OTS964

Modify Date: 2024-01-03 10:59:00

OTS964 structure	Common Name	OTS964
	CAS Number	1338542-14-5	Molecular Weight	392.51
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₂₃H₂₄N₂O₂S	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of 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].

Name	OTS964

Description	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].
Related Catalog	Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer Signaling Pathways >> Cell Cycle/DNA Damage >> TOPK Signaling Pathways >> Cell Cycle/DNA Damage >> CDK
Target	TOPK:28 nM (IC50) CDK11B:40 nM (Kd)
In Vitro	OTS964 (10 nM; 48 hours) suppresses cancer cell proliferation[1]. OTS964 (10 nM; 48 hours) increases cancer cell death[1]. OTS964 (0.1-2 μM; 24 and 48 hours) increases the expression of LC3-II and decreases the expression of P62, both in a dose-dependent manner[3]. Cell Proliferation Assay[1] Cell Line: LU-99 cells Concentration: 10 nM Incubation Time: 48 hours Result: Suppressed cancer cell proliferation. Apoptosis Analysis[1] Cell Line: LU-99 cells Concentration: 10 nM Incubation Time: 48 hours Result: Increased cancer cell death. Western Blot Analysis[3] Cell Line: Hs683 cells, H4 cells Concentration: 0.1, 1, 2 μM Incubation Time: 24 and 48 hours Result: Increased the expression of LC3-II and decreased the expression of P62, both in a dose-dependent manner.
In Vivo	OTS964 (intravenously; 40 mg/kg on days 1, 4, 8, 11, 15, and 18) makes tumors shrinking even after the treatment and finally revealing complete regression[1]. OTS964 (oral administration; 50 or 100 mg/kg/day for 2 weeks) achieves complete tumor regression[1]. Animal Model: Nude mice bearing LU-99 lung cancer cells[1] Dosage: 40 mg/kg Administration: Intravenously; on days 1, 4, 8, 11, 15, and 18 Result: The tumors continued shrinking even after the treatment and finally revealed complete regression. Animal Model: Nude mice bearing LU-99 lung cancer cells[1] Dosage: 50 or 100 mg/kg Administration: Oral administration; once every day for 2 weeks Result: Achieved complete tumor regression.
References	[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. [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). [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.

Molecular Formula	C₂₃H₂₄N₂O₂S
Molecular Weight	392.51