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Ro 3306

现货
Catalog No.
A8885
CDK1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 750.00
现货
10mg
¥ 900.00
现货
50mg
¥ 2,800.00
现货

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Background

RO-3306 is an ATP-competitive, potent cyclin-dependent kinase (CDK) 1 inhibitor with Ki values of 35 and 110 nM for cdk1/cyclin B1 and cdk1/cyclin A, respectively.
Cell cycle progression is regulated by a series of CDKs. Cdk1 controls the cell cycle entry into mitosis. It forms a bipartite complex with cyclin B and phosphorylates a spectrum of substrates that coordinate nuclear envelope breakdown, chromosome condensation, assembly of the mitotic spindle and activation of the spindle assembly checkpoint.  
CDK1 inhibitor RO-3306 was reported to impair BRCA1 localization to DSBs, and consistent with this, suppressed RAD51 focus formation in DU145 cells when applied at the GI50 (1μM).  Co-treatment of 100 nM AZ12253801 and 1 μM RO-3306 manifested a marked increase in pre-G1
DNA, indicating apoptosis induction. In viability assays, RO-3306 induced a significant shift to the left of the AZ12253801 dose-response curve, with 2.4-fold reduction in GI50, comparable to RAD51 depletion or inhibition. At sub-50nM AZ12253801 concentrations there was more striking sensitization, with 13-fold reduction in GI80. Paralleling effects of RAD51 knockdown, RO-3306 did not affect AZ12253801 sensitivity of PC3 or LNCaP cells, but did sensitize 22Rv1 cells.
References:
[1]. Lodhia KA, Gao S, Aleksic T, et al. Suppression of homologous recombination sensitizes human tumor cells to IGF-1R inhibition. Int J Cancer. 2014 Nov 12.

文献引用

1. Liu JC, Granieri L, et al. "Identification of CDC25 as a Common Therapeutic Target for Triple-Negative Breast Cancer." Cell Rep. 2018 Apr 3;23(1):112-126. PMID:29617654
2. Özer Ö, Bhowmick R, et al. "Human cancer cells utilize mitotic DNA synthesis to resist replication stress at telomeres regardless of their telomere maintenance mechanism." Oncotarget. 2018 Mar 23;9(22):15836-15846. PMID:29662610
3. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID:29507054
4. Arpita Mukherjee, Upayan Patra, et al. "Rotaviral non‐structural protein 4 triggers Dynamin related protein 1‐dependent mitochondrial fragmentation during infection." CELLULAR MICROBIOLOGY.2018.February 28.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt351.45
Cas No.872573-93-8
FormulaC18H13N3OS2
Solubility≥4.39mg/mL in DMSO
Chemical Name(Z)-5-(quinolin-6-ylmethylene)-2-((thiophen-2-ylmethyl)amino)thiazol-4(5H)-one
SDFDownload SDF
Canonical SMILESO=C1N=C(NCC2=CC=CS2)S/C1=C\C3=CC=C(N=CC=C4)C4=C3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

结合实验

使用从Hi5昆虫细胞表达和分离的重组人CDK1/cyclin B1、CDK1/cyclin A、CDK2/cyclin E和CDK4/cyclin D进行CDK活性测定。使用均匀时间分辨荧光测定法在96孔板中进行测定。测定缓冲液含有25 mM Hepes、6.25 mM MgCl2、0.003%TWEEN 20、0.3 mg/ml BSA、1.5mM DTT和ATP,包含162 μM(CDK1)、90 μM(CDK2)或135 μM(CDK4)。CDK1和CDK2缓冲液含有10 mM MgCl2。将测试化合物在测定缓冲液中稀释至20 μl,稀释为最终浓度的3倍,并通过加入含有pRB底物(0.185 μM)的40 μl测定缓冲液起始反应。将板在37℃下恒温搅拌孵育30分钟,通过在25 mM Hepes/24mM EDTA/0.2mg/ml BSA中加入15 μl 1.6 μM抗磷酸化pRB抗体终止反应。在振荡温育30分钟后,加入15 μl 的在25 mM Hepes/0.5 mg/ml BSA中含有3nM Lance-Eu-W1024标记的抗兔IgG和60 nM紫杉蓝蛋白缀合的抗His-6抗体,孵育1小时。使用Victor-V多标签阅读器,激发光为340nm,发射光615nm和665nm读板。从665nm处的读数计算IC50值,并对615nm处的铕读数进行归一化。

细胞实验 [1]:

细胞系

增殖人细胞HCT116、SW480、Hela

溶解方法

该化合物在DMSO中的溶解度大于4.4 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

9 μM,20 h,

应用

在增殖的人类癌细胞HCT116、SW480和HeLa中,用RO-3306处理20小时完全阻断G2/M期的细胞周期。在癌细胞系RKO、SJSA、MDAMB-435和DU145中,RO-3306为晚期G2期的细胞同步提供了有效的手段。在HeLa细胞中,使用9 μM RO-3306阻断18小时后,停止使用RO-3306,HeLa细胞富集在有丝分裂期,随后在不存在或存在9 μM RO-3306的情况下发生了形态学变化。4 μM RO-3306处理48小时诱导癌细胞凋亡。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Vassilev L T, Tovar C, Chen S, et al. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1[J]. Proceedings of the National Academy of Sciences, 2006, 103(28): 10660-10665.

质量控制

化学结构

Ro 3306

相关生物数据

Ro 3306

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Ro 3306

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Ro 3306