Biochem/physiol Actions

GSK461364 is an imidazotriazine derivate that inhibits polo-like kinase 1 (Plk1) in a potent, reversible, ATP-competitive, and highly selective manner (Kiapp ﹤0.5 nM vs. 0.86 µM for Plk2 and 200 µM for Plk3; ATP Kmapp = 16 µM), exhibiting much reduced or little potency toward a panel of 262 kinases. GSK461364A inhibits the growth of various cancer cultures (IG50 ﹤100 nM) as a result of either growth arrest (cytostasis) or cytotoxicity in vitro and effectively suppresses the expansion of various human tumor exnografts in mice in vivo (25 or 50 mg/kg i.p. q2dx12).