OTS514 hydrochloride

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].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> TOPK

IC50: 2.6 nM (TOPK)[1]

OTS514 (1.5625-100 nM) induces cell cycle arrest and apoptosis at nanomolar concentrations in a series of human myeloma cell lines (HMCL) and prevents outgrowth of a putative CD138+ stem cell population from multiple myeloma (MM) patient-derived peripheral blood mononuclear cells[2]. Cell Viability Assay[2] Cell Line: Human myeloma cell lines (MM1.S, MM1.R, RPMI 8226, 8226Dox40, KMS34, KMS34CFZ, KMS11, JJN3, LP-1, NCI H929, U266B1) Concentration: 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 nM Incubation Time: 72 hours Result: IC50 values ranged from 11.6 to 29.4 nM in parental cell lines, indicating a potent inhibitory effect. Only the RPMI 8226-Dox40 cell line, which overexpresses the multi-drug resistance transporter gene ABCB1, was resistant.

OTS514 (1-5 mg/kg; once a day for 2 weeks; intravenous administration) induces tumor regression in a xenograft model of A549 cells (TOPK-positive lung cancer cells)[1]. Animal Model: Female BALB/cSLC-nu/nu mice bearing a xenograft model of A549 cells[1] Dosage: 1, 2.5, and 5 mg/kg Administration: Intravenously treated; once every day for 2 weeks Result: Resulted in tumor growth inhibition (TGI) of 5.7, 43.3, and 65.3% on day 15, respectively, without any body weight loss.

[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.

[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.