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

Protein kinase Calpha and epsilon small-molecule targeted therapeutics: a new roadmap to two Holy Grails in drug discovery?

Protein kinase (PK)Calpha and epsilon are rational targets for cancer therapy. However, targeted experimental therapeutics that inhibit PKCalpha or epsilon are unavailable. The authors established recently that covalent modification of an active-site cysteine in human PKCepsilon, Cys452, by small molecules, for example 2-mercaptoethanolamine, is necessary and sufficient to render PKCepsilon kinase-dead. Cys452 is conserved in only eleven human protein kinase genes, including PKCalpha. Therefore, the design of small molecules that bind PKC active sites with an electrophile substituent positioned proximal to the Cys452 side chain may lead to targeted therapeutics that selectively inhibit PKCepsilon, PKCalpha or other PKC isozymes.[1]

References

  1. Protein kinase Calpha and epsilon small-molecule targeted therapeutics: a new roadmap to two Holy Grails in drug discovery? O'Brian, C.A., Chu, F., Bornmann, W.G., Maxwell, D.S. Expert review of anticancer therapy. (2006) [Pubmed]
 
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