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

…, G Abbenante, PK Madala, M Halili, GT Le…

Index: Le, Giang Thanh; Abbenante, Giovanni; Madala, Praveen K.; Hoang, Huy N.; Fairlie, David P. Journal of the American Chemical Society, 2006 , vol. 128, # 38 p. 12396 - 12397

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Citation Number: 17

Abstract

Potent and noncovalent inhibitors of caspase-1 were produced by incorporating a secondary amine (reduced amide) isostere in place of the conventional electrophile (eg, 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 (eg, K i= 47 nM) over caspases 3 and 8 with minimal cytotoxicity. Unlike ...

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