N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK. Issue 6 (4th May 2018)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: MedChemComm. Volume 9:Issue 6(2018)
• Page Start: 963
• Page End: 968
• Publication Date: 2018-05-04
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c8md00068a
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Resulting from hit-to-lead optimization, the aminopyrazole3a is a NIK inhibitor selective over 44 kinases. 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 aminopyrazole3a as a low μM selective NIK inhibitor. Compound3a effectively inhibited the NIK-dependent activation of the NF-κB pathway in tumour cells, confirming its selective inhibitory profile.