4-羟基-2-[3,5-双（三氟甲基）苯基]-1,2,5-噻二唑-3-甲酰胺：一种经典核因子κB级联反应的新型抑制剂。
4-Hydroxy--[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a novel inhibitor of the canonical NF-κB cascade.
作者信息
Pippione Agnese C, Federico Antonella, Ducime Alex, Sainas Stefano, Boschi Donatella, Barge Alessandro, Lupino Elisa, Piccinini Marco, Kubbutat Michael, Contreras Jean-Marie, Morice Christophe, Al-Karadaghi Salam, Lolli Marco L
机构信息
Department of Science and Drug Technology , University of Torino , via Pietro Giuria 9 , 10125 Torino , Italy.
Department of Oncology , University of Torino , via Michelangelo 27/B , 10126 Torino , Italy.
出版信息
Medchemcomm. 2017 Aug 25;8(9):1850-1855. doi: 10.1039/c7md00278e. eCollection 2017 Sep 1.
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--[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide () as a nM-inhibitor of the NF-κB pathway. However, both and IMD-0354, being potent inhibitors of the canonical NF-κB pathway, were found to be inactive in human IKKβ enzyme assays.
摘要
核因子-κB（NF-κB）信号通路是一个经过验证的肿瘤学靶点。在此，我们对假定的IKKβ抑制剂IMD-0354进行了骨架跃迁，并鉴定出4-羟基--[3,5-双（三氟甲基）苯基]-1,2,5-噻二唑-3-甲酰胺（）作为NF-κB通路的纳摩尔级抑制剂。然而，发现 和IMD-0354作为经典NF-κB通路的强效抑制剂，在人IKKβ酶检测中均无活性。
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