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
  • 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.