OTS-964

SKU: orb1226513

Description

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.

Key Properties

• CAS Number: 1338545-07-5
• MW: 428.9748
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₅ClN₂O₂S
• SMILES: CC1=CC(=C(C2=C1NC(=O)C3=C2C=CS3)C4=CC=C(C=C4)C(C)CN(C)C)O.Cl
• Target: MEK
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  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 cells. Dosage: 50 or 100 mg/kg. Administration: Oral administration; once every day for 2 weeks. Result: Achieved complete tumor regression.
• In Vitro:
  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 hours. Result: Increased cancer cell death. Western blot analysis. 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

OTS964

Quick Database Links

Gene Symbol

MEK