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 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.

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

Agnese C. Pippione
First
;
Stefano Sainas;Antonella Federico;Elisa Lupino;Marco Piccinini;Alessandro Barge;Alex Ducime;Donatella Boschi;Marco L. Lolli
Last
2018-01-01

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 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.
2018
9
6
963
968
https://pubs.rsc.org/en/content/articlelanding/2018/md/c8md00068a#!divAbstract
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071728/
https://europepmc.org/articles/pmc6071728?pdf=render
https://pubmed.ncbi.nlm.nih.gov/30108985/
KAPPA-B, BREAST-CANCER, MULTIPLE-MYELOMA, aminopyrazoles, NF-kB cascade, NIK inhibitor
Agnese C. Pippione, Stefano Sainas, Antonella Federico, Elisa Lupino, Marco Piccinini, Michael Kubbutat, Jean-Marie Contreras, Christophe Morice, Alessandro Barge, Alex Ducime, Donatella Boschi, Salam Al-Karadaghi, Marco L. Lolli
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1666293
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