GSK-461364

A potent, selective, and reversible ATP-competitive PLK1 inhibitor with Ki of 2.2 nM; >390-fold greater selectivity for Plk1 than for Plk2 and Plk3 and 1,000-fold greater selectivity than for a panel of 48 other kinases; shows antiproliferative activity against >120 tumor cell lines and potently inhibits the proliferation with IC50s of 20 nM) blocks cells in G2-M phase with reduction of cells in G1 phase of A549 lung carcinoma line. GSK461364 (10-250 nM) blocks cells in G2 and M phases of the cell cycle and causes M-phase caspase-3/caspase-7 activation in cancer cells. GSK461364 (0.5-2 μM) decreases level of PLK1 and pCDC25C, and cuases a dose- and time-dependent increase in pHisH3, an indicator of mitotic arrest in OS cell lines. (In Vivo) :GSK461364 (50 mg/kg) exhibits various degrees of tumor growth delay (TGD) in multiple xenograft tumor models by i.p. one dose every 2 days repeated twelve times (q2dx12) .