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OTS514

Catalog No.GC12304

TOPK inhibitor,highly potent

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OTS514 Chemical Structure

Cas No.: 1338540-63-8

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5mg
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10mg
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

CD34+ HSCs are cultured in RPMI supplemented with 20% fetal bovine serum and 1× StemSpan CC100. Cells are treated with OTS514 (20 or 40 nM) or OTS-964 (100 or 200 nM) for 48 hours. Collected cells are washed with phosphate-buffered saline (PBS) and resuspended in 100 μL of PBS followed by staining with CD41a antibody for 20 min at room temperature. Finally, the cells are washed with PBS again and then analyzed for CD41a staining by flow cytometry on the BD FACSCalibur. Expression of STAT5 is examined by Western blot with an anti-STAT5 antibody[1].

Animal experiment:

Mice[1]A549 (1×107 cells) or LU-99 cells (5×106 or 1×107 cells) are injected subcutaneously in the left flank of female BALB/cSLC-nu/nu mice. When A549 xenografts have reached an average volume of 200 mm3 or when LU-99 xenografts have reached an average volume of 150 or 200 mm3, animals are randomized into groups of six mice. The in vivo antitumor effect of OTS514 is first investigated in a xenograft model of A549 cells (TOPK-positive lung cancer cells). OTS514 is administered to mice bearing A549 cells after the tumor size reaches about 200 mm3. Mice are intravenously treated with OTS514 (1, 2.5, and 5 mg/kg) once a day for 2 weeks. The tumor size is measured as a surrogate marker of drug response, and the percentage of tumor growth inhibition (TGI) is calculated. The antitumor effect of OTS514 is further investigated tin another lung cancer xenograft model of LU-99 cells. OTS514 is administered to mice bearing LU-99 cancer cells after the tumor size reaches about 200 mm3. Mice are intravenously treated with OTS514 (5 mg/kg) once a day for 2 weeks. Tumor volumes are determined using a caliper. The weight of the mice is determined as an indicator of tolerability on the same days[1].

References:

[1]. Matsuo Y, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci Transl Med. 2014 Oct 22;6(259):259ra145.

Background

OTS514, a thieno[2,3-c]quinolone compound, is a highly potent TOPK inhibitor with an IC50 value of 2.6 nM. The compound can inhibit TOPK kinase activity. TOPK (T-lymphokine-activated killer cell-originated protein kinase) is a protein that is found in a wide range of human cancers and is believed to work as an oncogene, promoting tumor growth.

It has been reported that OTS514 strongly inhibited the growth of the TOPK-positive cancer cell lines with low IC50 values ranging from 1.5 to 14 nM. While in HT29 cells, in which TOPK expression was little detectable, the IC50 value was 170 nM. Intravenous administration of free OTS514 at 1, 2.5, and 5mg/kg once a day for 2 weeks resulted in tumor growth Inhibition(TGI)of 5.7, 43.3, and 65.3% on day 15, respectively, without anybody weight loss. However, this inhibition also cause dysfunction in the differentiation process of hematopoietic stemcells (HSCs) to WBCs and RBCs but may enhance the differentiation of HSCs to megakaryocytes and platelets.

The antitumor effect of OTS514 in lung cancer xenograft model of LU-99 cells has also been investigated. OTS514 was administered to mice bearing LU-99 cancer cells after the tumor size reached about 200mm3. Intravenous administration of OTS514 (5 mg/kg) once a day for 2 weeks achieved good growth-suppressive effect with TGI of 104% without any body weight loss. However, the antitumor effect of OTS514 against LU-99 xenograft caused a significant reduction of WBCs.

References:
1. Matsuo Y, Park JH2, Miyamoto T, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. ci Transl Med. 2014 Oct 22;6(259):259ra145.
2. Y. Nakamura, Y. Matsuo, S. Hisada, et al. Tricyclic compounds and PBK inhibitors containing the same. Patent WO/2011/123419 (2011)

Chemical Properties

Cas No. 1338540-63-8 SDF
Chemical Name (R)-9-(4-(1-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one
Canonical SMILES NC[C@H](C)C1=CC=C(C2=C(O)C=CC3=C2C(C=CS4)=C4C(N3)=O)C=C1
Formula C21H20N2O2S M.Wt 364.46
Solubility DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.25 mg/ml Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.7438 mL 13.7189 mL 27.4379 mL
5 mM 0.5488 mL 2.7438 mL 5.4876 mL
10 mM 0.2744 mL 1.3719 mL 2.7438 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 18 reference(s) in Google Scholar.)

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