Document Report Card

ID: ALA3259539

Journal: J Med Chem

Title: A fragment-based method to discover irreversible covalent inhibitors of cysteine proteases.

Authors: Kathman SG, Xu Z, Statsyuk AV.

Abstract: A novel fragment-based drug discovery approach is reported which irreversibly tethers drug-like fragments to catalytic cysteines. We attached an electrophile to 100 fragments without significant alterations in the reactivity of the electrophile. A mass spectrometry assay discovered three nonpeptidic inhibitors of the cysteine protease papain. The identified compounds display the characteristics of irreversible inhibitors. The irreversible tethering system also displays specificity: the three identified papain inhibitors did not covalently react with UbcH7, USP08, or GST-tagged human rhinovirus 3C protease.

CiteXplore: 24870364

DOI: 10.1021/jm500345q