TAK-960 monohydrochloride is an orally available compound that selectively inhibits polo-like kinase 1 (PLK1) with an IC₅₀ of 0.8 nM. It also demonstrates inhibitory activity against PLK2 (IC₅₀ of 16.9 nM) and PLK3 (IC₅₀ of 50.2 nM), and effectively suppresses the proliferation of various cancer cell lines, exhibiting significant efficacy against multiple tumor xenografts.

Treatment with TAK-960 monohydrochloride induces G2-M cell accumulation, abnormal polo-like kinase mitosis morphology, and elevates histone H3 phosphorylation (pHH3). At concentrations ranging from 2-1000 nM over 72 hours, TAK-960 monohydrochloride effectively suppresses the proliferation of a broad spectrum of cancer cell lines, exhibiting mean EC 50 values between 8.4 and 46.9 nM, while sparing nondividing normal cells[1]. Specifically, an 8 nM concentration of TAK-960 monohydrochloride results in G2/M cell cycle arrest, demonstrating minimal cytotoxicity in HeLa cells[2]. This inhibition includes cells regardless of TP53 and KRAS mutation status, as well as MDR1 expression, highlighting its potential broad applicability in cancer treatment.

TAK-960 monohydrochloride, administered orally at a dosage of 10 mg/kg once daily for two weeks, has demonstrated significant efficacy in treating multiple tumor xenografts, including those in nude or SCID mice implanted with a variety of cancer cells such as HCT116, PC-3, BT474, A549, NCI-H1299, NCI-H1975, A2780, and MV4-11. This compound notably increases pHH3 levels in a dose-dependent manner and has shown considerable effectiveness in inhibiting the growth of HT-29 colorectal cancer xenografts, exhibiting both substantial antitumor activity and good tolerability in these models.