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

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Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes.

A series of novel maleimide-based inhibitors of protein kinase C (PKC) were designed, synthesized, and evaluated. AEB071 (1) was found to be a potent, selective inhibitor of classical and novel PKC isotypes. 1 is a highly efficient immunomodulator, acting via inhibition of early T cell activation. The binding mode of maleimides to PKCs, proposed by molecular modeling, was confirmed by X-ray analysis of 1 bound in the active site of PKCalpha.[1]

References

  1. Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. Wagner, J., von Matt, P., Sedrani, R., Albert, R., Cooke, N., Ehrhardt, C., Geiser, M., Rummel, G., Stark, W., Strauss, A., Cowan-Jacob, S.W., Beerli, C., Weckbecker, G., Evenou, J.P., Zenke, G., Cottens, S. J. Med. Chem. (2009) [Pubmed]
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