GW843682X

GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC₅₀s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ～30 other kinases. IC50 & Target: IC50: 2.2 nM (PLK1), 9.1 nM (PLK3)^[1] In Vitro: GW843682X (compound 1) is effective on inhibition of growth of tumor cells, with IC₅₀s of 0.41, 0.57, 0.11, 0.38, and 0.70 μM for A549, BT474, HeLa, H460 and HCT116 cell lines. GW843682X dose-dependently inhibits PLK1 phosphorylation of Ser15-p53, with an IC₅₀ of 0.14 μM. GW843682X (3 μM) causes a strong G2-M arres in HDF cells and H460 cells after treatment for 24, 48, and 72 h. GW843682X (5 μM) leads to apoptosis in H460 cells instead of HDF cells^[1]. GW843682X inhibits proliferation of U937 cells with an EC₅₀ of 120 nM. GW843682X (500 nM) in combination with 5 μM VP-16 suppresses 50% of entry into mitosis in U937 cells^[2]. GW843682X (0.06-1?μM) has inhibitory activities against proliferation of acute leukemia cells, and potentiates the anti-proliferative activity of vincristine. Moreover, GW843682X (0.1-1?μM) induces apoptosis of leukemia cells in a dose- and time-dependent manner. GW843682X (0.5-1?μM) dephosphorylates Bcl-xl in leukemia cells^[3].