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OTS514 hydrochloride is a highly potent TOPK inhibitor, which inhibits TOPK kinase activity with a median inhibitory concentration (IC50) value of 2.6 nM. OTS514 hydrochloride strongly suppresses the growth of TOPK-positive cancer cells[1]. OTS514 hydrochloride induces cell cycle arrest and apoptosis[2].

OTS514 hydrochloride is a potent TOPK inhibitor with IC50 of 2.6 nM,it induces cell cycle arrest and apoptosis.

OTS514 has growth inhibitory effect on five TOPK-expressing renal cancer cell lines VMRC-RCW, Caki-1, Caki-2, 769-P and 786-O with IC50 ranging from 19.9-44.1 nM. OTS514 can effectively inhibit the growth of TOPK-expressing cancer cells with IC50 ranging from 3-46 nM for the growth inhibition of ovarian cancer cells.

Mouse xenograft studies (bearing human lung cancer cells) showed that OTS514 has antitumor activity in vivo, but also caused severe hematopoietic cytotoxicity (reduction of red and white blood cells, thrombocytosis). Oral administration of OTS514 significantly prolonged the lifespan of ES-2 abdominally infected xenograft mice.

Target	Value
TOPK (Cell-free assay)	2.6 nM

[1] Matsuo Y, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci Transl Med. 2014 Oct 22;6(259):259ra145. DOI:10.1126/scitranslmed.3010277
[2] Stefka AT, et al. Potent anti-myeloma activity of the TOPK inhibitor OTS514 in pre-clinical models. Cancer Med. 2020 Jan;9(1):324-334. DOI:10.1002/cam4.2695