Adavosertib (MK-1775)

別名: AZD1775

目錄號：S1525 Purity: 99.99%

Adavosertib (MK-1775, AZD1775)是一種有效的，高選擇性Wee1抑制劑，無細胞試驗中IC50為5.2 nM；阻礙G2期DNA損傷檢驗點。Phase 2。

Adavosertib (MK-1775) Chemical Structure

CAS: 955365-80-7

規(guī)格	價格	庫存
10mM (1mL in DMSO)	794.43	現(xiàn)貨
5mg	647.01	現(xiàn)貨
10mg	1040.13	現(xiàn)貨
25mg	1941.03	現(xiàn)貨
100mg	4823.91	現(xiàn)貨
1g	10401.3	現(xiàn)貨
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400-668-6834 info@selleck.cn

產(chǎn)品質(zhì)控

批次：純度： 99.99%

99.99

Adavosertib (MK-1775)相關產(chǎn)品

相關產(chǎn)品	PD0166285	點擊展開
相關化合物庫	激酶抑制劑庫 PI3K/Akt 抑制劑庫 MAPK抑制劑庫 DNA損傷/ DNA修復化合物庫細胞周期化合物庫	點擊展開

細胞實驗數(shù)據(jù)示例

細胞系	實驗類型	給藥濃度	孵育時間	活性描述	文獻信息
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
點擊查看更多細胞系數(shù)據(jù)

生物活性

產(chǎn)品描述

Adavosertib (MK-1775, AZD1775)是一種有效的，高選擇性Wee1抑制劑，無細胞試驗中IC50為5.2 nM；阻礙G2期DNA損傷檢驗點。Phase 2。

特性

首個報道的 Wee1抑制劑。

靶點

Wee1 ^[1]
(Cell-free assay)

5.2 nM

體外研究(In Vitro)
體外研究活性	MK-1775以ATP競爭的方式抑制Wee1激酶。與作用于Wee1相比，MK-1775對Yes的效能低2-到3-倍，IC50為14 nM，對7種其他激酶的效能低10倍，1 μM濃度下抑制率>80%，比對人Myt 1選擇性高100倍以上，并抑制周期蛋白依賴性激酶1 (CDC2) 在可選擇位點(Thr14) 的磷酸化作用。通過阻斷負荷突變型p53的WiDr細胞中Wee1活性，廢止DNA損傷檢控點，MK-1775治療抑制Tyr15 (CDC2Y15)位點的CDC2基礎磷酸化作用，EC50為49 nM，并劑量依賴性抑制誘導的CDC2磷酸化和細胞周期阻滯，EC50分別為82 nM和81 nM，180 nM 和163 nM，以及159 nM 和 160 nM。30-100 nM 的MK-1775單獨治療在WiDr 和 H1299細胞中沒有顯著的抗增殖作用，而300 nM的MK-1775足以抑制>80%的Wee1，表現(xiàn)出溫和但顯著的抗增殖作用，在WiDr和H1299細胞中抑制率分別為34.1%和28.4%。^[1]
激酶實驗	體外激酶試驗
激酶實驗	使用重組人Wee1。激酶反應使用10 μM ATP，1.0 μCi of [γ-³³P]ATP，和2.5 μg poly(Lys, Tyr)作為底物，在逐漸增加濃度的MK-1775存在下，在30°C環(huán)境中進行30分鐘。整合到底物的放射性被捕獲到MultiScreen-PH平板，在液體閃爍計數(shù)器上計數(shù)。
細胞實驗	細胞系	WiDr，NCI-H1299，TOV21G，和 HeLa細胞
	濃度	在DMSO中溶解，終濃度為~10 μM
	孵育時間	24小時
	方法	細胞處理24小時，然后用MK-1775再處理24小時。細胞活性使用SpectraMax通過WST-8試劑盒測定。細胞內(nèi)caspase-3/7活性使用Caspase-3/7 Glo試劑盒測定。
實驗圖片	檢測方法	檢測指標	實驗圖片	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

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	MK-1775(~20 mg/kg)單獨治療對WiDr異種移植物表現(xiàn)出最小的抗腫瘤作用，在大鼠體內(nèi)第3天時T/C為69%。在裸鼠HeLa-luc和TOV21G-shp53異種移植模型中，MK-1775單獨的抗腫瘤效能是溫和的。^[1]
動物實驗	Animal Models	負荷WiDr，HeLa-luc，或TOV21G-shp53腫瘤的免疫缺陷裸鼠(F344/NJcl-rnu)
	Dosages	~20 mg/kg/day
	Administration	口服

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗信息 (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

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

參考文獻

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

化學信息&溶解度

分子量	500.6	分子式	C₂₇H₃₂N₈O₂
CAS號	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
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復凍融！	1年-80°C溶于溶劑
儲存條件(自收到貨起)	3年-20°C粉狀	儲備液保存和期限建議分裝儲備液，避免反復凍融！	1個月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 100 mg/mL ( (199.76 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL ( (199.76 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Ethanol : 10 mg/mL (19.97 mM)

Water : Insoluble

DMSO : 100 mg/mL ( (199.76 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 100 mg/mL ( (199.76 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計算器

體內(nèi)溶解度批次：現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑					動物體內(nèi)配方計算器
體內(nèi)溶解度批次：現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑	澄清溶液	5%DMSO 1 95% Corn oil	6.0mg/ml (11.99mM)	以 1 mL 工作液為例，取 50 μL 120 mg/mL 的澄清 DMSO 儲備液加到 950 μL玉米油中，混合均勻。工作液請現(xiàn)配現(xiàn)用！	動物體內(nèi)配方計算器
澄清溶液	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O	12.0mg/ml (23.97mM)	以 1 mL 工作液為例，取 50 μL 240 mg/mL 的澄清 DMSO 儲備液加到 400 μL PEG300 中，混合均勻使其澄清；向上述體系中加入50 μL Tween-80，混合均勻使其澄清；然后繼續(xù)加入 500 μLddH2O定容至 1 mL。工作液請現(xiàn)配現(xiàn)用！
澄清溶液	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O	5.0mg/ml (9.99mM)	以 1 mL 工作液為例，取 50 μL 100 mg/mL 的澄清 DMSO 儲備液加到 400 μL PEG300 中，混合均勻使其澄清；向上述體系中加入50 μL Tween-80，混合均勻使其澄清；然后繼續(xù)加入 500 μLddH2O定容至 1 mL。工作液請現(xiàn)配現(xiàn)用！

實驗計算

摩爾濃度計算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計算器分子量計算器

動物體內(nèi)配方計算器（澄清溶液）

第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）

給藥劑量 mg/kg 動物平均體重 g 每只動物給藥體積 μL 動物數(shù)量只

第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH₂O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

技術支持

在訂購、運輸、儲存和使用我們的產(chǎn)品的任何階段，您遇到的任何問題，均可以通過撥打我們的熱線電話400-668-6834，或者技術支持郵箱tech@selleck.cn，直接聯(lián)系到我們。我們會在24小時內(nèi)盡快聯(lián)系您。

操作手冊

如果有其他問題，請給我們留言。

* 必填項

常見問題及建議解決方法

問題 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):

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Adavosertib (MK-1775)

產(chǎn)品質(zhì)控

Adavosertib (MK-1775)相關產(chǎn)品

相關信號通路圖

細胞實驗數(shù)據(jù)示例

生物活性

化學信息&溶解度

實驗計算

技術支持

常見問題及建議解決方法