Adavosertib (MK-1775)

别名: AZD1775

Adavosertib (MK-1775, AZD1775)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。

Adavosertib (MK-1775) Chemical Structure

Adavosertib (MK-1775) Chemical Structure

CAS: 955365-80-7

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 794.43 现货
5mg RMB 647.01 现货
10mg RMB 1040.13 现货
25mg RMB 1941.03 现货
100mg RMB 4823.91 现货
1g RMB 10401.3 现货
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客户使用Selleck的Adavosertib (MK-1775)发表文献203

产品质控

批次: 纯度: 99.99%
99.03

Adavosertib (MK-1775)相关产品

相关信号通路图

Wee1抑制剂选择性比较

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
CMY Cell Viability Assay 10-10000 nM 72 h reduces cell vialibity in a concentration-dependent manner 24962331
CMK Cell Viability Assay 10-10000 nM 72 h reduces cell vialibity in a concentration-dependent manner 24962331
MOLM-13 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
OCI-AML3 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
HL-60 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
U937 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
MV4-11 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
THP-1 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
SK-N-DZ Apoptosis Assay 500 nM 48 h induces cell apoptosis 25308916
SK-N-AS Apoptosis Assay 500 nM 48 h induces cell apoptosis 25308916
IST-MES1 Cell Viability Assay 150/250 nM 72 h enhances the cisplatin cytotoxic effect in a concentration-dependent manner 24365782
IST-MES2 Cell Viability Assay 150/250 nM 72 h enhances the cisplatin cytotoxic effect in a concentration-dependent manner 24365782
REN Cell Viability Assay 150/250 nM 72 h enhances the cisplatin cytotoxic effect in a concentration-dependent manner 24365782
NCI-H2452 Cell Viability Assay 150/250 nM 72 h enhances the cisplatin cytotoxic effect in a concentration-dependent manner 24365782
MSTO-211H Cell Viability Assay 150/250 nM 72 h enhances the cisplatin cytotoxic effect in a concentration-dependent manner 24365782
NCI-H2052 Cell Viability Assay 150/250 nM 72 h enhances the cisplatin cytotoxic effect in a concentration-dependent manner 24365782
T98G  Apoptosis Assay 100/250 nM 6 h enhances radiation-induced cell killing 21992793
A549 Apoptosis Assay 200 nM 1 h radiosensitizes NSCLC cells in a p53-dependent manner 21799033
H460 Apoptosis Assay 200 nM 1 h radiosensitizes NSCLC cells in a p53-dependent manner 21799033
H1299 Apoptosis Assay 200 nM 1 h radiosensitizes NSCLC cells in a p53-dependent manner 21799033
Calu-6  Apoptosis Assay 200 nM 1 h radiosensitizes NSCLC cells in a p53-dependent manner 21799033
WiDr Kinase Assays 10-10000 nM 8 h inhibits phosphorylation of CDC2 at Tyr15 with an EC50 value of 85 nmol/L pretreated with gemcitabine 19887545
Function assay MDA-MB-231 0.1 to 10 uM 6 hrs Inhibition of Wee1 in human MDA-MB-231 cells assessed as decrease in CDK1 phosphorylation at Tyr 15 at 0.1 to 10 uM after 6 hrs by Western blot method 28792760
Function assay HEK293T 0.1 to 10 uM 6 hrs Inhibition of Wee1 in HEK293T cells assessed as decrease in CDK1 phosphorylation at Tyr15 at 0.1 to 10 uM after 6 hrs by Western blot method 28792760
Function assay HEK293T 0.1 to 10 uM 6 hrs Inhibition of PLK1 in HEK293T cells assessed as decrease in TCTP phosphorylation at 0.1 to 10 uM after 6 hrs by Western blot method 28792760
Function assay MDA-MB-23 0.1 to 10 uM 6 hrs Inhibition of PLK1 in human MDA-MB-23 cells assessed as decrease in TCTP phosphorylation at 0.1 to 10 uM after 6 hrs by Western blot method 28792760
Antiproliferative assay MDA-MB-231 72 hrs Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by CellTiter-Blue assay, IC50 = 0.26 μM. 28792760
Antiproliferative assay HEK293T 72 hrs Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTiter-Blue assay, IC50 = 0.29 μM. 28792760
Antiproliferative assay MM1S 72 hrs Antiproliferative activity against human MM1S cells measured after 72 hrs by CellTiter-Blue assay, IC50 = 0.31 μM. 28792760
Function assay HEK293 1 hr Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, Ki = 0.47 μM. 29941193
Function assay HEK293 1 hr Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, IC50 = 4.94 μM. 29941193
Dayo Growth Inhibition Assay IC50=150 nM 24661910
SK-N-DZ Growth Inhibition Assay IC50=0.36 ± 0.01 μM 25308916
SK-N-AS Growth Inhibition Assay IC50=0.50 ± 0.02 μM 25308916
SK-N-BE (2), MK→PAN Growth Inhibition Assay IC50=2.4 ± 0.3 μM 25308916
SK-N-BE (2), PAN→MK Growth Inhibition Assay IC50=26.6 ± 9.6 μM 25308916
SK-N-BE (2) Growth Inhibition Assay IC50=2.4 ± 0.3 μM 25308916
PANC-1 Growth Inhibition Assay IC50=10.6 ± 1.1 μM 25458954
MIAPaCa-2 Growth Inhibition Assay IC50=0.5 ± 0.05 μM 25458954
HPAC Growth Inhibition Assay IC50=0.5 ± 0.01 μM 25458954
CFPAC-1 Growth Inhibition Assay IC50=3.3 ± 0.2 μM 25458954
BxPC-3 Growth Inhibition Assay IC50=0.8 ± 0.03 μM 25458954
ASPC-1 Growth Inhibition Assay IC50=13.2 ± 1.1 μM 25458954
UW228 Growth Inhibition Assay IC50=232 nM 24661910
WEE1 Growth Inhibition Assay IC50=5.2 nM 23699655
CDC2 Growth Inhibition Assay IC50>1000 nM 23699655
CDK7 Growth Inhibition Assay IC50>1000 nM 23699655
MYT1 Growth Inhibition Assay IC50=530 nM 23699655
Function assay Expi293F Binding affinity to recombinant human full-length N-terminal His8-tagged Wee1 (1 to 646 residues) expressed in human Expi293F cells assessed as dessociation constant by quantitative real-time PCR method, Kd = 0.0032 μM. 28792760
Function assay Expi293F Binding affinity to recombinant human full-length N-terminal His8-tagged Wee2 (1 to 567 residues) expressed in human Expi293F cells assessed as dessociation constant by quantitative real-time PCR method, Kd = 0.0039 μM. 28792760
qHTS assay TC32 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
qHTS assay U-2 OS qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
qHTS assay A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
qHTS assay DAOY qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
qHTS assay Saos-2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
qHTS assay BT-37 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
qHTS assay RD qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
qHTS assay SK-N-SH qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
qHTS assay BT-12 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
qHTS assay NB1643 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
qHTS assay OHS-50 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
qHTS assay BT-12 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
qHTS assay DAOY qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
qHTS assay SK-N-SH qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
qHTS assay Rh41 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
qHTS assay A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
qHTS assay MG 63 (6-TG R) qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
qHTS assay U-2 OS qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
qHTS assay OHS-50 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells 29435139
qHTS assay Rh41 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
qHTS assay RD qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
qHTS assay SJ-GBM2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
qHTS assay SK-N-MC qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
qHTS assay NB-EBc1 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
qHTS assay LAN-5 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
qHTS assay Rh18 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
qHTS assay SJ-GBM2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells 29435139
qHTS assay Saos-2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
点击查看更多细胞系数据

