Poloppin 

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) (K_d= 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].

IC50: 26.9 μM (mitotic Polo-like kinase (PLK))
Kd: 26.9 μM (protein-protein interaction via the Polo-box domain (PBD))^[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 K_d 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 (HY-50878) 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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

438.24

C₂₀H₁₅BrF₃NO₂

683808-78-8

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• [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.  [Content Brief]