Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Dinaciclib (SCH 727965) 是一种选择性 CDK 抑制剂,抑制 CDK2,CDK5,CDK1和 CDK9的 IC50分别为 1 nM,1 nM,3 nM 和 4 nM。它具有潜在的抗肿瘤活性。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
2 mg | ¥ 498 | 现货 | ||
5 mg | ¥ 797 | 现货 | ||
10 mg | ¥ 1,240 | 现货 | ||
50 mg | ¥ 3,781 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 877 | 现货 |
产品描述 | Dinaciclib (SCH 727965) is a new-type and effective CDK inhibitor for CDK2/5/1/9 (IC50: 1 nM/1 nM/3 nM/4 nM) with potential antineoplastic activity. |
靶点活性 | CDK1:3 nM (cell free), CDK9:4 nM (cell free), CDK5:1 nM (cell free), CDK2:1 nM (cell free) |
体外活性 | Dinaciclib (SCH 727965) inhibits CDK2, CDK5, CDK1, and CDK9 activity in vitro with IC50 values of 1, 1, 3, and 4 nmol/L, respectively. In cell-based assays, SCH 727965 completely suppressed retinoblastoma phosphorylation, which correlated with apoptosis onset and total inhibition of bromodeoxyuridine incorporation in >100 tumor cell lines of diverse origin and background [1]. SCH 727965 (SCH) induces the apoptosis of several osteosarcoma cell lines including those resistant to doxorubicin and dasatinib. Apoptosis occurred at low nanomolar concentrations of SCH, as did CDK inhibition, and was p53-independent [2]. Treatment with SCH727965 significantly reduced in vitro cell growth, motility and colony formation in soft agar of MIAPaCa-2 and Pa20C cells [3]. |
体内活性 | SCH 727965 induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level [1]. Single-agent therapy with SCH727965 (40 mg/kg i.p. twice weekly) for 4 weeks significantly reduced subcutaneous tumor growth in 10/10 (100%) of tested low-passage human pancreatic cancer xenografts. Treatment of low passage pancreatic cancer xenografts with a combination of SCH727965 and gemcitabine was significantly more effective than either agent alone [3]. |
激酶实验 | Recombinant cyclin/CDK holoenzymes were purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK. Cyclin/CDK complexes were typically diluted to a final concentration of 50 μg/mL in a kinase reaction buffer containing 50 mmol/L Tris-HCl (pH 8.0), 10 mmol/L MgCl2, 1 mmol/L DTT, and 0.1 mmol/L sodium orthovanadate. For each kinase reaction, 1 μg of enzyme and 20 μL of a 2-μmol/L substrate solution (a biotinylated peptide derived from histone H1) were mixed and combined with 10 μL of diluted SCH 727965. The reaction was started by the addition of 50 μL of 2 μmol/L ATP and 0.1 μCi of 33P-ATP. Kinase reactions were incubated for 1 hour at room temperature and were stopped by the addition of 0.1% Triton X-100, 1 mmol/L ATP, 5 mmol/L EDTA, and 5 mg/mL streptavidin-coated SPA beads. SPA beads were captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads were washed twice with 2 mol/L NaCl and twice with 2 mol/L NaCl containing 1% phosphoric acid. The signal was then assayed using a TopCount 96-well liquid scintillation counter. Dose-response curves were generated from duplicate, eight-point serial dilutions of inhibitory compounds. IC50 values were derived by nonlinear regression analysis [1]. |
细胞实验 | A2780 cells were plated into six-well tissue culture dishes and allowed to adhere. Cells were then exposed to differing concentrations of SCH 727965 or a DMSO control vehicle for 24 hours, followed by a brief (30 min) pulsed exposure to bromodeoxyuridine (BrdUrd). Cells were then harvested, immunostained using FITC-conjugated antibodies specific for BrdUrd, counter-stained with propidium iodide/RNase A solution, and analyzed using flow cytometry. Fluorescence-activated cell sorting analyses were done on a FACSCalibur instrument. FITC-positive BrdUrd staining and propidium iodide signal allowed assessment of ongoing DNA replication and the cell cycle stage. Percentages of the cell population in each cell cycle stage were plotted for each test article concentration [1]. |
动物实验 | For tumor implantation, specific cell lines were grown in vitro, washed once with PBS, and resuspended in 50% Matrigel in PBS to a final concentration of 4 × 10^7 to 5 × 10^7 cells per milliliter. Nude mice were injected with 0.1 mL of this suspension s.c. in the flank region. Tumor length (L), width (W), and height (H) were measured by a caliper twice weekly on each mouse and then used to calculate tumor volume using the formula (L × W × H)/2. When the tumor volume reached ~100 mm^3, the animals were randomized to treatment groups (10 mice/group) and treated i.p. with either SCH 727965 or individual chemotherapeutic agents according to the dosing schedule indicated in table and figure legends. Tumor volumes and body weights were measured during and after the treatment periods. Data were expressed as means ± SEM. Animals were euthanized according to the Institutional Animal Care and Use Committee guidelines [1]. |
别名 | SCH 727965, PS-095760 |
化合物与蛋白结合的复合物 |
BRDT in complex with Dinaciclib |
分子量 | 396.49 |
分子式 | C21H28N6O2 |
CAS No. | 779353-01-4 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 50 mg/mL (126.11 mM)
Ethanol: 8 mg/mL (20.17 mM), warmed
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO / Ethanol | 1 mM | 2.5221 mL | 12.6107 mL | 25.2213 mL | 63.0533 mL |
5 mM | 0.5044 mL | 2.5221 mL | 5.0443 mL | 12.6107 mL | |
10 mM | 0.2522 mL | 1.2611 mL | 2.5221 mL | 6.3053 mL | |
20 mM | 0.1261 mL | 0.6305 mL | 1.2611 mL | 3.1527 mL | |
DMSO | 50 mM | 0.0504 mL | 0.2522 mL | 0.5044 mL | 1.2611 mL |
100 mM | 0.0252 mL | 0.1261 mL | 0.2522 mL | 0.6305 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。
Dinaciclib 779353-01-4 Apoptosis Cell Cycle/Checkpoint CDK inhibit Inhibitor SCH 727965 SCH727965 PS-095760 Cyclin dependent kinase PS095760 PS 095760 SCH-727965 inhibitor