OTS964

Catalog No.S7648 Batch:S764803

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Technical Data

Formula

C23H24N2O2S.HCl

Molecular Weight 428.97 CAS No. 1338545-07-5
Solubility (25°C)* In vitro DMSO 12 mg/mL (27.97 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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].

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 Assay:

[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 Study:

[1]

  • Animal Models

    BALB/cSLC-nu/nu mice

  • Dosages

    40 mg/kg

  • Administration

    i.v.

Selleck's OTS964 has been cited by 5 publications

P-TEFb promotes cell survival upon p53 activation by suppressing intrinsic apoptosis pathway [ Nucleic Acids Res, 2023, gkad001] PubMed: 36727434
Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth [ Cancer Lett, 2022, 544:215812] PubMed: 35780928
TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC [ Cell Death Dis, 2022, 13(5):450] PubMed: 35546143
SCFFBXW7 regulates G2-M progression through control of CCNL1 ubiquitination [ EMBO Rep, 2022, e55044] PubMed: 36278408
[18F]FE-OTS964: a Small Molecule Targeting TOPK for In Vivo PET Imaging in a Glioblastoma Xenograft Model [ Mol Imaging Biol, 2019, 21(4):705-712] PubMed: 30357568

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.