Poloppin
目录号 : GC60294
Poloppin是一种有效的细胞渗透抑制剂，可抑制有丝分裂的polo样激酶(PLK)IC50=26.9μM)，并可通过Polo-box结构域(PBD)阻止蛋白之间的相互作用(Kd=29.5μM)。Poloppin选择性地杀死表达突变KRAS的细胞，增强有丝分裂中的死亡。Poloppin可用作KRAS突变型癌症的研究，可作为单一试剂，或与c-MET抑制剂联合使用。
Cas No.:683808-78-8
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
Poloppin is a potent, cell penetrant inhibitor of the mitotic Polo-like kinase (PLK) (IC50=26.9 μM) and prevents the protein-protein interaction via the Polo-box domain (PBD) (Kd= 29.5 μM). Poloppin selectively kills cells expressing mutant KRAS, enhancing death in mitosis. Poloppin is used for the study of KRAS-mutant cancers as single agents, or in combination with c-MET inhibitors[1].
Poloppin (0-200 μM) competitively inhibits the binding of a TAMRA-labeled substrate peptide to the PLK1 PBD, exhibiting an IC50 value of 26.9 μM in an FP assay; the isothermal titration calorimetry of Poloppin binding to the PBD domain of PLK1 with a Kd of 29.5 μM[1].Poloppin (0-100 μM) triggers a dose-dependent mitotic arrest and induces multiple anomalies in mitosis in cells, the EC50 value is 29.9 μM. In representative images of U2OS cells with 12.5 μM Poloppin, <5% of cells exhibit normal metaphase chromosome alignment, and shows bipolar or disordered spindles and non-congressed chromosomes in cells[1].Poloppin (0-200 μM; 24 hours) inhibits SW48 isogenic parental or KRAS G12D cells growth with GI50 values of 13.7 μM and 5.3 μM, respectively. It inhibits KRAS wild-type p53 and KRAS MUT p53 MEFs cells with GI50 values of 51.1 and 49.5 μM, respectively. When the medium is added 500nM 4-OH Tamoxifen to the culture media overnight, Poloppin inhibits KRAS wild-type p53 and KRAS MUT p53 MEFs cells with GI50 values of 43.7 μM and 17.6 μM, respectively[1].Poloppin (0-10 μM; 72 hours) sensitizes mutant KRAS-expressing cells to inhibitors of the c-MET tyrosine kinase. SW48 cell bearing mutant KRAS are sensitized to Poloppin after inhibition of c-MET, the GI50 values of Poloppin combination with Crizotinb are 0.23 uM and 0.08 uM, respectively in SW48 KRAS WT and KRAS G12D cells. In the contrast, the GI50 values are 0.56 uM and 0.63 uM in SW48 KRAS WT or KRAS MUT cells when treated with Crizotinib alone[1]. Cell Viability Assay[1] Cell Line: SW48 isogenic parental or KRAS G12D cells
[1]. Ana J Narvaez, et al. Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS. Cell Chem Biol. 2017 Aug 17;24(8):1017-1028.e7.
| Cas No. | 683808-78-8 | SDF | |
| Canonical SMILES | O=C(O)CCC1=CC=C(C2=CC=C(Br)C=C2)N1C3=CC=CC=C3C(F)(F)F | ||
| 分子式 | C20H15BrF3NO2 | 分子量 | 438.24 |
| 溶解度 | 储存条件 | ||
| 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 | 2.2819 mL | 11.4093 mL | 22.8185 mL |
| 5 mM | 0.4564 mL | 2.2819 mL | 4.5637 mL |
| 10 mM | 0.2282 mL | 1.1409 mL | 2.2819 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。
Modulating Protein-Protein Interactions of the Mitotic Polo-like Kinases to Target Mutant KRAS
Cell Chem Biol 2017 Aug 17;24(8):1017-1028.e7.PMID:28807782DOI:PMC5563081
Mutations activating KRAS underlie many forms of cancer, but are refractory to therapeutic targeting. Here, we develop Poloppin, an inhibitor of protein-protein interactions via the Polo-box domain (PBD) of the mitotic Polo-like kinases (PLKs), in monotherapeutic and combination strategies to target mutant KRAS. Poloppin engages its targets in biochemical and cellular assays, triggering mitotic arrest with defective chromosome congression. Poloppin kills cells expressing mutant KRAS, selectively enhancing death in mitosis. PLK1 or PLK4 depletion recapitulates these cellular effects, as does PBD overexpression, corroborating Poloppin's mechanism of action. An optimized analog with favorable pharmacokinetics, Poloppin-II, is effective against KRAS-expressing cancer xenografts. Poloppin resistance develops less readily than to an ATP-competitive PLK1 inhibitor; moreover, cross-sensitivity persists. Poloppin sensitizes mutant KRAS-expressing cells to clinical inhibitors of c-MET, opening opportunities for combination therapy. Our findings exemplify the utility of small molecules modulating the protein-protein interactions of PLKs to therapeutically target mutant KRAS-expressing cancers.