细胞周期蛋白依赖激酶2
体外
激酶
黑色素瘤
细胞周期蛋白依赖激酶
化学
细胞培养
细胞周期
细胞凋亡
生物测定
活力测定
虚拟筛选
细胞生长
蛋白激酶A
细胞
癌症研究
生物化学
生物
药物发现
遗传学
作者
Lihong Yang,Mukuo Wang,Beibei Li,Shangqin Xu,Jianping Lin
标识
DOI:10.1096/fj.202201217rr
摘要
Cyclin-dependent kinases 2 (CDK2) is a serine/threonine-protein kinase, which plays a key role in the regulation of cell cycle and is related to the occurrence and development of melanoma. In this study, we identified potent inhibitors for CDK2 by combining a multistage virtual screening strategy with bioassay validations. The biochemical activity of compounds was validated with ADP-Glo™ Kinase assay in vitro, and the results indicated that the biochemical activity of compound 1 (C1) was better than other selected compounds. Cell viability assay showed that the minimum inhibition concentration of C1 for CDK2 was lower than 4 μM. Further functional test results showed that C1 exerted significant antiproliferative, pro-apoptosis, and anti-migration activity in melanoma cell lines (A375 cells, WM35 cells, and A875 cells). Our findings suggested that the C1, virtually screened from compound libraries, as the novel inhibitor of CDK2, may be further developed as an effective therapeutic agent in the treatment of melanoma lines.
科研通智能强力驱动
Strongly Powered by AbleSci AI