-乙酰基-3-氨基吡唑通过选择性抑制NF-κB诱导激酶（NIK）来阻断非经典NF-κB信号级联反应。
-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK.
作者信息
Pippione Agnese C, Sainas Stefano, Federico Antonella, Lupino Elisa, Piccinini Marco, Kubbutat Michael, Contreras Jean-Marie, Morice Christophe, Barge Alessandro, Ducime Alex, Boschi Donatella, 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 . Email:
Department of Oncology , University of Torino , via Michelangelo 27/B , 10126 Torino , Italy.
出版信息
Medchemcomm. 2018 Apr 12;9(6):963-968. doi: 10.1039/c8md00068a. eCollection 2018 Jun 1.
Abstract
NF-κB-inducing kinase (NIK), an oncogenic drug target that is associated with various cancers, is a central signalling component of the non-canonical pathway. A blind screening process, which established that amino pyrazole related scaffolds have an effect on IKKbeta, led to a optimization process that identified the aminopyrazole as a low μM selective NIK inhibitor. Compound effectively inhibited the NIK-dependent activation of the NF-κB pathway in tumour cells, confirming its selective inhibitory profile.
摘要
核因子κB诱导激酶（NIK）是一种与多种癌症相关的致癌药物靶点，是非经典途径的核心信号成分。一项盲筛过程确定了氨基吡唑相关支架对IKKβ有作用，进而引发了优化过程，该过程确定氨基吡唑为低 microM 选择性 NIK 抑制剂。该化合物有效抑制肿瘤细胞中 NF-κB 途径的 NIK 依赖性激活，证实了其选择性抑制特性。
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