OTS-964 - TOPK 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOTS-964Cat. No.: HY-12467CAS No.: 1338545-07-5分式: CHClNOS分量: 428.97作靶點(diǎn): TOPK作通路: Cell Cycle/DNA Damage儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 83.33 mg/mL (194.26 mM)* means soluble,

2、 but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3312 mL 11.6558 mL 23.3117 mL5 mM 0.4662 mL 2.3312 mL 4.6623 mL10 mM 0.2331 mL 1.1656 mL 2.3312 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄

3、清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.83 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.83 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small

4、Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.83 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 OTS-964種有效的選擇性 T 淋巴細(xì)胞因激活殺傷細(xì)胞 性蛋激酶 (TOPK) 抑制劑，IC50 為 28 nM。IC50 & Target IC50: 28 nM (TOPK) 1體外研究 OTS-964 (OTS964) inhibits the growth of TOPK-positive cells with low IC50 values A549 (31 nM), LU-99(7.6

5、 nM), DU4475 (53 nM), MDA-MB-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 (P=1.4510-4)weaker,

6、with IC50 of 290 nM. Although OTS-964 reveals some suppressive effect on Src family kinases, theresponse to OTS-964 in these cancer cells is not correlated with the expression of Src family kinases c-Src,Fyn, and Lyn. Treatment with OTS-964 decreases autophosphorylation of TOPK (Thr9), as well aspho

7、sphorylation of histone H3 (Ser10), in both T47D and LU-99 cells. Moreover, time lapse imaging in T47Dcells shows that treatment with OTS-964 induces cytokinesis defects followed by apoptosis, which is notobserved in control DMSO-treated T47D cells 1.體內(nèi)研究 Three LU-99 xenograft mice are intravenously

8、 treated with liposomal OTS-964 (40 mg/kg) or vehicle at days1, 4, 8, and 11, and tumors are collected on day 12. The cellular morphological changes and apoptosis areexamined t in the LU-99 cells. Treatment with OTS-964 induced irregular cell morphology with cytokinesisdefects. Treatment with OTS-96

9、4 significantly increases the number of LU-99 cells with the “intercellularbridge” (P 1.PROTOCOLCell Assay 1 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 ce

10、lls arewashed with phosphate-buffered saline (PBS) and resuspended in 100 L of PBS followed by staining withCD41a antibody for 20 min at room temperature. Finally, the cells are washed with PBS again and thenanalyzed for CD41a staining by flow cytometry on the BD FACSCalibur. Expression of STAT5 is

11、examinedby Western blot with an anti-STAT5 antibody 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 A549 (1107 cells) or LU-99 cells (5106 or 1107 cells) are injected subcutaneously in the left flank offemale BALB/cSLC-nu

12、/nu mice. When A549 xenografts have reached an average volume of 200 mm3 orwhen LU-99 xenografts have reached an average volume of 150 or 200 mm3, animals are randomized intogroups of six mice. The starting tumor volume of 150 mm3 is used for LU-99 xenografts when tumors aremonitored for a longer ti

13、me period (14 days), because LU-99 cells grow very rapidly, and thus the startingvolume of 200 mm3 prevents longer observation considering animal ethics (for example, 200 mm3 of2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEinoculated LU-99 tumor reaches an average tumor volume of about 1100 mm3,

14、whereas A549 tumorreaches about 490 mm3 on day 15). For intravenous administration, three LU-99 xenograft mice areintravenously treated with liposomal OTS-964 (40 mg/kg) into the tail vein or vehicle at days 1, 4, 8, and 11,and tumors are collected on day 12. For oral administration, OTS-964 is trea

15、ted at 50 or 100 mg/kg onceevery day for 2 weeks. An administration volume of 10 mL/kg of body weight is used for both administrationroutes. Concentrations are indicated in the main text and figures. Tumor volumes are determined using acaliper. The weight of the mice is determined as an indicator of

16、 tolerability on the same days 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Death Dis. 2019 Aug.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Matsuo Y, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibitionofcytokinesis.