Poloxin-2 is a potent and selective Plk1 PBD inhibitor with anti-tumour activity that reduces the protein level of Plk1 in HeLa cells.

NPCs:1 μM

Poloxin-2 increases neurite differentiation of rat NPCs in a dose-dependent manner (EC50=~1 μM) in adherent culture.
Under neural sphere-forming conditions, Poloxin-2 (1.5-5 μM) induces neuronal formation in secondary neurospheres derived from adult rat hippocampus and subventricular zone (SVZ) (40-60% TuJ1+ cells).Furthermore, hippocampal NPCs treated with Poloxin-2and cultured on microelectrode arrays for 12 days exhibit neuronal morphology and spontaneous spike activity, indicating the presence of functional, mature neurons[2].In comparison to cells treated with the carrier (dimethyl sulfoxide, DMSO),Poloxin-2 significantly attenuates the growth of tumor cells.TACC3 is a known target of Poloxin-2 in rodent neural progenitor cells. Poloxin-2 has been shown to induce instability in cells expressing TACC3, leading to a gradual reduction in endogenous TACC3 protein levels over time[1].

In tumors treated with Poloxin-2, there is a significant reduction in tumor cell proliferation (approximately two-fold decrease). Compared to tumors treated with the carrier control, Poloxin-2-treated tumors show signs of increased cell death (reduced cell structures/increased condensation).
Poloxin-2treatment markedly reduces the expansion of frontal-to-tail tumor growth and corpus callosum invasion in waveform protein-positive GBM1 cells. It was also observed that the survival rate of animals carrying GBMX1 tumors (established 2 or 6 weeks prior to treatment) significantly increases with the 10-week Poloxin-2treatment regimen. No mouse had to be removed from the study due to adverse effects of the treatment. Another experiment using continuous Poloxin-2 treatment until the endpoint also shows a significant increase in the survival rate of animals carrying GBMX1 tumors. Histopathological endpoint analysis of animals treated with Poloxin-2 and the vehicle confirms a significant reduction in tumor size in Poloxin-2-treated mice[1].