Anti-MAPKAPK2 monoclonal antibody, clone 4C9

We have identified a novel series of substituted N,N'-diarylurea p38 alpha inhibitors. The inhibitory activity of the target compounds against the enzyme p38 alpha, MAPKAPK2 in BHK cells, TNF-alpha release in LPS-stimulated THP-1 cells and p38 alpha binding experiments were tested. Among these compounds, 25a inhibited the p38 alpha enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 x 10(-8) and appears to be the most promising one in the series.

The p38 mitogen-activated protein kinase (p38MAPK) pathway has been implicated in a variety of pathological conditions including inflammation and metastasis. Post-transcriptional regulation of genes harboring adenine/uridine-rich elements (AREs) in their 3-untranslated region (3-UTR) is controlled by MAPK-activated protein kinase 2 (MAPKAPK2 or MK2), a downstream substrate of the p38MAPK. In response to diverse extracellular stimuli, MK2 influences crucial signaling events, regulates inflammatory cytokines, transcript stability and critical cellular processes. Expression of genes involved in these vital cellular cascades is controlled by subtle interactions in underlying molecular networks and post-transcriptional gene regulation that determines transcript fate in association with RNA-binding proteins (RBPs). Several RBPs associate with the 3-UTRs of the target transcripts and regulate their expression via modulation of transcript stability. Although MK2 regulates important cellular phenomenon, yet its biological significance in tumor progression has not been well elucidated till date. In this review, we have highlighted in detail the importance of MK2 as the master regulator of RBPs and its role in the regulation of transcript stability, tumor progression, as well as the possibility of use of MK2 as a therapeutic target in tumor management.