1610801-87-0Relevant academic research and scientific papers
A fragment-based method to discover irreversible covalent inhibitors of cysteine proteases
Kathman, Stefan G.,Xu, Ziyang,Statsyuk, Alexander V.
, p. 4969 - 4974 (2014/07/07)
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.
