OTS514

OTS514 is a potent and highly specific small molecule inhibitor of T-LAK cell-originated protein kinase, also known as PDZ-binding kinase (TOPK/PBK). TOPK is a mitotic kinase upregulated in various cancers and is involved in tumor cell proliferation, maintenance of cancer stem cells, and poor prognosis. OTS514 induces cell cycle arrest and apoptosis by activating FOXO3 and cyclin-dependent kinase inhibitors (CDKN1A/p21 and CDKN1B/p27), while disrupting oncogenic pathways including FOXM1, AKT, p38 MAPK, and NF-κB signaling. OTS514 demonstrates rapid and selective cytotoxicity toward cancer cells—including multiple myeloma, ovarian, lung, prostate, and kidney cancer cells—at nanomolar concentrations. In preclinical mouse models, OTS514 and its orally bioavailable analog OTS964 significantly reduced tumor sizes and showed synergistic effects when combined with existing anti-myeloma drugs such as lenalidomide. OTS514 has also been explored for use as a molecular probe for imaging tumors, emphasizing its target specificity for TOPK[1][2][3][5][7].