Noncovalent Tripeptidyl Benzyl- and Cyclohexyl-Amine Inhibitors of the Cysteine Protease Caspase-1
Noncovalent Tripeptidyl Benzyl- and Cyclohexyl-Amine Inhibitors of the Cysteine Protease Caspase-1
Löser, R.; Abbenante, G.; Madala, P. K.; Halili, M.; Le, G. T.; Fairlie, D. P.
Potent and noncovalent inhibitors of caspase-1 were produced by incorporating a secondary amine (reduced amide) isostere in place of the conventional electrophile (e.g., aldehyde) that normally confers high potency to cysteine protease inhibitors. Benzyl- or cyclohexylamines produced potent, reversible, and competitive inhibitors that were selective for caspase-1 (e.g., Ki=47 nM) over caspases 3 and 8with minimal cytotoxicity. Unlike most cysteine protease inhibitors, these compounds do not react covalently and indiscriminately with thiols.
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Journal of Medicinal Chemistry 53(2010), 2651-2655
DOI: 10.1021/jm901790w
Cited 12 times in Scopus
Permalink: https://www.hzdr.de/publications/Publ-15015