Novel ATP competitive MK2 inhibitors with potent biochemical and cell-based activity throughout the series
作者
Oubrie, A; Kaptein, A; de Zwart, E; Hoogenboom, N; Goorden, R; van de Kar, B; van Hoek, M; de Kimpe, V; van der Heijden, R; Borsboom, J; Kazemier, B; de Roos, J; Scheffers, M; Lommerse, J; Schultz-Fademrecht, C; Barf, T
[摘要]：Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNF alpha is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series. (C) 2011 Elsevier Ltd. All rights reserved.
