The mitogen-activated protein kinases (MAPK) p38a is a serine/theronine kinase that serves an important role in the production of inflammatory cytokines including necrosis factor alpha (THFa) and interleukin-1 beta (1L-1�). MAPK-substrate specificity has been shown to be mediated through docking interactions involving substrate docking motifs that interact with kinase recruitment domains. Blocking docking interactions between kinase network partners is a promising alternative approach to targeting the ATP-binding site for selectively inhibiting kinase signaling. Here we report the identification of a small molecule, cell permeable covalent p38a recruitment site (DRS) probe. Using �click� chemistry, this probe can be used to fluorescently to label p38a. An assay employing this probe was used to identify the natural product rooperol as a p38a DRS inhibitor (IC50= 18.6 �M).

Assay for p38α recruitment site binders: Identification of rooperol as a novel p38α kinase inhibitor

245th National Meeting (2013)

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