4-Hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a novel inhibitor of the canonical NF-κB cascade.
Agnese C PippioneAntonella FedericoAlex DucimeStefano SainasDonatella BoschiAlessandro BargeElisa LupinoMarco PiccininiMichael KubbutatJean-Marie ContrerasChristophe MoriceSalam Al-KaradaghiMarco Lucio LolliPublished in: MedChemComm (2017)
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.
Keyphrases
- signaling pathway
- pi k akt
- lps induced
- nuclear factor
- oxidative stress
- induced apoptosis
- epithelial mesenchymal transition
- endothelial cells
- ionic liquid
- inflammatory response
- rectal cancer
- prostate cancer
- high throughput
- cell proliferation
- immune response
- induced pluripotent stem cells
- single cell
- pluripotent stem cells
- crystal structure