Drug Design & Discovery Center, University of Namur, FUNDP, Belgium.
Biochem Pharmacol. 2010 May 15;79(10):1462-72. doi: 10.1016/j.bcp.2010.01.007. Epub 2010 Jan 21.
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-kappaB pathway, but were in fact inhibitors of another kinase, the TGF-beta activated kinase 1 (TAK1) which is involved in the classical NF-kappaB pathway.
在这项工作中，我们的目的是构建 NIK 的 3D 模型，并研究吡唑并[4,3-c]异喹啉与该模型的结合情况，以期突出其抑制效力的结构要素。然而，在这项工作的过程中，我们意外地发现，最初被报道为 NIK 抑制剂的吡唑并[4,3-c]异喹啉既不是这种酶的抑制剂，也不是替代 NF-kappaB 途径的抑制剂，而是实际上是另一种激酶 TGF-beta 激活激酶 1（TAK1）的抑制剂，TAK1 激酶参与经典的 NF-kappaB 途径。
