Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-κB activation
2010
In this work, we aimed to build a 3D-model of NIK and to study the binding of pyrazolo[4,3-c]isoquinolines with a view to highlight the structural elements responsible for their inhibitory potency. However, in the course of this work, we unexpectedly found that the pyrazolo[4,3-c]isoquinolines initially reported as NIK inhibitors were neither inhibitors of this enzyme nor of the alternative NF-κB pathway, but were in fact inhibitors of another kinase, the TGF-β activated kinase 1 (TAK1) which is involved in the classical NF-κB pathway. © 2010 Elsevier Inc. All rights reserved.
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