Adavosertib （MK-1775）
目录号：S1525
Molecular Weight(MW): 500.6
MK-1775是一种有效的，高选择性Wee1抑制剂，无细胞试验中IC50为5.2 nM；阻碍G2期DNA损伤检验点。Phase 2。
客户使用该产品的7个实验数据：
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Panobinostat enhances the antitumor activity of MK-1775 in a BxPC-3 xenograft model. Tumor specimens were fixed in 10% formalin, embedded in paraffin, and cut into 4 μM-thick slides for H&E staining.
Cancer Letters, 2015, 356(200): 656–668 . Adavosertib （MK-1775） purchased from Selleck.
Diagnostic AML blasts from patients either at first diagnosis or at relapse are equally sensitive to MK-1775. Freshly isolated cells from patient AML#10 were purified by standard Ficoll-Hypaque density centrifugation. AML#10, HL-60, and HL-60/Ara-C cells were treated with MK-1775 for 48 h. Whole cell lysates were subjected to Western blotting and probed with anti-p-CDK1, -CDK1, -p-CDK2, -CDK2, -γH2AX, or -β-actin antibody.
J Hematol Oncol 2014 7:53. Adavosertib （MK-1775） purchased from Selleck.
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Front Oncol, 2018, 8:143. Adavosertib （MK-1775） purchased from Selleck.
(C) Nude mice bearing MDA-MB-231 xenograft tumors were treated with vehicle, MK-1775, cisplatin, or a combination of cisplatin and MK-1775 for 28 days and tumor volumes were measured. Data are presented as the mean of 8 tumors for each group ± SEM.
Sci Rep, 2017, 7:43517. Adavosertib （MK-1775） purchased from Selleck.
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GH activates STAT5 and ERK in breast cancer cells. T47D cells were pretreated for 2 hours with vehicle (dimethylsulfoxide) or inhibitors for EGFR (AG1478, 15 uM) or JAK2 (AZD1480, 1 uM), followed by treatment with GH+E2 for 30 minutes.
Endocrinology 2013 154(9), 3219-27. Adavosertib （MK-1775） purchased from Selleck.
AZD1480 inhibits the JAK2/STAT3 pathway in vitro. HT29 cells were cultured in 24-well plates overnight and then treated with 1 uM AZD1480 for 2 h followed by 4 ng/ml, IL-6 for 2 h and the distribution of phosphorylated STAT3 was analyzed by immunofluorescence.
Oncol Rep 2014 32(5), 1991-8. Adavosertib （MK-1775） purchased from Selleck.
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Histopathological assessment of tumor response to MK-1775 alone and in combination with gemcitabine in a patient-derived osteosarcoma mouse model. A. H&E-stained paraffin sections were prepared to assess microscopic features of cell death and differentiation representative micrographs of B. Ki67 shows high immunoreactivity in the control, MK-1775, and combination treatments compared to gemcitabine treatment. C. Cleaved-caspase 3 images show high immunoreactivity in the MK-1775 and combination treatments compared to vehicle and gemcitabine treatment. D. Slides stained for γH2AX show high immunoreactivity in gemcitabine, MK-1775, and combination treatments compared to controls. E. Slides stained for Cyclin A show higher immunoreactivity in gemcitabine but not in control, MK-1775 alone or in combination treatments.
PLoS One 2013 8(3), e57523. Adavosertib （MK-1775） purchased from Selleck.
