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

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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
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2017-08-25 00:00:00 , DOI: 10.1039/c7md00278e
Agnese C. Pippione _{1,

2,

3,

4} , Antonella Federico _{1,

2,

3,

4} , Alex Ducime _{1,

2,

3,

4} , Stefano Sainas _{1,

2,

3,

4} , Donatella Boschi _{1,

2,

3,

4} , Alessandro Barge _{1,

2,

3,

4} , Elisa Lupino _{2,

4,

5,

6} , Marco Piccinini _{2,

4,

5,

6} , Michael Kubbutat _{7,

8,

9} , Jean-Marie Contreras _{10,

11,

12} , Christophe Morice _{10,

11,

12} , Salam Al-Karadaghi _{13,

14,

15,

16} , Marco L. Lolli _{1,

2,

3,

4}

Affiliation

Department of Science and Drug Technology
University of Torino
10125 Torino
Italy
Department of Oncology
10126 Torino
ProQinase GmbH
79106 Freiburg
Germany
Prestwick Chemical
67400 Illkirch
France
SARomics Biostructures and Department of Biochemistry & Structural Biology
Lund University
Lund
Sweden

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.

中文翻译：

4-羟基-N- [3,5-双（三氟甲基）苯基] -1,2,5-噻二唑-3-羧酰胺：一种典型的NF-κB级联抑制剂

NF-κB信号通路是经过验证的肿瘤学靶标。在这里，我们将支架跳跃应用于假定的IKKβ抑制剂IMD-0354，并鉴定出4-羟基-N- [3,5-双（三氟甲基）苯基] -1,2,5-噻二唑-3-羧酰胺（4）作为NF-κB途径的nM抑制剂。但是，在人IKKβ酶检测中发现4和IMD-0354（均是典型的NF-κB途径的有效抑制剂）均无活性。

更新日期：2017-09-21

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