GW843682X

GW843682X is a reversible, cell-permeable polo-like kinase (PLK) inhibitor.¹ It selectively inhibits Plk1 and Plk3 (IC₅₀s = 2.2 and 9.1 nM, respectively) over PDGFR1β, VEGFR2, Aurora A, and Cdk2/cyclin A (IC₅₀s = 160, 360, 4,800, and 7,600 nM, respectively), as well as over 30 other kinases, in a cell-free assay. GW843682X also inhibits Plk1 activity in vitro in HeLa cells (IC₅₀ = 0.14 μM in a reporter assay using chimeric Plk1). It inhibits growth in nine cancer cell lines in a panel (IC₅₀s = 0.11-0.7 μM) but not of PC3 human prostate cancer cells (IC₅₀ = 6.82 µM) or non-cancerous human diploid fibroblasts (HDFs; IC₅₀ = 6.14 μM). GW843682X inhibits growth of MES-SA human uterine sarcoma cells, as well as of the drug-resistant, P-glycoprotein-expressing MES-SA/Dx5 subline (IC₅₀s = 0.21 and 0.21 μM, respectively). It also inhibits the growth of patient-derived leukemia cells (IC₅₀s = <0.25-0.8 μM).² GW843682X induces G₂/M cell cycle arrest and apoptosis of H460 human lung and PALL-2 and MOLM13 human leukemia cancer cells in a concentration-dependent manner.^1,2

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1. Lansing, T.J., McConnell, R.T., Duckett, D.R., et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol. Cancer Ther. 6(2), 450-459 (2007).

2. Ikezoe, T., Yang, J., Nishioka, C., et al. A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies. Leukemia 23(9), 1564-1574 (2009).