Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Adavosertib (MK-1775) 是一种Wee1抑制剂,IC50值为 5.2 nM。它阻碍了 G2 DNA 损伤检查点。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 233 | 现货 | ||
2 mg | ¥ 329 | 现货 | ||
5 mg | ¥ 535 | 现货 | ||
10 mg | ¥ 859 | 现货 | ||
25 mg | ¥ 1,580 | 现货 | ||
50 mg | ¥ 2,490 | 现货 | ||
100 mg | ¥ 3,490 | 现货 | ||
200 mg | ¥ 4,990 | 现货 | ||
500 mg | ¥ 6,970 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 638 | 现货 |
产品描述 | Adavosertib (MK-1775) is a small molecule inhibitor of the checkpoint kinase WEE1 (IC50: 5.2 nM). It hinders the G2 DNA damage checkpoint. |
靶点活性 | Wee1:5.2 nM (cell free) |
体外活性 | MK-1775 (Adavosertib) inhibits phosphorylation of CDC2 at Tyr15 (CDC2Y15), a direct substrate of Wee1 kinase in cells. MK-1775 abrogates G(2) DNA damage checkpoint, leading to apoptosis in combination with DNA-damaging chemotherapeutic agents such as gemcitabine, carboplatin, and cisplatin selectively in p53-deficient cells [1]. Nanomolar concentrations of MK-1775 radiosensitized p53-defective human lung, breast, and prostate cancer cells but not similar lines with wild-type p53. Consistent with its ability to radiosensitize, MK-1775 abrogated the radiation-induced G? block in p53-defective cells but not in p53 wild-type lines [2]. |
体内活性 | Gemcitabine was administered to nude rats bearing WiDr (human colorectal) tumors at a dose of 50 mg/kg (i.v., bolus). Twenty-four hours later, MK-1775 was p.o. administered at a dose of 5, 10, or 20 mg/kg. Gemcitabine alone only moderately inhibited tumor growth. Cotreatment with MK-1775 significantly enhanced the antitumor effects in a dose-dependent manner and was well tolerated [1]. MK-1775 also significantly enhanced the antitumor efficacy of radiation in vivo as shown in tumor growth delay studies, again for p53-defective tumors [2]. |
激酶实验 | Kinase reaction was conducted with 10 μmol/L ATP, 1.0 μCi of [γ-33P]ATP, and 2.5 μg of poly(Lys, Tyr) as a substrate at 30°C for 30 min. Radioactivity incorporated into the substrate was trapped on MultiScreen-PH plates and was counted on a liquid scintillation counter [1]. |
细胞实验 | Tumor cells were cultured in 96-well plates and incubated with DNA-damaging agents for 24 h, then with MK-1775 and nocodazole for additional 8 h. For p-CDC2Y15 assay, cells were lysed and subjected in a colorimetric ELISA to determine the amounts of p-CDC2Y15 (1:100) and total CDC2 (1:200). For phospho-histone H3 (pHH3), cells were fixed with methanol, stained with anti-pHH3 specific antibody and bound antibody was stained with Alexa Fluor 488 goat anti-rabbit antibody. Images were acquired with an INCell Analyzer 1000 [1]. |
动物实验 | Subcutaneous xenograft tumors were formed by injection of the human cancer cell lines in the hind flank of immunodeficient nude rats (F344/NJcl-rnu). To facilitate tumor formation, cells were injected in medium containing Matrigel, a solubilized basement membrane preparation extracted from the Engelbreth-Holm-Swarm mouse sarcoma. Gemcitabine, carboplatin, and cisplatin were dissolved or diluted in saline and were dosed i.v. MK-1775 was prepared in a vehicle of 0.5% methylcellulose solution and was dosed p.o. 24 h after dosing DNA-damaging agents. For efficacy studies, tumor volumes were measured with a caliper every 3 d and body weights were determined each weekday. Statistical analysis was done using repeated-measure ANOVA followed by Dunnett's test for relative tumor volume. T/C (%) was calculated as (ΔT/ΔC) × 100 if ΔT > 0 or (ΔT/TI) × 100 if ΔT < 0. ΔT was the change in mean tumor volume to the initial tumor volume for the treatment group, and ΔC was the change in mean tumor volume to the initial tumor volume for the vehicle control group. Ti was the initial tumor volume of the treatment group [1]. |
别名 | AZD1775, MK-1775, Adavosertib (MK-1775) |
分子量 | 500.6 |
分子式 | C27H32N8O2 |
CAS No. | 955365-80-7 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 74 mg/mL (147.8 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.9976 mL | 9.988 mL | 19.976 mL | 49.9401 mL |
5 mM | 0.3995 mL | 1.9976 mL | 3.9952 mL | 9.988 mL | |
10 mM | 0.1998 mL | 0.9988 mL | 1.9976 mL | 4.994 mL | |
20 mM | 0.0999 mL | 0.4994 mL | 0.9988 mL | 2.497 mL | |
50 mM | 0.04 mL | 0.1998 mL | 0.3995 mL | 0.9988 mL | |
100 mM | 0.02 mL | 0.0999 mL | 0.1998 mL | 0.4994 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。
Adavosertib 955365-80-7 Cell Cycle/Checkpoint Wee1 AZD-1775 AZD1775 MK-1775 Adavosertib (MK-1775) AZD 1775 inhibit MK 1775 MK1775 Inhibitor inhibitor