N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK
N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK
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DOI：
10.1039/c8md00068a
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发表时间：
2018-06-01
期刊：
影响因子：
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通讯作者：
Lolli, Marco L.
中科院分区：
文献类型：
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作者：
Pippione, Agnese C.;Sainas, Stefano;Lolli, Marco L.
核因子-kappaB诱导激酶(NIK)是一种与多种癌症相关的致癌药物靶点，是非经典途径的中心信号成分。盲法筛选过程确定了氨基吡唑相关支架对IKKβ有影响，导致了一种点击到领先的优化过程，确定了氨基吡唑3a是一种低M选择性的Nik抑制剂。化合物3a有效地抑制了肿瘤细胞中依赖Nik的核因子-kappaB途径的激活，证实了其选择性抑制谱。
NF-kappa B-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 hit-to-lead optimization process that identified the aminopyrazole 3a as a low M selective NIK inhibitor. Compound 3a effectively inhibited the NIK-dependent activation of the NF-kappa B pathway in tumour cells, confirming its selective inhibitory profile.