OTS-964 - TOPK 抑制剂 - 生命科学试剂 - 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作靶点: TOPK作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 83.33 mg/mL (194.26 mM)* means soluble,

2、 but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄

3、清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.83 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.83 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small

4、Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.83 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 OTS-964种有效的选择性 T 淋巴细胞因激活杀伤细胞 性蛋激酶 (TOPK) 抑制剂，IC50 为 28 nM。IC50 & Target IC50: 28 nM (TOPK) 1体外研究 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.体内研究 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 您边的抑制剂师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.户使本产品发表的科研献 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.