OTS964 hydrochloride

SKU: orb1303110

Description

OTS964 hydrochloride is a potent and selective inhibitor of the TOPK (T-LAK cell-originated protein kinase), exhibiting anticancer properties. It has demonstrated efficacy in both in vitro cell-based assays and in vivo tumor models, making it a valuable research tool for oncology and signal transduction studies.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1338545-07-5
• MW: 428.97
• Purity: 98.03% (May vary between batches)
• Formula: C₂₃H₂₄N₂O₂S·HCl
• SMILES: Cl.C[C@@H](CN(C)C)c1ccc(cc1)-c1c(O)cc(C)c2[nH]c(=O)c3sccc3c12
• Target: Apoptosis,TOPK,CDK
• Solubility: DMSO:79 mg/mL (184.16 mM);Ethanol:1 mg/mL (2.33 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.66 mM)

Bioactivity

• Target IC50:
  TOPK:28 nM|CDK11B:40 nM (Kd)
• 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
• 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 290 nM. 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
• Cell Research:
  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.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:
  Animal Models: BALB/cSLC-nu/nu miceFormulation: 5% glucoseDosages: 40 mg/kgAdministration: i.v.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CDK, Apoptosis, OTS 964 Hydrochloride, OTS 964, OTS964, OTS-964, TOPK

Compound Identifiers

PubChem CID

89675898