Acyl dipeptides as reversible caspase inhibitors. Part 2: further optimization.
A new structural class of broad spectrum caspase inhibitors was optimized for its activity against caspases 1, 3, 6, 7, and 8. The most potent compound had low nanomolar broad spectrum activity, in particular, single digit nanomolar inhibitory activity against caspase 8.
Linton
Steven D
SD
Idun Pharmaceuticals, Inc., 9380 Judicial Drive, San Diego, CA 92121, USA. slinton@idun.com
Karanewsky
Donald S
DS
Ternansky
Robert J
RJ
Chen
Ning
N
Guo
Xian
X
Jahangiri
Kathy G
KG
Kalish
Vincent J
VJ
Meduna
Steven P
SP
Robinson
Edward D
ED
Ullman
Brett R
BR
Wu
Joe C
JC
Pham
Brian
B
Kodandapani
Lalitha
L
Smidt
Robert
R
Diaz
Jose-Luis
JL
Fritz
Lawrence C
LC
von Krosigk
U
U
Roggo
Silvio
S
Schmitz
Albert
A
Tomaselli
Kevin J
KJ
D000215:Acylation; D061945:Caspase Inhibitors; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D061945:Caspase Inhibitors; D004151:Dipeptides; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007527:Isoenzymes; D009842:Oligopeptides