【摘 要】
：
Inhibition ofT-cell activation is the most efficient way to prevent transplant rejection.Among the immunosuppressants currently on the market,only calcineurin inhibitors (CNIs) inhibit specifically T-
【机 构】
：
Novartis Institutes for Biomedical Research Switzerland
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Inhibition ofT-cell activation is the most efficient way to prevent transplant rejection.Among the immunosuppressants currently on the market,only calcineurin inhibitors (CNIs) inhibit specifically T-cell activation,but their long term use is associated with side-effects (nephrotoxicity and cardiovascular side-effects).AEB071 is the first LMW inhibitor preventing T-cell activation via a calcineurin-independent pathway.AEB071 inhibits all classical and novel protein kinase C isotypes.Herein,we present the case story of AEB071 including the medicinal chemistry approaches,critical PK properties of the compound,preclinical data including in vivo models in rodents and non-human primates as well as positive proof-of-concept results obtained with AEB071 in psoriasis patients.Finally,we will also discuss the need of inhibition of multiple PKC isotypes versus specific inhibition of individual PKCs,namely PKC,to effectively suppress alloimmune responses.
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