The NF-κB signaling pathway is a validated oncological target. Here, we applied scaffold hopping to IMD-0354, a presumed IKKβ inhibitor, and identified 4-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide (4) as a nM-inhibitor of the NF-κB pathway. However, both 4 and IMD-0354, being potent inhibitors of the canonical NF-κB pathway, were found to be inactive in human IKKβ enzyme assays.

4-Hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a novel inhibitor of the canonical NF-κB cascade

PIPPIONE, Agnese Chiara;FEDERICO, ANTONELLA;DUCIME, ALEX;SAINAS, STEFANO;BOSCHI, Donatella;BARGE, Alessandro;LUPINO, Elisa;PICCININI, Marco;AL KARADAGHI, SALAM;LOLLI, Marco Lucio
2017

Abstract

The NF-κB signaling pathway is a validated oncological target. Here, we applied scaffold hopping to IMD-0354, a presumed IKKβ inhibitor, and identified 4-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide (4) as a nM-inhibitor of the NF-κB pathway. However, both 4 and IMD-0354, being potent inhibitors of the canonical NF-κB pathway, were found to be inactive in human IKKβ enzyme assays.
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http://pubs.rsc.org/en/Content/ArticleLanding/2017/MD/C7MD00278E#!divAbstract
KINASE-BETA-INHIBITOR, CRYSTAL-STRUCTURE, DRUG DESIGN, MOUSE MODEL, IMD-0354, MICE, PROLIFERATION, INFLAMMATION, ACTIVATION, DISCOVERY
Pippione, Agnese C.; Federico, Antonella; Ducime, Alex; Sainas, Stefano; Boschi, Donatella; Barge, Alessandro; Lupino, Elisa; Piccinini, Marco; Kubbutat, Michael; Contreras, Jean-Marie; Morice, Christophe; Al-Karadaghi, Salam; Lolli, Marco L.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1648121
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