SBE13
目录号 : GC37601
A potent Plk1 inhibitor
Cas No.:775294-82-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | To assay Plk1 kinase activity, cells are lysed after 13?h release in the presence of SBE13 after double thymidine block and kinase is immunoprecipitated from lysates using antibodies. In brief, for each immunoprecipitation 800?μg of total protein are incubated with Plk1 antibody cocktail (1.5?μg) for 2?h at 4°C on a rotator. Immunoprecipitated protein is collected using Protein A/G Agarose beads. Plk1 immunoprecipitates are incubated with casein (1?μg) and with [γ-32P]ATP (1?μCi) for 30?min at 37°C in kinase buffer. Products from the kinase assays are fractionated on 10?% bis-tris-polyacrylamide gels, and phosphorylated substrate is visualized by autoradiography after an exposure of 12-36?h. Equal amounts of immunoprecipitates are subjected to Western blot analysis to confirm equal loading of Plk1 protein in kinase reactions[1]. |
References: [1]. Keppner S, et al. Identification and validation of a potent type II inhibitor of inactive polo-like kinase 1. ChemMedChem. 2009 Nov;4(11):1806-9. | |
SBE 13 is a potent inhibitor of polo-like kinase 1 (Plk1) (IC50 = 0.2 nM) that targets the inactive conformation of the enzyme 1,2. It exhibits no activity against aurora A kinase and less effectively inhibits Plk2 (IC50 > 66 ?M) and Plk3 (IC50 = 875 nM). SBE 13 induces cell cycle arrest, reduces cell proliferation (EC50 = 5-60 ?M), and induces apoptosis in a broad range of human cancer cell lines.2,3
1.Keppner, S., Proschak, E., Schneider, G., et al.Identification and validation of a potent type II inhibitor of inactive polo-like kinase 1Chem. Med. Chem.4(11)1806-1809(2009) 2.Keppner, S., Proschak, E., Kaufmann, M.T., et al.Biological impact of freezing Plk1 in its inactive conformation in cancer cellsCell Cycle9(4)761-773(2010) 3.Keppner, S., Proschak, E., Schneider, A., et al.Fate of primary cells at the G1/S boundary after polo-like kinase 1 inhibition by SBE13Cell Cycle10(4)708-720(2011)
| Cas No. | 775294-82-1 | SDF | |
| Canonical SMILES | COC1=CC=C(CCNCC2=CC=C(OCC3=CC=C(Cl)N=C3)C(OC)=C2)C=C1OC | ||
| 分子式 | C24H27ClN2O4 | 分子量 | 442.94 |
| 溶解度 | Soluble in DMSO | 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 | 2.2576 mL | 11.2882 mL | 22.5764 mL |
| 5 mM | 0.4515 mL | 2.2576 mL | 4.5153 mL |
| 10 mM | 0.2258 mL | 1.1288 mL | 2.2576 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Fate of primary cells at the G₁/S boundary after polo-like kinase 1 inhibition by SBE13
Cell Cycle 2011 Feb 15;10(4):708-20.PMID:21301227DOI:10.4161/cc.10.4.14898.
Human polo-like kinase 1 (Plk1), a key regulator of mitosis, is over-expressed in various human tumors. It is a negative prognostic factor for cancer patients and a measure for the aggressiveness of a tumor. Thus, targeting Plk1 might be a promising approach for cancer therapy. Plk1 inhibitors represent attractive tools for cancer research and for the mechanistic investigation of checkpoint control. Here, we show the impact of Plk1 inhibition on cell cycle regulation in primary cells. After treatment with SBE13 the G₁//S checkpoint was intact, indicated by reduced pRb, resulting in slower cell cycle progression but overall cell proliferation was not significantly impaired. Thus, we provide strong evidence that SBE13 leaves checkpoint control in primary cells unaffected making it a remarkable future anti-cancer therapeutic.
