GSK461364

GSK461364 is a potent, reversible inhibitor of Plk1 (K_i = 2.2 nM).¹ It is less effective against Plk2 and Plk3 (K_is = 860 and 1,000 nM, respectively) and at least 1,000-fold selective for Plk1 over a panel of 48 other kinases.¹ GSK461364 dose-dependently halts cell cycling in diverse proliferating cancer cell lines and, at higher doses, triggers apoptosis.¹ It appears to be more effective against p53-deficient tumors and is able to cross the blood-brain barrier.^2,3 GSK461364 is effective in vivo, inducing tumor growth inhibition or growth delay in xenograft models in mice.^4,1

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1. Gilmartin, A.G., Bleam, M.R., Richter, M.C., et al. Distinct concentration-dependent effects of the polo-like kinase 1-specific inhibitor GSK461364A, including differential effect on apoptosis. Cancer Res. 69(17), 6969-6977 (2009).

2. Degenhardt, Y., Greshock, J., Laquerre, S., et al. Sensitivity of cancer cells to Plk1 inhibitor GSK461364A is associated with loss of p53 function and chromosome instability. Mol. Cancer Ther. 9(7), 2079-2089 (2010).

3. Danovi, D., Folarin, A., Gogolok, S., et al. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One 8(10), 1-13 (2013).

4. Schöffski, P. Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist 14(6), 559-570 (2009).