产品安全说明书
Wee1抑制剂选择性比较
生物活性
| 产品描述 | MK-1775是一种有效的，高选择性Wee1抑制剂，无细胞试验中IC50为5.2 nM；阻碍G2期DNA损伤检验点。Phase 2。 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 特性 | 首个报道的 Wee1抑制剂。 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 靶点 |
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| 体外研究 |
MK-1775以ATP竞争的方式抑制Wee1激酶。与作用于Wee1相比，MK-1775对Yes的效能低2-到3-倍，IC50为14 nM，对7种其他激酶的效能低10倍，1 μM浓度下抑制率>80%，比对人Myt 1选择性高100倍以上，并抑制周期蛋白依赖性激酶1 (CDC2) 在可选择位点(Thr14) 的磷酸化作用。通过阻断负荷突变型p53的WiDr细胞中Wee1活性，废止DNA损伤检控点，MK-1775治疗抑制Tyr15 (CDC2Y15)位点的CDC2基础磷酸化作用，EC50为49 nM，并剂量依赖性抑制gemcitabine-，carboplatin- 或cisplatin-诱导的CDC2磷酸化和细胞周期阻滞，EC50分别为82 nM和81 nM，180 nM 和163 nM，以及159 nM 和 160 nM。30-100 nM 的MK-1775单独治疗在WiDr 和 H1299细胞中没有显著的抗增殖作用，而300 nM的MK-1775足以抑制>80%的Wee1，表现出温和但显著的抗增殖作用，在WiDr和H1299细胞中抑制率分别为34.1%和28.4%。[1] |
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| Cell Data |
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| 体内研究 | MK-1775(~20 mg/kg)单独治疗对WiDr异种移植物表现出最小的抗肿瘤作用，在大鼠体内第3天时T/C为69%。在裸鼠HeLa-luc和TOV21G-shp53异种移植模型中，MK-1775单独的抗肿瘤效能是温和的。[1] |
推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
| 激酶实验： |
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体外激酶试验: 使用重组人Wee1。激酶反应使用10 μM ATP，1.0 μCi of [γ-33P]ATP，和2.5 μg poly(Lys, Tyr)作为底物，在逐渐增加浓度的MK-1775存在下，在30°C环境中进行30分钟。整合到底物的放射性被捕获到MultiScreen-PH平板，在液体闪烁计数器上计数。 |
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| 细胞实验： |
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| 动物实验： |
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溶解度 (25°C)
| 体外 | DMSO | 80 mg/mL (159.8 mM) |
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| Ethanol | 10 mg/mL (19.97 mM) | |
| Water | 0.0001 mg/mL (0.0 mM) | |
| 体内 |
从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 2% DMSO+30% PEG 300+5% Tween 80+ddH2O |
5mg/mL |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 500.6 |
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| 化学式 | C27H32N8O2 |
| CAS号 | 955365-80-7 |
| 稳定性 | powder |
| in solvent | |
| 别名 | N/A |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01076400 | Terminated | Cervical Cancer | Merck Sharp & Dohme Corp. | May 31 2010 | Phase 1|Phase 2 |
| NCT01357161 | Completed | Ovarian Cancer | Merck Sharp & Dohme Corp. | July 26 2011 | Phase 2 |
| NCT02508246 | Active not recruiting | Head and Neck Squamous Cell Carcinoma | University of Washington|National Cancer Institute (NCI) | July 22 2015 | Phase 1 |
| NCT02101775 | Active not recruiting | Ovarian Brenner Tumor|Ovarian Carcinosarcoma|Ovarian Clear Cell Cystadenocarcinoma|Ovarian Endometrioid Adenocarcinoma|Ovarian Mucinous Cystadenocarcinoma|Ovarian Seromucinous Carcinoma|Ovarian Serous Cystadenocarcinoma|Ovarian Serous Surface Papillary Adenocarcinoma|Ovarian Undifferentiated Carcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma | National Cancer Institute (NCI) | July 21 2014 | Phase 2 |
| NCT02196168 | Terminated | Recurrent Hypopharyngeal Squamous Cell Carcinoma|Recurrent Laryngeal Squamous Cell Carcinoma|Recurrent Laryngeal Verrucous Carcinoma|Recurrent Lip and Oral Cavity Squamous Cell Carcinoma|Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary|Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma|Recurrent Oral Cavity Verrucous Carcinoma|Recurrent Oropharyngeal Squamous Cell Carcinoma|Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary|Stage IV Hypopharyngeal Squamous Cell Carcinoma|Stage IVA Laryngeal Squamous Cell Carcinoma|Stage IVA Laryngeal Verrucous Carcinoma|Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma|Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma|Stage IVA Oral Cavity Verrucous Carcinoma|Stage IVA Oropharyngeal Squamous Cell Carcinoma|Stage IVB Laryngeal Squamous Cell Carcinoma|Stage IVB Laryngeal Verrucous Carcinoma|Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma|Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma|Stage IVB Oral Cavity Verrucous Carcinoma|Stage IVB Oropharyngeal Squamous Cell Carcinoma|Stage IVC Laryngeal Squamous Cell Carcinoma|Stage IVC Laryngeal Verrucous Carcinoma|Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma|Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma|Stage IVC Oral Cavity Verrucous Carcinoma|Stage IVC Oropharyngeal Squamous Cell Carcinoma|Tongue Carcinoma | National Cancer Institute (NCI) | March 2014 | Phase 2 |
| NCT01164995 | Unknown status | Epithelial Ovarian Cancer | The Netherlands Cancer Institute|Merck Sharp & Dohme Corp. | July 2010 | Phase 2 |
技术支持
在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。
如果有其他问题，请给我们留言。
常见问题及建议解决方法
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问题 1：
How to prepare MK1775 methylcellulose solution? and how to prepare methylcellulose itself? Once make the MK1775 methylcellulose solution, how should i keep it?
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回答：
MK1775 in 0.5% methylcellulose is a suspension or emulsion, and it is ok to treat mice orally. It is recommended to dissolve methylcellulose in saline. It will take some time to dissolve methylcellulose, and you can vortex it for a while. The MK1775 methylcellulose solution can be stored at 4°C for a week.
