MedChemComm p. 963 - 968 (2018)
Update date:2022-08-02
Topics:
Pippione, Agnese C.
Sainas, Stefano
Federico, Antonella
Lupino, Elisa
Piccinini, Marco
Kubbutat, Michael
Contreras, Jean-Marie
Morice, Christophe
Barge, Alessandro
Ducime, Alex
Boschi, Donatella
Al-Karadaghi, Salam
Lolli, Marco L.
NF-κB-inducing kinase (NIK), an oncogenic drug target that is associated with various cancers, is a central signalling component of the non-canonical pathway. A blind screening process, which established that amino pyrazole related scaffolds have an effect on IKKbeta, led to a hit-to-lead optimization process that identified the aminopyrazole 3a as a low μM selective NIK inhibitor. Compound 3a effectively inhibited the NIK-dependent activation of the NF-κB pathway in tumour cells, confirming its selective inhibitory profile.
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