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Synthesis and Biological Activity of a Focused Library of Mitogen‐activated Protein Kinase Phosphatase Inhibitors
Author(s) -
Arnold David M.,
Foster Caleb,
Huryn Donna M.,
Lazo John S.,
Johnston Paul A.,
Wipf Peter
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00474.x
Subject(s) - mitogen activated protein kinase kinase , protein kinase a , c raf , map kinase kinase kinase , mitogen activated protein kinase , ask1 , map2k7 , phosphatase , cyclin dependent kinase 9 , protein tyrosine phosphatase , cyclin dependent kinase 2 , microbiology and biotechnology , protein kinase r , biochemistry , chemistry , kinase , biology , phosphorylation
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.