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

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

  • Medchemcomm. 2017 Aug 25;8(9):1850-1855. doi: 10.1039/c7md00278e.
Agnese C Pippione 1,  Antonella Federico 1,  Alex Ducime 1,  Stefano Sainas 1,  Donatella Boschi 1,  Alessandro Barge 1,  Elisa Lupino 2,  Marco Piccinini 2,  Michael Kubbutat 3,  Jean-Marie Contreras 4,  Christophe Morice 4,  Salam Al-Karadaghi 5,  Marco L Lolli 1
Affiliations

Affiliations

  • 1 Department of Science and Drug Technology , University of Torino , via Pietro Giuria 9 , 10125 Torino , Italy.
  • 2 Department of Oncology , University of Torino , via Michelangelo 27/B , 10126 Torino , Italy.
  • 3 ProQinase GmbH , Breisacher Str. 117 , 79106 Freiburg , Germany.
  • 4 Prestwick Chemical , 220 Boulevard Gonthier d'Andernach , 67400 Illkirch , France.
  • 5 SARomics Biostructures and Department of Biochemistry & Structural Biology , Lund University , Lund , Sweden.
PMID: 30108896 DOI: 10.1039/c7md00278e
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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