N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK?

MedChemComm Pub Date: 2018-04-12 DOI: 10.1039/C8MD00068A

Abstract

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.

Graphical abstract: N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK
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