Adavosertib (MK-1775)

别名: AZD1775

目录号：S1525 Purity: 99.99%

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

CAS: 955365-80-7

规格	价格	库存
10mM (1mL in DMSO)	794.43	现货
5mg	647.01	现货
25mg	1941.03	现货
100mg	4823.91	现货
1g	10401.3	现货
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产品质控

批次：纯度： 99.99%

99.99

Adavosertib (MK-1775)相关产品

相关产品	PD0166285	点击展开
相关化合物库	激酶抑制剂库 PI3K/Akt 抑制剂库 MAPK抑制剂库 DNA损伤/ DNA修复化合物库细胞周期化合物库	点击展开

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
激酶实验	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	p-Cdk1(Y15) / Cdk1 p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345) PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15) WEE1		25609063
	Immunofluorescence	tubulin / p-HH3(S10) γH2AX Cleaved caspase-3 / pH3		30755439
	Growth inhibition assay	Cell viability IC50		25458954

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
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考文献
[1] Hirai H, et al. Mol Cancer Ther, 2009, 8(11), 2992-3000.

参考文献

[1] Hirai H, et al. Mol Cancer Ther, 2009, 8(11), 2992-3000.

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)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

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

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)

Ethanol : 10 mg/mL (19.97 mM)

Water : Insoluble

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

体内溶解配方批次：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
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
澄清溶液	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	12.000mg/ml (23.97mM)	以 1 mL 工作液为例，取 50 μL 240 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀使其澄清；向上述体系中加入50 μL Tween-80，混合均匀使其澄清；然后继续加入 500 μLddH2O定容至 1 mL。工作液请现配现用！
澄清溶液	5%DMSO 1 95% Corn oil 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	6.000mg/ml (11.99mM)	以 1 mL 工作液为例，取 50 μL 120 mg/mL 的澄清 DMSO 储备液加到 950 μL玉米油中，混合均匀。工作液请现配现用！
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
澄清溶液	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	5.000mg/ml (9.99mM)	以 1 mL 工作液为例，取 50 μL 100 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀使其澄清；向上述体系中加入50 μL Tween-80，混合均匀使其澄清；然后继续加入 500 μLddH2O定容至 1 mL。工作液请现配现用！

实验计算

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

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）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

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，注：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：取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：取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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操作手册

如果有其他问题，请给我们留言。

* 必填项

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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Adavosertib (MK-1775)

产品质控

Adavosertib (MK-1775)相关产品

相关信号通路图

细胞实验数据示例

生物活性

化学信息&溶解度

实验计算

技术支持

常见问题及建议解决方法