Poloppin II

Poloppin II is an orally active PBD inhibitor that blocks the binding of phosphopeptide substrates to PLK1/PLK2 PBD, with IC₅₀ values of 41 µM and 105 µM for human PLK1/PLK2 PBD, respectively. Poloppin II binds to PLK4 PBD to inhibit PLK4-dependent mitotic functions. Poloppin II can be used in research on kras-mutant colorectal cancer^[1]. In Vitro:Poloppin II (16 h) induces mitotic arrest in HeLa cells with EC₅₀ 61 nM (MI EC₅₀ 0.069 μM; 81% max)^[1].
Poloppin II (1 h at 22°C) inhibits phosphopeptide binding to PLK1 PBD with IC₅₀ 41 μM and to PLK2 PBD with IC₅₀ 105 μM in FP assays^[1].
Poloppin II (100 μM; 1 h at 37°C; 3 min over 42-66°C gradient) engages PLK1 and PLK4 in NanoLuc thermal shift assays in HeLa cells^[1].
Poloppin II is inactive against hERG and stable in human and mouse hepatocytes^[1]. In Vivo:Poloppin-II (50-200 mg/kg; p.o.; once every three days) is effective against mutant KRAS-expressing HCT116 colorectal cancer xenografts in athymic nude mice, reducing tumour growth and increasing phospho-Ser10 histone H3 in tumours^[1].