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.
Technological Platform Physical Chemistry and characterization
Facility/equipment: Technological Platform
Mortier, J., Frederick, R., Pochet, L., Wouters, J., Masereel, B., Ganeff, C., Remouchamps, C., Piette, J., Dejardin, E., & Talaga, P. (2010). Pyrazolo[4,3-c]isoquinolines as potential inhibitors of NF-κB activation. Biochemical Pharmacology, 79(10), 1462-1472. https://doi.org/10.1016/j.bcp.2010.01.007