Exploration of tricyclic heterocycles as core structures for RIOK2 inhibitors,RSC Medicinal Chemistry

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Exploration of tricyclic heterocycles as core structures for RIOK2 inhibitors
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2023-07-21 , DOI: 10.1039/d3md00209h
Huilan Xiong ₁ , Qiuchun Yu ₁ , Haowen Ma ₁ , Xiuwen Yu ₁ , Yifan Ouyang ₁ , Zhi-Min Zhang ₁ , Wei Zhou ₁ , Zhang Zhang ₁ , Qian Cai ₁

Affiliation

Right open reading frame kinase 2 (RIOK2) is an atypical kinase and has been proved to be involved in multiple human cancers including non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), glioblastoma and anemia. Although tremendous efforts have been devoted to the studies of RIOK2, its biological functions remain poorly understood. It is highly important to develop potent and selective RIOK2 inhibitors as potential research tools to elucidate its functions and as drug candidates for further therapies. We have previously identified a highly potent and selective RIOK2 inhibitor (CQ211). To confirm the importance of the “V-shaped” structure of CQ211 for binding with RIOK2, a variety of tricyclic compounds with different core structures instead of the [1,2,3]triazolo[4,5-c]quinolin-4-one core of CQ211 were designed, synthesized, and the binding affinities of these tricyclic heterocycles with RIOK2 were also evaluated.

中文翻译：

三环杂环作为 RIOK2 抑制剂核心结构的探索

右开放阅读框激酶2 （RIOK2）是一种非典型激酶，已被证明与多种人类癌症有关，包括非小细胞肺癌（NSCLC）、急性髓性白血病（AML）、胶质母细胞瘤和贫血。尽管人们对RIOK2的研究投入了巨大的努力，但其生物学功能仍然知之甚少。开发有效且选择性的 RIOK2 抑制剂作为阐明其功能的潜在研究工具以及作为进一步治疗的候选药物非常重要。我们之前已经鉴定出一种高效且选择性的 RIOK2 抑制剂 ( CQ211 )。为了证实CQ211的“V形”结构对于与RIOK2结合的重要性，多种具有不同核心结构的三环化合物代替了[1,2,3]三唑并[4,5- c ]喹啉-4-设计、合成了CQ211的一个核心，并评估了这些三环杂环与RIOK2的结合亲和力。

更新日期：2023-07-21

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