TAK-960 (dihydrochloride)

TAK-960 dihydrochloride is an orally available, selective inhibitor of polo-like kinase 1 (PLK1), with an IC₅₀ of 0.8 nM. TAK-960 dihydrochloride also shows inhibitory activities against PLK2 and PLK3, with IC₅₀s of 16.9 and 50.2 nM, respectively. TAK-960 dihydrochloride inhibits proliferation of multiple cancer cell lines and exhibits significant efficacy against multiple tumor xenografts^[1]. IC50 & Target: IC50: 0.8 nM (PLK1, + ATP), 16.9 nM (PLK2, + ATP), 50.2 nM (PLK3, + ATP)^[1] In Vitro: TAK-960 dihydrochloride treatment causes accumulation of G2-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3). TAK-960 dihydrochloride (2-1000 nM; 72 hours) inhibits proliferation of multiple cancer cell lines, with mean EC₅₀ values ranging from 8.4 to 46.9 nM, but not in nondividing normal cells^[1].
TAK-960 dihydrochloride (8?nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells^[2]. In Vivo: TAK-960 dihydrochloride exhibits (10 mg/kg; p.o.; once daily for 2 weeks) significant efficacy against multiple tumor xenografts^[1].
In animal models, TAK-960 dihydrochloride (p.o.) increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts^[1].