Polo-like kinase 1 inhibitors SBE13 and BI 2536 induce different responses in primary cells
Cell Cycle 2011 Apr 1;10(7):1031-1030.PMID:28927329DOI:10.4161/cc.10.7.15213.
Comment on: Keppner S, et al. Cell Cycle 2011; 10:708-720.
Survival of primary, but not of cancer cells after combined Plk1-HDAC inhibition
Oncotarget 2015 Sep 22;6(28):25801-14.PMID:26317649DOI:10.18632/oncotarget.4445.
In the current study we examined the combination of SAHA and SBE13 in cancer and non-cancer cells. HeLa cells displayed a synergistically reduced cell proliferation, which was much weaker in hTERT-RPE1 or NIH-3T3 cells. Cell cycle distribution differed in HeLa, hTERT-RPE1 and NIH-3T3 cells. SAHA-treated HeLa cells showed slightly increasing cell numbers in G2/M phase, but after combination with SBE13 strongly elevated cell numbers in G2/M and S phase, accompanied by decreasing G0/G1 percentages. hTERT-RPE1 and NIH-3T3 cells showed strongly enriched cell numbers in G0/G1 phase. Western blot and quantitative real time analyses revealed reduced Plk1 mRNA and protein in all cells. p21 protein was strongly induced in cancer, but not in non-cancer cells, corresponding to a different localization in immunofluorescence studies. Additionally, these revealed an abundantly present pRb protein in HeLa cells after any treatment but almost completely vanished pRb staining in treated hTERT-RPE1 cells. These differences could be approved in Western blots against Parp and Caspase 3, which were activated in HeLa, but not in hTERT-RPE1 cells. Thus, we observed for the first time a differential effect of cancer versus non-cancer cells after treatment with SAHA and SBE13, which might be due to the dual role of p21.
Vanillin-derived antiproliferative compounds influence Plk1 activity
Bioorg Med Chem Lett 2014 Nov 1;24(21):5063-9.PMID:25304894DOI:10.1016/j.bmcl.2014.09.015.
We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of human polo-like kinase 1 (Plk1). Some of the new designs were able to inhibit cancer cell proliferation to a similar extent as the lead structure. Two of the compounds ((({4-[(6-chloropyridin-3-yl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine) and (({4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine)) were much stronger in their capacity to reduce HeLa cell proliferation and turned out to potently induce apoptosis and reduce Plk1 kinase activity in vitro.
Combinatorial inhibition of Plk1 and PKCβ in cancer cells with different p53 status
Oncotarget 2014 Apr 30;5(8):2263-75.PMID:24810255DOI:10.18632/oncotarget.1897.
PKCβ and Plk1 are fascinating targets in cancer therapy. Therefore, we combined Enzastaurin targeting PKCβ and SBE13 targeting Plk1 to test synergistic effects in cells with different p53 status. We analyzed cell proliferation and apoptosis induction, and did Western blot and FACScan analyses to examine the combined PKCβ and Plk1 inhibition. p53-wild-type cells are more resistant to the combinatorial treatment than p53-deficient cells, which displayed a synergistic reduction of cell proliferation after the combination. HeLa, MCF-7 and HCT116(p53wt) and HCT116(p53-/-) cells differed in their cell cycle distribution after combinatorial treatment in dependence on a functional p53-dependent G1/S checkpoint (p53-deficient cells showed an enrichment in S and G2/M, p53-wild-type cells in G0/G1 phase). hTERT-RPE1 cells did not show the synergistic effects of cancer cells. Thus, we demonstrate for the first time that Plk1 inhibition using SBE13 enhances the effects of Enzastaurin in cancer cells. HCT116(p53wt) and HCT116(p53-/-) cells confirmed the p53-dependence of different effects after Plk1 and PKCβ inhibition observed in HeLa and MCF-7 cells. Obviously, p53 protects cells from the cytotoxicity of Enzastaurin in combination with SBE13. For that reason this combination can be useful to treat p53-deficient cancers, without displaying toxicity to normal cells, which all have functional p53.