Noncovalent tripeptidyl benzyl- And cyclohexyl-amine inhibitors of the cysteine protease caspase-1

Reik Löser, Giovanni Abbenante, Praveen K. Madala, Maria Halili, Giang T. Le, David P. Fairlie

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11 Citations (Scopus)

Abstract

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 8 with minimal cytotoxicity. Unlike most cysteine protease inhibitors, these compounds do not react covalently and indiscriminately with thiols.

Original languageEnglish
Pages (from-to)2651-2655
Number of pages5
JournalJournal of Medicinal Chemistry
Volume53
Issue number6
DOIs
Publication statusPublished - 25 Mar 2010
Externally publishedYes

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