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 & Target: IC50: 26.9?μM (mitotic Polo-like kinase (PLK))
Kd: 26.9?μM (protein-protein interaction via the Polo-box domain (PBD))^[1] In Vitro: 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].