OTS964 is a potent, orally active compound that operates as a highly selective inhibitor of TOPK with an IC 50 of 28 nM [1]. Additionally, it demonstrates significant inhibitory action against cyclin-dependent kinase CDK11, specifically binding to CDK11B with a K d of 40 nM [2].

OTS964 (10 nM; 48 hours) suppresses cancer cell proliferation [1]. OTS964 (10 nM; 48 hours) increases cancer cell death [1]. OTS964 (0.1-2 μM; 24 and 48 hours) increases the expression of LC3-II and decreases the expression of P62, both in a dose-dependent manner [3]. Cell Proliferation Assay [1] Cell Line: LU-99 cells Concentration: 10 nM Incubation Time: 48 hours Result: Suppressed cancer cell proliferation. Apoptosis Analysis [1] Cell Line: LU-99 cells Concentration: 10 nM Incubation Time: 48 hours Result: Increased cancer cell death. Western Blot Analysis [3] Cell Line: Hs683 cells, H4 cells Concentration: 0.1, 1, 2 μM Incubation Time: 24 and 48 hours Result: Increased the expression of LC3-II and decreased the expression of P62, both in a dose-dependent manner.

OTS964 (intravenously; 40 mg/kg on days 1, 4, 8, 11, 15, and 18) makes tumors shrinking even after the treatment and finally revealing complete regression [1]. OTS964 (oral administration; 50 or 100 mg/kg/day for 2 weeks) achieves complete tumor regression [1]. Animal Model: Nude mice bearing LU-99 lung cancer cells [1] Dosage: 40 mg/kg Administration: Intravenously; on days 1, 4, 8, 11, 15, and 18 Result: The tumors continued shrinking even after the treatment and finally revealed complete regression. Animal Model: Nude mice bearing LU-99 lung cancer cells [1] Dosage: 50 or 100 mg/kg Administration: Oral administration; once every day for 2 weeks Result: Achieved complete tumor regression.