Abstract
Two cyclopeptidic Smac mimetics, 2 and 3, were designed and synthesized. These two compounds bind to XIAP and cIAP-1/2 with low nanomolar affinities, and restore the activities of caspase-9 and caspase-3/-7 inhibited by XIAP. Compound 2 potently inhibits cancer cell growth and is 5-8 times more potent than the initial lead compound.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / pharmacology
-
Apoptosis
-
Caspase 3 / metabolism
-
Caspase 7 / metabolism
-
Caspase 9 / metabolism
-
Humans
-
Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
-
Inhibitor of Apoptosis Proteins / metabolism
-
Oligopeptides / chemical synthesis
-
Oligopeptides / chemistry*
-
Oligopeptides / pharmacology
-
Peptides, Cyclic / chemical synthesis
-
Peptides, Cyclic / chemistry*
-
Peptides, Cyclic / pharmacology
-
Protein Binding
-
Protein Structure, Tertiary
-
Triazoles / chemical synthesis
-
Triazoles / chemistry*
-
Triazoles / pharmacology
-
X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors
-
X-Linked Inhibitor of Apoptosis Protein / metabolism
Substances
-
Antineoplastic Agents
-
Inhibitor of Apoptosis Proteins
-
Oligopeptides
-
Peptides, Cyclic
-
SM 162
-
SMAC peptide
-
Triazoles
-
X-Linked Inhibitor of Apoptosis Protein
-
Caspase 3
-
Caspase 7
-
Caspase 9