| CAS |
No.1062243-51-9 |
| 英文名称 |
Ro3280 |
| 分子式 |
C27H35F2N7O3 |
| 分子量 |
543.61 |
| 溶解性 |
Soluble in DMSO ≥3mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
Off-white to yellow Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 靶点 |
Polo-like Kinase (PLK) |
| 通路 |
Cell Cycle |
| 背景说明 |
Ro3280 是一种有效的，高度选择性的 PLK1 抑制剂。 |
| 生物活性 |
Ro3280 is a potent， highly selective inhibitor of PLK1 with an IC50 and a Kd of 3 nM and 0.09 nM， respectively， and nearly has no effect on PLK2 and PLK3.[1-3] |
| In Vitro |
Ro3280 (RO3280) 抑制 NB4 和 K562 细胞中的 PLK1 活性，IC50 分别为 13.45 nM 和 301 nM。RO3280 对 6 种白血病细胞的生长具有抑制活性，对 U937、HL60、NB4、K562、分别为 MV4-11 和 CCRF 细胞系。RO3280 还抑制原代 ALL 和 AML 细胞的生长，IC50 分别为 35.49-110.76 nM 和 52.80-147.50 nM。RO3280 (50 或 100 nM) 诱导急性白血病细胞凋亡和细胞周期紊乱[1]。Ro3280 在 H82、H69、A549 肺癌细胞系中表现出强大的活性，EC50 分别为 6 nM、7 nM 和 82 nM。Ro3280 还抑制其他几种癌细胞系，浓度较低[2]。RO3280 对 5637 和 T24 人膀胱癌细胞具有细胞毒性，IC50 约为 100 nM。 |
| In Vivo |
Ro3280 (RO3280，40 mg/kg，iv) 在植入 HT-29 结直肠癌细胞的小鼠异种移植模型中抑制 72% 的肿瘤生长，并且当更频繁地给药时，RO3280 完全抑制肿瘤生长[2]。RO3280 (30 mg/kg，每 5 天一次，ip) 在裸鼠模型中显示出显著的抗膀胱癌活性[3]。 |
| 细胞实验 |
Leukemia cells or primary leukemia cells (2 × 104) are seeded in 96-well plates overnight and incubated with DMSO， or increasing concentrations of RO3280 (0.05-120 μM) for 24 h. The same volume of DMSO added to the vehicle treated wells. Each drug concentration is replicated four times. Then， 10 μL CCK8 solution is added to each well， incubated at 37°C for 2-4 h and the optical density (OD) values are measured at 450 nm using a scanning multi-well spectrophotometer. Relative survival rate is calculated from the absorbance values compared with the control group. The proliferation of cells is calculated as a percentage of the DMSO-treated control wells with 50% inhibitory concentration (IC50) values derived after plotting proliferation values on a logarithmic curve. The IC50 of PLK1 inhibitor is calculated by Graph Prism software[1]. |
| 动物实验 |
Briefly， mice (female， 4-5 weeks of age) are used in the assay. Cells (5 × 106 cells in 150 μL) are suspended in RPMI 1640 and injected subcutaneously into the flank of each BALB/c nude mouse. On day 5， tumour size is measured， the animals are randomized into two groups (n = 15 per group)， and RO3280 (40 mg/kg， once every 5 days) treatment is initiated by intraperitoneal injection. The control group is treated with vehicle (1.5% DMSO in PBS). The drug (or vehicle) treatment is performed for 40 days. The length and width of the resulting tumours (in millimetres) are measured every 3 days with callipers. The tumour diameter is measured， and the volume (length × width2 × 0.52) is calculated. The mice are humanely killed on day 45， and the tumours are dissected and weighed. Western blot and immunohistochemistry assays are also performed with these sections. Then， the tumours are fixed， embedded and cut into 3‐μm‐thick sections， which are subsequently stained with haematoxylin and eosin to permit the observation of the tumour margin[3]. |
| 数据来源文献 |
[1]. Wang NN， et al. Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280， a novel PLK1 inhibitor， induces apoptosis in leukemia cells. Int J Mol Sci. 2015 Jan 7;16(1):1266-92.
[2]. Chen S， et al. Identification of novel， potent and selective inhibitors of Polo-like kinase 1. Bioorg Med Chem Lett. 2012 Jan 15;22(2):1247-50.
[3]. Zhang Z， et al. Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor induces mitotic catastrophe and apoptosis in human bladder cancer cells. J Cell Mol Med. 2017 Apr;21(4):758-767. |
| 规格 |
1mg 2mg 5mg 10mg 25mg |
| 单位 |
瓶 |
中文
英语
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