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

ABSTRACT: The NF-?B signaling pathway is a validated oncological target. Here, we applied scaffold hopping to IMD-0354, a presumed IKK? 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-?B pathway. However, both 4 and IMD-0354, being potent inhibitors of the canonical NF-?B pathway, were found to be inactive in human IKK? enzyme assays.

SUBMITTER: Pippione AC

PROVIDER: S-EPMC6084005 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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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 C AC Federico Antonella A Ducime Alex A Sainas Stefano S Boschi Donatella D Barge Alessandro A Lupino Elisa E Piccinini Marco M Kubbutat Michael M Contreras Jean-Marie JM Morice Christophe C Al-Karadaghi Salam S Lolli Marco L ML

MedChemComm 20170825 9

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. ...[more]

PMID: 30108896

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