4kiq

Publication Abstract from PubMed

A novel series of p38 MAP kinase inhibitors with high selectivity for the p38alpha isoform over the other family members including the highly homologous p38beta isoform has been identified. X-ray co-crystallographic studies have revealed an unprecedented kinase binding mode in p38alpha for representative analogs, 5c and 9d, in which a Leu108/Met109 peptide flip occurs within the p38alpha hinge region. Based on these findings, a general strategy for the rational design of additional promising p38alpha isoform selective inhibitors by targeting this novel binding mode is proposed.

The identification of novel p38alpha isoform selective kinase inhibitors having an unprecedented p38alpha binding mode.,Wrobleski ST, Lin S, Murali Dhar TG, Dyckman AJ, Li T, Pitt S, Zhang R, Fan Y, Doweyko AM, Tokarski JS, Kish KF, Kiefer SE, Sack JS, Newitt JA, Witmer MR, McKinnon M, Barrish JC, Dodd JH, Schieven GL, Leftheris K Bioorg Med Chem Lett. 2013 Jul 15;23(14):4120-6. doi: 10.1016/j.bmcl.2013.05.047., Epub 2013 May 23. PMID:23746475^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.