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].

TOPK:28 nM, CDK11B:40 nM (Kd)

OTS964 treatment at a concentration of 10 nM for 48 hours has been shown to effectively suppress the proliferation of cancer cells and increase cancer cell death in LU-99 cells, as reported in study [1]. Moreover, when OTS964 is administered to Hs683 and H4 cells at varying concentrations (0.1, 1, and 2 μM) for 24 and 48 hours, it significantly upregulates the expression of LC3-II and downregulates P62 expression in a dose-dependent manner, as demonstrated in study [3]. This indicates OTS964's strong potential in inducing autophagy and promoting apoptotic processes in cancer cells.

OTS964, administered intravenously at a dosage of 40 mg/kg on days 1, 4, 8, 11, 15, and 18, leads to continuous tumor shrinkage post-treatment, culminating in complete regression in nude mice bearing LU-99 lung cancer cells [1]. Similarly, oral administration of OTS964 at daily doses of 50 or 100 mg/kg for two weeks results in complete tumor regression in the same animal model [1]. These findings highlight the efficacy of OTS964 in inducing complete regression of LU-99 lung cancer cells in nude mice, regardless of the route of administration.