMCase inhibitors as novel therapeutic agents for asthma. We therefore initiated drug discovery research into h AMCase using a combination of in silico methodologies and a h AMCase assay system. We first selected 23 candidate h AMCase inhibitors from a database of four million compounds using a multistep screening system combining Tripos Topomer Search technology, a docking calculation and two-dimensional molecular similarity analysis. We then measured h AMCase inhibitory activity of the selected compounds and identified seven compounds with IC 50 values ⩽100 μM. A model describing the binding modes of these hit compounds to h AMCase was constructed, and we discuss the structure–activity relationships of the compounds we identified, suggested by the model and the actual inhibitory activities of the compounds.