Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: peptidomimetic replacement of the P(2) amino acid by 2-aminoaryl acids and other non-natural amino acids.
Bioorg Med Chem Lett
; 17(22): 6178-82, 2007 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-17889532
ABSTRACT
As a continuation of our SAR studies of dipeptidyl aspartyl-fmk as caspase inhibitors, we explored the replacement of the P(2) amino acid by a 2-aminoaryl acid or other non-natural amino acids. Several of these compounds, such as 6l and 6p, were found to have good activities with inhibition potencies of around 100 nM in a caspase-3 enzyme assay. EP1113, Z-Val-(2-aminobenzoyl)-Asp-fmk (9b), is identified as a potent broad-spectrum caspase inhibitor with IC(50) values of 6-60 nM in different caspases. EP1113 also has good activity in a cell apoptosis protection assay.
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Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Mimetismo Molecular
/
Dipeptídeos
/
Inibidores de Caspase
/
Aminoácidos
/
Cetonas
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article