OTS514

OTS514 is an inhibitor of lymphokine-activated killer T cell-originated protein kinase (TOPK; IC₅₀ = 2.6 nM), a serine-threonine kinase often overexpressed and transactivated in several types of cancer.^1,2 OTS514 (10 nM) selectively inhibits growth of patient-derived acute myeloid leukemia (AML) cells over normal CD34⁺ cells. It shows similar growth inhibitory effects in multiple small cell lung, kidney, and ovarian cancer cell lines (IC₅₀s = 0.4-42.6 nM).^3,4,5 In vivo, OTS514 (25 and 50 mg/kg) increases survival in a peritoneal mouse dissemination model of ovarian cancer. It also dose-dependently inhibits tumor growth in an A549 mouse xenograft model when administered at doses of 1, 2.5, and 5 mg/kg.¹

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1. Matsuo, Y., Park, J.H., Miyamoto, T., et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci. Transl. Med. 6(259), 259ra145 (2014).

2. Alachkar, H., Mutonga, M., Malnassy, G., et al. T-LAK cell-originated protein kinase presents a novel therapeutic target in FLT3-ITD mutated acute myeloid leukemia. Oncotarget 6(32), 33410-33425 (2015).

3. Kato, T., Inoue, H., Imoto, S., et al. Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells. Oncotarget 7(14), 17652-17664 (2016).

4. Park, J.-H., Inoue, H., Kato, T., et al. TOPK (T-LAK cell-originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer. Cancer Sci. 108(3), 488-496 (2017).

5. Ikeda, Y., Park, J.H., Miyamoto, T., et al. T-LAK cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in ovarian cancer. Clin. Cancer. Res 22(24), 6110-6117 (2016).