OTS964

OTS964 is an orally active, high affinity and selective TOPK inhibitor with an IC50 of 28 nM[1]. OTS964 is also a potent inhibitor of the cyclin-dependent kinase CDK11, which binds to CDK11B with a Kd of 40 nM[2].

TOPK: 28 nM (IC₅₀); CDK11B: 40 nM (Kd)

[1] Matsuo Y , et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancerthrough inhibition of cytokinesis. Sci Transl Med. 2014 Oct 22;6(259):259ra145. DOI:10.1126/scitranslmed.3010277
[2] Lin A, et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci Transl Med. 2019 Sep 11;11(509). DOI:10.1126/scitranslmed.aaw8412
[3] Lu H, et al. TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell Death Dis. 2019 Aug 5;10(8):583. DOI:10.1038/s41419-019-1805-9