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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Identification of a novel competitive inhibitor of p38alpha MAPK by a human PBMC screen.

The pro-inflammatory cytokines TNF-alpha and IL-1beta are two of the important mediators involved in the several chronic inflammatory diseases. We used the release of TNF-alpha and IL-1beta from lipopolysaccharide-stimulated human PBMC as inflammatory indexes to discover the potential anti-inflammatory candidates. Among near 500 chemical compounds, MT4 had the suppressive action on the release of TNF-alpha and IL-1beta in PBMC with IC(50) values of 22 and 44nM, respectively. After verified the MT4 inhibitory mechanism, the results revealed that p38alpha and p38beta MAPK activity was inhibited by MT4 with an IC(50) value of 0.13 and 0.55muM, respectively. Further characterization of enzyme kinetics showed the binding mode of MT4 was competitive with the ATP substrate- binding site of p38alpha MAPK.[1]


  1. Identification of a novel competitive inhibitor of p38alpha MAPK by a human PBMC screen. Liu, Y.C., Ko, C.C., Cheng, F.C., Huang, P.T., Lou, K.L., Chow, L.P. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
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