| Literature DB >> 23746475 |
Stephen T Wrobleski1, 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, Joel C Barrish, John H Dodd, Gary L Schieven, Katerina Leftheris.
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.Entities:
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Year: 2013 PMID： 23746475 DOI： 10.1016/j.bmcl.2013.05.047
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823