Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Silmitasertib (CX-4945) 是一种可口服的高度选择性 CK2抑制剂,Ki 为 0.38 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 372 | 现货 | ||
2 mg | ¥ 538 | 现货 | ||
5 mg | ¥ 828 | 现货 | ||
10 mg | ¥ 1,330 | 现货 | ||
25 mg | ¥ 2,480 | 现货 | ||
50 mg | ¥ 3,750 | 现货 | ||
100 mg | ¥ 5,390 | 现货 | ||
500 mg | ¥ 11,200 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 987 | 现货 |
产品描述 | Silmitasertib (CX-4945) is a potent, orally bioavailable inhibitor of casein kinase 2 (CK2; Ki: 0.38 nM). |
靶点活性 | CK2:1 nM (cell free) |
体外活性 | The antiproliferative activity of Silmitasertib (CX-4945) against cancer cells correlated with expression levels of the CK2α catalytic subunit. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. In models of angiogenesis, CX-4945 inhibited human umbilical vein endothelial cell migration, tube formation, and blocked CK2-dependent HIF-1α transcription in cancer cells [1]. Adding CX-4945 after bortezomib treatment, prevented leukemic cells from engaging a functional UPR in order to buffer the bortezomib-mediated proteotoxic stress in ER lumen. Bortezomib/CX-4945 treatment inhibited NF-κB signaling in T-ALL cell lines and primary cells from T-ALL patients, but, in B-ALL cells the drug combination activated NF-κB p65 pro-apoptotic functions [2]. CX-4945 was found to potently inhibit endogenous intracellular CK2 activity with an IC50 of 0.1 μM in Jurkat cells. CX-4945 induced dephosphorylation of Akt(S129) and a rapid dephosphorylation of the Akt substrate p21(T145). CX-4945 induced apoptosis in multiple cancer cell lines [3]. |
体内活性 | When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145) [1]. Mice bearing subcutaneous PC3 tumors were treated with CX-4945 (25 mg/kg, 50 mg/kg, and 75 mg/kg, po, bid). Tumor growth inhibition compared to vehicle-treated control, and a dose-responsive efficacy was observed. Last, CX-4945 was well tolerated in mice as assessed by minimal changes in body weight during the course of treatment compared to vehicle control [3]. |
激酶实验 | The 238 kinase selectivity panel was conducted using the Kinase Profiler service, which utilizes a radiometric filter-binding assay. The percent inhibition of each kinase was estimated using 0.5 μmol/L CX-4945 at ATP concentrations equivalent to the Km value for ATP for each respective human recombinant kinase. The determination of IC50 values was done at ATP concentrations equivalent to the Km for ATP for each kinase using 9 concentrations of CX-4945 over a range of 0.0001 to 1 μmol/L. The Ki value (inhibition constant) for CX-4945 against recombinant CK2 was determined by graphing the IC50 values of CX-4945 determined in the presence of various concentrations of ATP against the concentration of ATP. The Ki value is equivalent to the Y-intercept according to the Cheng–Prussoff equation (Ki = IC50/(1+[ATP]/Km), where Ki is the inhibition constant and Km is the Michaelis constant [1]. |
细胞实验 | Various cell lines were seeded at a density of 3000 cells per well 24 h prior to treatment, in appropriate media, and then treated with indicated concentrations of CK2 inhibitors. Suspension cells were seeded and treated on the same day. Following 4 days of incubation, 20 μL of Alamar Blue (10% of volume/well) was added and the cells were further incubated at 37 °C for 4-5 h. Fluorescence with excitation wavelength at 530-560 nm and emission wavelength at 590 nm was measured [3]. |
动物实验 | Xenografts were initiated by subcutaneous injection of BxPC-3 cells into the right hind flank region of each mouse or BT-474 cells were injected into the mammary fat pad of mice implanted with estrogen pellets. When tumors reached a designated volume of 150-200 mm^3, animals were randomized and divided into groups of 9 to 10 mice per group. CX-4945 was administered by oral gavage twice daily at 25 or 75 mg/kg for 31 and 35 consecutive days for the BT-474 and BxPC-3 models, respectively. Tumor volumes and body weights were measured twice weekly. The length and width of the tumor were measured with calipers and the volume calculated using the following formula: tumor volume = (length × width^2)/2. Percent tumor growth inhibition (TGI) values were calculated on the final day of the study for CX-4945–treated compared to vehicle-treated mice and were calculated as 100 × {1 ? [(TreatedFinal day ? TreatedDay 1)/(ControlFinal day ? ControlDay 1)]}. The significance of the differences between the treated versus vehicle groups were determined using 1-way ANOVA [1]. |
别名 | CX-4945, 5-[(3-氯苯基)氨基]-苯并[C]-2,6-萘啶-8-羧酸 |
分子量 | 349.77 |
分子式 | C19H12ClN3O2 |
CAS No. | 1009820-21-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
H2O: < 1 mg/mL (insoluble or slightly soluble)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 13 mg/mL (37.2 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.859 mL | 14.2951 mL | 28.5902 mL | 71.4755 mL |
5 mM | 0.5718 mL | 2.859 mL | 5.718 mL | 14.2951 mL | |
10 mM | 0.2859 mL | 1.4295 mL | 2.859 mL | 7.1476 mL | |
20 mM | 0.143 mL | 0.7148 mL | 1.4295 mL | 3.5738 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Silmitasertib 1009820-21-6 Autophagy Metabolism Stem Cells Casein Kinase Inhibitor inhibit CX-4945 CX4945 CX 4945 5-[(3-氯苯基)氨基]-苯并[C]-2,6-萘啶-8-羧酸 inhibitor