Roscovitine (Seliciclib,CYC202) is an effective inhibitor of Cdk2/cyclin E with an IC50 value of 0.1μM. Roscovitine also inhibits Cdk7/cyclin H, Cdk5/p35, and (cdc)/cyclin B, with IC50 values of 0.49, 0.16, and 0.65μM, respectively [1-2]. Cell cycle-dependent kinases (CDKs) are key regulators of the cell cycle process [3]. Roscovitine can be used for the treatment of cancer, neurodegenerative diseases, inflammation, viral infections, polycystic kidney disease, and glomerulonephritis [4].
In vitro, Roscovitine (10μM; 24h) treatment significantly upregulated the expression of pro-apoptotic protein BAX in TC-71h and A4573 cells, and downregulated the expression of survivin and XIAP, and induced caspase-dependent cell apoptosis [5]. Roscovitine (10μM; 72h) treatment inhibited the migration and invasion of NRK-52E cells cultured in high glucose conditions and reduced the phosphorylation of ERK1/2 and PPARγ in the cells [6].
In vivo, Roscovitine (50mg/kg/day for 5 days; i.p.) significantly slowed the growth of subcutaneously inoculated A4573 cell xenografts in mice and effectively induced tumor cell apoptosis through a caspase-dependent mechanism [5]. Roscovitine (16.5mg/kg/day for 5 days; i.p.) significantly reduced the tumor growth rate in human papillomavirus (HPV) xenograft mice and increased the survival rate of mice [7].
References:
[1] Meijer, L., Borgne, A., Mulner, O., et al. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem. 243, 527-536 (1997)
[2] Havlícek, L., Hanuš, J., Veselý, J., et al. Cytokinin-derived cyclin-dependent kinase inhibitors: Synthesis and cdc2 inhibitory activity of olomoucine and related compounds. J. Med. Chem. 40, 408-412 (1997).
[3] Bury M, Le Calvé B, Ferbeyre G, et al. New insights into CDK regulators: novel opportunities for cancer therapy[J]. Trends in cell biology, 2021, 31(5): 331-344. [4] Cicenas J, Kalyan K, Sorokinas A, et al. Roscovitine in cancer and other diseases[J]. Annals of translational medicine, 2015, 3(10): 135.
[5] Tirado O M, Mateo-Lozano S, Notario V. Roscovitine is an effective inducer of apoptosis of Ewing's sarcoma family tumor cells in vitro and in vivo[J]. Cancer research, 2005, 65(20): 9320-9327.
[6] Bai X, Hou X, Tian J, Geng J, Li X. CDK5 promotes renal tubulointerstitial fibrosis in diabetic nephropathy via ERK1/2/PPARγ pathway. Oncotarget. 2016;7(24):36510-36528.
[7] Gary C, Hajek M, Biktasova A, Bellinger G, Yarbrough WG, Issaeva N. Selective antitumor activity of roscovitine in head and neck cancer. Oncotarget. 2016;7(25):38598-38611.
Roscovitine (Seliciclib,CYC202)是一种有效的Cdk2/cyclin E抑制剂，IC50值为0.1μM。Roscovitine还抑制Cdk7/cyclin H、Cdk5/p35以及（cdc）/cyclin B，IC50值分别为0.49、0.16和0.65μM [1-2]。细胞周期依赖性激酶（CDKs）是细胞周期进程的关键调节因子 [3]。Roscovitine可用于治疗癌症、神经退行性疾病、炎症、病毒感染、多囊肾病和肾小球肾炎[4]。
在体外，Roscovitine（10μM; 24h）治疗显著上调了TC-71h和A4573细胞中促细胞凋亡蛋白BAX的表达以及下调survivin和XIAP的表达，并且诱导了caspase依赖性细胞凋亡 [5]。Roscovitine（10μM; 72h）处理抑制了高糖培养的NRK-52E细胞的迁移和侵袭，并降低了细胞中ERK1/2和PPARγ的磷酸化 [6]。
在体内，Roscovitine（50mg/kg/day for 5 days; i.p.）显著减慢了皮下接种A4573细胞的小鼠异种移植物的生长，并通过caspase依赖性机制有效诱导肿瘤细胞凋亡 [5]。Roscovitine（16.5mg/kg/day for 5 days; i.p.）显著降低了人乳突类病毒（HPV）异种移植小鼠的肿瘤生长速并增加了小鼠的存活率 [7]。