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 hit-to-lead optimization process that identified the aminopyrazole 3a as a low μM selective NIK inhibitor. Compound 3a effectively inhibited the NIK-dependent activation of the NF-κB pathway in tumour cells, confirming its selective inhibitory profile.

中文翻译：

---

N-乙酰基-3-氨基吡唑通过选择性抑制 NIK 来阻断非典型 NF-kB 级联†

NF-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传导成分。盲选过程确定了氨基吡唑相关支架对 IKKbeta 具有影响，从而导致了命中到先导优化过程，将氨基吡唑3a鉴定为低 μM 选择性 NIK 抑制剂。化合物3a有效抑制肿瘤细胞中 NIK 依赖性 NF-κB 通路激活，证实了其选择性抑制特性。