Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10591488 | Bioorganic & Medicinal Chemistry Letters | 2013 | 7 Pages |
Abstract
A novel series of p38 MAP kinase inhibitors with high selectivity for the p38α isoform over the other family members including the highly homologous p38β isoform has been identified. X-ray co-crystallographic studies have revealed an unprecedented kinase binding mode in p38α for representative analogs, 5c and 9d, in which a Leu108/Met109 peptide flip occurs within the p38α hinge region. Based on these findings, a general strategy for the rational design of additional promising p38α isoform selective inhibitors by targeting this novel binding mode is proposed.
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Organic Chemistry
Authors
Stephen T. Wrobleski, Shuqun Lin, T.G. Murali Dhar, Alaric J. Dyckman, Tianle Li, Sidney Pitt, Rosemary Zhang, Yi Fan, Arthur M. Doweyko, John S. Tokarski, Kevin F. Kish, Susan E. Kiefer, John S. Sack, John A. Newitt, Mark R. Witmer, Murray McKinnon,