TAK-960 monohydrochloride is an orally available compound that selectively inhibits polo-like kinase 1 (PLK1) with an IC 50 of 0.8 nM. It also demonstrates inhibitory activity against PLK2 (IC 50 of 16.9 nM) and PLK3 (IC 50 of 50.2 nM). Moreover, TAK-960 monohydrochloride effectively suppresses the proliferation of various cancer cell lines and exhibits significant efficacy against multiple tumor xenografts.

TAK-960 monohydrochloride treatment causes accumulation of G2-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3). TAK-960 monohydrochloride (2-1000 nM; 72 hours) inhibits proliferation of multiple cancer cell lines, with mean EC 50 values ranging from 8.4 to 46.9 nM, but not in nondividing normal cells[1]. TAK-960 monohydrochloride (8?nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells[2]. Cell Viability Assay[1]Cell Line: HT-29, HCT116, COLO320DM, HCT-15, RKO, SW480, K-562….Hela, DU 145 cells Concentration: 2-1000 nM Incubation Time: 72 hours Result: Inhibited proliferation of human cancer cell lines regardless of TP53 and KRAS mutation and MDR1 expression status.

TAK-960 monohydrochloride exhibits (10 mg/kg; p.o.; once daily for 2 weeks) significant efficacy against multiple tumor xenografts[1]. In animal models, TAK-960 monohydrochloride (p.o.) increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts[1]. Animal Model: nude mice or SCID mice (bearing HCT116, PC-3, BT474, A549, NCI-H1299, NCI-H1975, A2780, and MV4-11 cells)[1]Dosage: 10 mg/kg Administration: P.o.; once daily for 2 weeks Result: Substantial antitumor activity and good tolerability.