生物活性

产品描述 Adavosertib (MK-1775, AZD1775)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。
特性 首个报道的 Wee1抑制剂。
靶点
Wee1 [1]
(Cell-free assay)
5.2 nM
体外研究(In Vitro)
体外研究活性 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]
激酶实验 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。
细胞实验 细胞系 WiDr,NCI-H1299,TOV21G,和 HeLa细胞
浓度 在DMSO中溶解,终浓度为~10 μM
孵育时间 24小时
方法 细胞在gemcitabine存在或不存在下处理24小时,然后用MK-1775再处理24小时。细胞活性使用SpectraMax通过WST-8试剂盒测定。细胞内caspase-3/7活性使用Caspase-3/7 Glo试剂盒测定。
实验图片 检测方法 检测指标 实验图片 PMID
Western blot WEE1 PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15) p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345) p-Cdk1(Y15) / Cdk1 27616351
Immunofluorescence Cleaved caspase-3 / pH3 γH2AX tubulin / p-HH3(S10) 27616351
Growth inhibition assay IC50 Cell viability 25084614
体内研究(In Vivo)
体内研究活性 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]
动物实验 Animal Models 负荷WiDr,HeLa-luc,或TOV21G-shp53肿瘤的免疫缺陷裸鼠(F344/NJcl-rnu)
Dosages ~20 mg/kg/day
Administration 口服
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03253679 Completed
Advanced Malignant Solid Neoplasm|Refractory Malignant Solid Neoplasm
National Cancer Institute (NCI)
January 16 2019 Phase 2
NCT03668340 Active not recruiting
Uterine Cancer
Dana-Farber Cancer Institute|AstraZeneca
October 22 2018 Phase 2
NCT03028766 Completed
Hypopharynx Squamous Cell Carcinoma|Oral Cavity Squamous Cell Carcinoma|Larynx Cancer
University of Birmingham|AstraZeneca|Cancer Research UK
June 22 2017 Phase 1

化学信息&溶解度

分子量 500.6 分子式

C27H32N8O2

CAS号 955365-80-7 SDF Download Adavosertib (MK-1775) SDF
Smiles CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 100 mg/mL ( 199.76 mM; DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩尔浓度计算器

体内溶解度
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

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常见问题及建议解决方法

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?

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.

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