Abstract
Inhibitors of human methionine aminopeptidase type 2 (hMetAP2) are of interest as potential treatments for cancer. A new class of small molecule reversible inhibitors of hMetAP2 was discovered and optimized, the 4-aryl-1,2,3-triazoles. Compound 24, a potent inhibitor of cobalt-activated hMetAP2, also inhibits human and mouse endothelial cell growth. Using a mouse matrigel model, this reversible hMetAP2 inhibitor was also shown to inhibit angiogenesis in vivo.
MeSH terms
-
Aminopeptidases / antagonists & inhibitors*
-
Aminopeptidases / chemistry
-
Angiogenesis Inhibitors / chemical synthesis*
-
Angiogenesis Inhibitors / chemistry
-
Angiogenesis Inhibitors / pharmacology
-
Animals
-
Binding Sites
-
Biological Availability
-
Cell Proliferation / drug effects
-
Cells, Cultured
-
Cobalt / metabolism
-
Collagen
-
Crystallography, X-Ray
-
Drug Combinations
-
Endothelial Cells / cytology
-
Endothelial Cells / drug effects
-
Endothelium, Vascular / cytology
-
Enzyme Activation
-
Humans
-
Laminin
-
Metalloendopeptidases / antagonists & inhibitors*
-
Metalloendopeptidases / chemistry
-
Mice
-
Models, Molecular
-
Molecular Structure
-
Proteoglycans
-
Rats
-
Structure-Activity Relationship
-
Triazoles / chemical synthesis*
-
Triazoles / chemistry
-
Triazoles / pharmacology
Substances
-
Angiogenesis Inhibitors
-
Drug Combinations
-
Laminin
-
Proteoglycans
-
Triazoles
-
matrigel
-
Cobalt
-
Collagen
-
Aminopeptidases
-
methionine aminopeptidase 2
-
Metalloendopeptidases