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

Loser, Reik, Abbenante, Giovanni, Madala, Praveen K., Halili, Maria, Le, Giang T. and Fairlie, David P. (2010) Noncovalent tripeptidyl benzyl- And cyclohexyl-amine inhibitors of the cysteine protease caspase-1. Journal of Medicinal Chemistry, 53 6: 2651-2655. doi:10.1021/jm901790w


Author Loser, Reik
Abbenante, Giovanni
Madala, Praveen K.
Halili, Maria
Le, Giang T.
Fairlie, David P.
Title Noncovalent tripeptidyl benzyl- And cyclohexyl-amine inhibitors of the cysteine protease caspase-1
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
1520-4804
Publication date 2010-03-25
Sub-type Article (original research)
DOI 10.1021/jm901790w
Volume 53
Issue 6
Start page 2651
End page 2655
Total pages 5
Place of publication Washington, D.C., U.S.A.
Publisher American Chemical Society
Collection year 2011
Language eng
Formatted 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.
© 2010 American Chemical Society.
Keyword Cathepsin-S
Arylaminoethyl amides
Proteolytic-enzymes
Drug design
Validation
Constants
Binding
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 04 Apr 2010, 00:03:27 EST