Structure–activity relationship and pharmacokinetic studies of sotrastaurin (AEB071), a promising novel medicine for prevention of graft rejection and treatment of …

…, G Weckbecker, JP Evenou, G Zenke…

Index: Wagner, Juergen; Von Matt, Peter; Faller, Bernard; Cooke, Nigel G.; Albert, Rainer; Sedrani, Richard; Wiegand, Hansjoerg; Jean, Christian; Beerli, Christian; Weckbecker, Gisbert; Evenou, Jean-Pierre; Zenke, Gerhard; Cottens, Sylvain Journal of Medicinal Chemistry, 2011 , vol. 54, # 17 p. 6028 - 6039

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Citation Number: 30

Abstract

Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure–activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to ...