GSK-1070916

942918-07-2

C30H33N7O

DMSO : >= 26.5 mg/mL (52.20 mM)

Cell Cycle/DNA Damage; Epigenetics

GSK-1070916 is a potent and selective ATP-competitive inhibitor of aurora B and aurora C with K_is of 0.38 and 1.5 nM, respectively, and is >250- fold selective over Aurora A. IC50 & Target: Ki: 0.38 nM (Aurora B), 1.5 nM (Aurora C)^[1] In Vitro: GSK-1070916 potently inhibits Aurora B/INCENP and Aurora C/INCENP kinases with K_is of 0.38+/-0.29 and 1.45+/-0.35 nM, respectively, but is less potent against Aurora A/ TPX2 with a K_i of 492+/-61 nM. GSK-1070916 also inhibits FLT1, TIE2, SIK, FLT4, and FGFR1 with IC₅₀ values of 42, 59, 70, 74, and 78 nM, respectively. Treatment of A549 human lung cancer cells with GSK-1070916 results in a potent antiproliferative effect (EC₅₀=7 nM)^[1]. GSK-1070916 inhibits a panel of tumor cell lines and is shown o inhibits the phosphorylation of HH3- S10 in all cell lines with average EC₅₀ values ranging from 8 to 118 nM^[2]. In Vivo: In nude mice implanted with human colon tumor (HCT116) xenografts, a single dose of GSK-1070916 administered i.p. inhibits HH3-S10 phosphorylation in a dose-dependent manner. Repeated i.p. administration of GSK-1070916 produces complete or partial antitumor activity in 4 of 8 tumor types [lung, A549; colon, HCT116; acute myelogenous leukemia (AML), HL60; and chronic myelogenous leukemia, K562], stable disease in 3 of 8 (colon, Colo205; lung, H460; and breast, MCF-7), and tumor growth delay in 1 of 8 tumor types (colon, SW620). Daily administration of GSK-1070916 is generally well-tolerated^[2].