OTS-964

Research use only, not for human use.

OTS-964 is a dimethylated derivative of OTS514 and potent, selective TOPK inhibitor with IC50 of 28 nM.

OTS-964 is a dimethylated derivative of OTS514 and potent, selective TOPK inhibitor with IC50 of 28 nM, exhibits excellent in vivo efficacy with liposomal formulation; inhibits the growth of TOPK-positive cells with low IC50 values (A549 IC50=31 nM), decreases autophosphorylation of TOPK (Thr9), as well as phosphorylation of histone H3 (Ser10), in both T47D and LU-99 cells; the liposomal OTS964 causes complete regression of tumors without any detectable toxicity in the xenograft models.

OTS964 hydrochloride (10 nM; 48 hours) suppresses cancer cell proliferation. OTS964 hydrochloride (10 nM; 48 hours) increases cancer cell death. 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. Cell Proliferation Assay Cell Line:LU-99 cells.Concentration:10 nM Incubation Time:48 hours Result:Suppressed cancer cell proliferation.Apoptosis Analysis Cell Line:LU-99 cells Concentration:10 nM Incubation Time:48 hoursResult:Increased cancer cell death.Western Blot AnalysisCell 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.

OTS964 hydrochloride (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. OTS964 hydrochloride (oral administration; 50 or 100 mg/kg/day for 2 weeks) ultimately achieves complete tumor regression. Animal Model:Nude mice bearing LU-99 lung cancer cells 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 cellsDosage:50 or 100 mg/kg Administration:Oral administration; once every day for 2 weeks Result:Achieved complete tumor regression.

OTS964

MAPK/ERK Signaling

MEK

TOPK

Cancer

——

1338545-07-5

428.9748

C23H25ClN2O2S

>98% (HPLC)

10 mM in DMSO

CC1=CC(=C(C2=C1NC(=O)C3=C2C=CS3)C4=CC=C(C=C4)C(C)CN(C)C)O.Cl

Thieno[2,3-c]quinolin-4(5H)-one, 9-[4-[(1R)-2-(dimethylamino)-1-methylethyl]phenyl]-8-hydroxy-6-methyl-, hydrochloride (1:1)

(-20℃)

With Ice Pack

≥ 2 years