Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832002, China.
Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832002, China.
Bioorg Med Chem. 2018 Jul 23;26(12):3491-3501. doi: 10.1016/j.bmc.2018.05.024. Epub 2018 May 17.
Cyclin-dependent kinase 2 (CDK2) plays a key role in eukaryotic cell cycle progression which could facilitate the transition from G1 to S phase. The dysregulation of CDK2 is closely related to many cancers. CDK2 is utilized as one of the most studied kinase targets in oncology. In this article, 24 benzamide derivatives were designed, synthesized and investigated for the inhibition activity against CDK2. Our results revealed that the compound 25 is a potent CDK2 inhibitor exhibiting a broad spectrum anti-proliferative activity against several human breast cancer cells. Additionally, compound 25 could block cell cycle at G0 or G1 and induce significant apoptosis in MDA-MB-468 cells. These findings highlight a rationale for further development of CDK2 inhibitors to treat human breast cancer.
细胞周期蛋白依赖性激酶 2（CDK2）在真核细胞周期进程中发挥关键作用，可促进细胞从 G1 期向 S 期过渡。CDK2 的失调与许多癌症密切相关。CDK2 被用作肿瘤学中研究最多的激酶靶标之一。在本文中，设计、合成了 24 种苯甲酰胺衍生物，并研究了它们对 CDK2 的抑制活性。我们的结果表明，化合物 25 是一种有效的 CDK2 抑制剂，对几种人乳腺癌细胞具有广谱的抗增殖活性。此外，化合物 25 可使 MDA-MB-468 细胞阻滞在 G0 或 G1 期，并诱导明显的细胞凋亡。这些发现为进一步开发 CDK2 抑制剂治疗人类乳腺癌提供了依据。
