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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400-668-6834 info@selleck.cn

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(PMID)
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
https://pubmed.ncbi.nlm.nih.gov/19887545/

参考文献

https://pubmed.ncbi.nlm.nih.gov/19887545/

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 its methylcellulose solution? and how to prepare methylcellulose itself? Once make the solution, how should i keep it?

回答：
It is a suspension or emulsion in 0.5% methylcellulose, 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 methylcellulose solution of this compound 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