Details

Autor(en) / Beteiligte

• Han, Yongxin
• Giroux, André
• Grimm, Erich L.
• Aspiotis, Renée
• Francoeur, Sébastien
• Bayly, Christopher I.
• Mckay, Daniel J.
• Roy, Sophie
• Xanthoudakis, Steve
• Vaillancourt, John P.
• Rasper, Dita M.
• Tam, John
• Tawa, Paul
• Thornberry, Nancy A.
• Paterson, Erin P.
• Garcia-Calvo, Margarita
• Becker, Joseph W.
• Rotonda, Jennifer
• Nicholson, Donald W.
• Zamboni, Robert J.

Titel

Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2004-02, Vol.14 (3), p.805-808

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• The discovery of a series of potent, selective and reversible dipeptidyl caspase-3 inhibitors are reported. The iterative discovery process of using combinatorial chemistry, parallel synthesis, moleculare modelling and structural biology will be discussed. The discovery of a series of potent, selective and reversible caspase-3 inhibitors employing combinatorial chemistry, structural biology and molecular modeling is described. Compound 16, for example, is a potent inhibitor against rh-caspase-3 with an IC 50 of 5 nM, selective against rh-caspase-1 (IC 50: 1600 nM), rh-caspase-7 (IC 50: 120 nM) and rh-caspase-8 (IC 50: 490 nM), and active against camptothecin induced apoptosis in NT2 cells with an IC 50 of 1 μM.