Roscovitine (Seliciclib,CYC202)
(Synonyms: 细胞周期蛋白B激酶抑制剂,Roscovitine; CYC202; R-roscovitine) 目录号 : GC11401
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。
Cas No.:186692-46-6
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | TC-71 and A4573 cells |
Preparation Method | Cultures of TC-71 and A4573 cells were established by plating either 2×104 cells per well in 96-well tissue culture plates (for caspase activity determinations) or 2×105 cells per well in six-well plates (for apoptosis assays). After overnight incubation, cells were treated for 24 hours with either 10μM Roscovitine, 5μg/mL cisplatin (as a positive inducer of caspase-3–dependent apoptosis), or DMSO vehicle (as the negative control), each in the presence or absence of the Ac-DEVD-CHO caspase-3/7 inhibitor at a 20μM final concentration. All treatments were done in triplicate. Following treatment, the extent of apoptosis induction was determined as described above, and caspase-3/7 activity determinations were carried out using the Apo-ONE Homogeneous Caspase-3/7 Assay following the manufacturer's protocol. At the same time, protein blotting analysis was carried out. |
Reaction Conditions | 10μM; 24h |
Applications | Roscovitine treatment significantly upregulated the expression of pro-apoptotic protein BAX, as well as downregulated the expressions of survivin and XIAP, and induced caspase-dependent cell apoptosis. |
| Animal experiment [1]: | |
Animal models | Male athymic nude mice injected with A4573 cells |
Preparation Method | Mice were inoculated s.c. into the right posterior flank with 4×106 A4573 cells in 100μL of Matrigel basement membrane matrix. Xenografts were grown to a mean tumor volume of 129±30mm3. Roscovitine was first dissolved in either absolute methanol or DMSO. A carrier solution was produced by using a diluent containing 10% Tween 80, 20% N-N-dimethylacetamide, and 70% polyethylene glycol 400. Mice were randomized into two groups (six animals per group) and treatment was initiated. One group was treated with Roscovitine, administered as a single daily i.p. injection, at a dose of 50mg/kg, for either 5 days or two 5-day series with a 2-day break in between. The control group received i.p. injections of the carrier solution following identical schedules. All mice were sacrificed by asphyxiation with CO2. Roscovitine-treated mice were euthanized either 7 days after the first injection or up to 4 weeks after completion of the treatment. At those times, tumors were removed, measured, and prepared for TUNEL assays. |
Dosage form | 50mg/kg/day for either 5 days or two 5-day series with a 2-day break in between; i.p. |
Applications | Roscovitine significantly slowed down the growth of subcutaneous inoculated A4573 cell xenografts in mice, and effectively induced tumor cell apoptosis through a caspase-dependent mechanism. |
References: | |
| Cas No. | 186692-46-6 | SDF | |
| 别名 | 细胞周期蛋白B激酶抑制剂,Roscovitine; CYC202; R-roscovitine | ||
| 化学名 | (2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol | ||
| Canonical SMILES | CCC(CO)NC1=NC2=C(C(=N1)NCC3=CC=CC=C3)N=CN2C(C)C | ||
| 分子式 | C19H26N6O | 分子量 | 354.45 |
| 溶解度 | DMSO:71 mg/mL (200.31 mM);Ethanol:71 mg/mL (200.31 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8213 mL | 14.1064 mL | 28.2127 mL |
| 5 mM | 0.5643 mL | 2.8213 mL | 5.6425 mL |
| 10 mM | 0.2821 mL | 1.4106 mL | 2.8213 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.50%
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