Document Report Card

ID: ALA4257503

Journal: Medchemcomm

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

Authors: Pippione AC, Sainas S, Federico A, Lupino E, Piccinini M, Kubbutat M, Contreras JM, Morice C, Barge A, Ducime A, Boschi D, Al-Karadaghi S, Lolli ML.

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.

CiteXplore: 30108985

DOI: 10.1039/C8MD00068A