Abstract
Mitogen-activated protein kinase phosphatase 1 is a tyrosine phosphatase superfamily member that dephosphorylates and inactivates mitogen-activated protein kinase substrates, such as p38, c-Jun-N-terminal kinase, and extracellular signal-related kinase. These mitogen-activated protein kinase substrates regulate many cellular processes associated with human diseases. In spite of this potential as a molecular target for chemotherapy, however, pharmacologically tractable inhibitors of mitogen-activated protein kinase phosphatase-1 have yet to be developed. Based on the results from a high-throughput screen for small molecule inhibitors of mitogen-activated protein kinase phosphatase-1, we designed, synthesized, and evaluated a focused library in an effort to further understand the structural requirements for mitogen-activated protein kinase phosphatase-1 inhibitory activity.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Cell Cycle Proteins / antagonists & inhibitors*
-
Cell Cycle Proteins / metabolism*
-
Dual Specificity Phosphatase 1
-
Enzyme Activation
-
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
-
Extracellular Signal-Regulated MAP Kinases / metabolism
-
Humans
-
Immediate-Early Proteins / antagonists & inhibitors*
-
Immediate-Early Proteins / metabolism*
-
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
JNK Mitogen-Activated Protein Kinases / metabolism
-
Peptide Library*
-
Phosphoprotein Phosphatases / antagonists & inhibitors*
-
Phosphoprotein Phosphatases / metabolism*
-
Phosphorylation
-
Protein Kinase Inhibitors / chemical synthesis*
-
Protein Kinase Inhibitors / metabolism
-
Protein Kinase Inhibitors / pharmacology
-
Protein Phosphatase 1
-
Protein Tyrosine Phosphatases / antagonists & inhibitors*
-
Protein Tyrosine Phosphatases / metabolism*
-
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
Cell Cycle Proteins
-
Immediate-Early Proteins
-
Peptide Library
-
Protein Kinase Inhibitors
-
Extracellular Signal-Regulated MAP Kinases
-
JNK Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
Phosphoprotein Phosphatases
-
Protein Phosphatase 1
-
DUSP1 protein, human
-
Dual Specificity Phosphatase 1
-
Protein Tyrosine Phosphatases