OTS964

Catalog No.S7648

For research use only.

OTS964 is a potent TOPK inhibitor with high affinity and selectivity and IC50 value is 28 nM. OTS964 is also a potent inhibitor of the cyclin-dependent kinase CDK11 with Kd of 40 nM. OTS964 treatment activates autophagy in glioma cells and induces apoptosis of human lung cancer cells in mouse xenografts.

OTS964 Chemical Structure

CAS No. 1338545-07-5

Selleck's OTS964 has been cited by 1 Publication

Purity & Quality Control

Choose Selective TOPK Inhibitors

Biological Activity

Description OTS964 is a potent TOPK inhibitor with high affinity and selectivity and IC50 value is 28 nM. OTS964 is also a potent inhibitor of the cyclin-dependent kinase CDK11 with Kd of 40 nM. OTS964 treatment activates autophagy in glioma cells and induces apoptosis of human lung cancer cells in mouse xenografts.
Targets
TOPK [1]
(Cell-free assay)
CDK11B [2]
(Cell-free assay)
28 nM 40 nM(Kd)
In vitro

OTS964 inhibits the growth of TOPK-positive cells with low IC50 values [A549 (31 nM), LU-99 (7.6 nM), DU4475 (53 nM), MDAMB- 231 (73 nM), T47D (72 nM), Daudi (25 nM), UM-UC-3 (32 nM), HCT-116 (33 nM),MKN1 (38 nM), MKN45 (39 nM), HepG2 (19 nM), MIAPaca-2 (30 nM), and 22Rv1 (50 nM)], whereas its growth inhibitory effect against TOPK-negative HT29 cancer cells is significantly weaker, with IC50 of 290nM. Although OTS964 reveals some suppressive effect on Src family kinases, the response to OTS964 in these cancer cells is not correlated with the expression of Src family kinases c-Src, Fyn, and Lyn, supporting the TOPK-dependent growth inhibitory effects of OTS964. Time lapse imaging in T47D cells shows that treatment with OTS964 induces cytokinesis defects followed by apoptosis[1].

Assay
Methods Test Index PMID
Western blot p62 / LC3-I / LC-3Ⅱ / p-Histone H3 / Histone H3 / TOPK ; ULK1 / p-ATG13 / ATG13 / p-Beclin-1 / Beclin-1 31378785
In vivo

Although administration of the free compound induces hematopoietic adverse reactions (leukocytopenia associated with thrombocytosis), the drug delivered in a liposomal formulation effectively causes complete regression of transplanted tumors without showing any adverse reactions in mice. Inhibition of TOPK activity with the liposomal OTS964 suppresses tumor growth through induction of cytokinesis defects and subsequent apoptosis. Although oral administration of OTS964 causes some hematopoietic toxicity, this is a transient effect. The spontaneous recovery from leukocytopenia is occured and the anticancer effectiveness of the oral drug is similar to that of the liposomal formulation, oral administration of the drug may prove to be more practical[1].

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: A549 cells, LU-99 cells, DU4475 cells, MDA-MB-231 cells, T47D cells, Daudi cells, UM-UC-3 cells, HCT-116 cells, MKN1 cells, MKN45 cells, HepG2 cells, MIAPaca-2 cells, 22Rv1 cells and HT29 cells
  • Concentrations: --
  • Incubation Time: 72 h
  • Method:

    Cells (100 μl) are plated in 96-well plates at a certain density. The cells are allowed to adhere overnight before exposure to compounds for 72 hours at 37°C. Plates are read with a spectrophotometer at a wavelength of 450 nm. All assays are carried out in triplicate. After measuring IC50 values, we calculates the z scores to produce P values. After log transformation (base 10) of IC50 values (nM), the mean and SD are calculated for the log values of the IC50 for the 13 TOPK-positive cell lines.

Animal Research:

[1]

  • Animal Models: BALB/cSLC-nu/nu mice
  • Dosages: 40 mg/kg
  • Administration: i.v.

Solubility (25°C)

In vitro

DMSO 85 mg/mL
(198.14 mM)
Ethanol 1 mg/mL
(2.33 mM)
Water Insoluble

Chemical Information

Molecular Weight 428.97
Formula

C23H24N2O2S.HCl

CAS No. 1338545-07-5
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC(=C(C2=C1NC(=O)C3=C2C=CS3)C4=CC=C(C=C4)C(C)CN(C)C)O.Cl

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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