2. Academic Validation
  3. Design, synthesis and anti-breast cancer evaluation of biaryl pyridine analogues as potent RSK inhibitors

Design, synthesis and anti-breast cancer evaluation of biaryl pyridine analogues as potent RSK inhibitors

  • Bioorg Med Chem Lett. 2022 Mar 1;59:128565. doi: 10.1016/j.bmcl.2022.128565.
Yi-Man Cui 1,  Wei Li 2,  Tian-Ze Shen 1,  Yong-Xing Tao 1,  Biao-Qi Liu 1,  Xiao-Li Li 1,  Rui-Han Zhang 1,  De-Wei Jiang 3,  Wei-Lie Xiao 4
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
  • 2 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Sciences, The University of the Chinese Academy of Sciences, Kunming 650201, China.
  • 3 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Sciences, The University of the Chinese Academy of Sciences, Kunming 650201, China. Electronic address: [email protected].
  • 4 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China. Electronic address: [email protected].
PMID: 35065234 DOI: 10.1016/j.bmcl.2022.128565
Abstract

In order to discover and develop the new RSK kinase inhibitor, 50 pyridyl biaryl derivatives were designed and synthesized with LJH685 as the lead compound and their anti-tumor ability was tested. The results showed that the ability of 7d compound to inhibit the phosphorylation of YB-1 was comparable to that of LJH685. Among them, after preliminary screening, compound 7d showed good activity in inhibiting cell proliferation. Therefore, we took 7d as an example and performed molecular docking analysis on it. Judging from the overlapping combination diagram with LJH685, the results have verified that compound 7d has a similar skeleton to LJH685 and has a similar docking effect with RSK. Therefore, compound 7d is in line with the RSK inhibitor we designed and could be developed to a promising anti-tumor drug in the future.

Keywords

Breast Cancer; LJH685; RSK inhibitor; Structure-activity relationship; YB-1 phosphorylation.

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