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

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