Home Cell Cycle Wee1 inhibitor Adavosertib (AZD1775, MK-1775)

연구용

Adavosertib (AZD1775, MK-1775) Wee1 inhibitor

제품 번호: S1525

Adavosertib (MK-1775, AZD1775) is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM in a cell-free assay; hinders G2 DNA damage checkpoint. Phase 2.
Adavosertib (AZD1775, MK-1775) Wee1 inhibitor Chemical Structure

화학 구조

분자량: 500.6

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품질 관리 (Quality Control)

배치: 순도: 99.99%
99.99

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
ASPC-1 Growth Inhibition Assay IC50=13.2 ± 1.1 μM 25458954
BxPC-3 Growth Inhibition Assay IC50=0.8 ± 0.03 μM 25458954
CFPAC-1 Growth Inhibition Assay IC50=3.3 ± 0.2 μM 25458954
HPAC Growth Inhibition Assay IC50=0.5 ± 0.01 μM 25458954
MIAPaCa-2 Growth Inhibition Assay IC50=0.5 ± 0.05 μM 25458954
PANC-1 Growth Inhibition Assay IC50=10.6 ± 1.1 μM 25458954
SK-N-BE (2) 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), MK→PAN Growth Inhibition Assay IC50=2.4 ± 0.3 μM 25308916
SK-N-AS Growth Inhibition Assay IC50=0.50 ± 0.02 μM 25308916
SK-N-DZ Growth Inhibition Assay IC50=0.36 ± 0.01 μM 25308916
SK-N-AS Apoptosis Assay 500 nM 48 h induces cell apoptosis 25308916
SK-N-DZ Apoptosis Assay 500 nM 48 h induces cell apoptosis 25308916
THP-1 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
U937 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
OCI-AML3 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
MOLM-13 Growth Inhibition Assay 125/250/500 nM 48 h increases cell death in a concentration-dependent manner 25084614
CMK Cell Viability Assay 10-10000 nM 72 h reduces cell vialibity in a concentration-dependent manner 24962331
CMY Cell Viability Assay 10-10000 nM 72 h reduces cell vialibity in a concentration-dependent manner 24962331
Dayo Growth Inhibition Assay IC50=150 nM 24661910
UW228 Growth Inhibition Assay IC50=232 nM 24661910
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
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
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 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
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
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
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
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 500.6 화학식

C27H32N8O2

 보관 (수령일로부터)
CAS 번호 955365-80-7 SDF 다운로드 원액 보관

동의어 AZD1775 Smiles CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (199.76 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

특징
The first reported Wee1 inhibitor.
Targets/IC50/Ki
Wee1
(Cell-free assay)
5.2 nM
시험관 내(In vitro)

Adavosertib (MK-1775) inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, it displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, this compound treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. Its treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas at 300 nM, sufficient to inhibit Wee1 by >80%, it displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells.

키나아제 분석
In vitro kinase assays
재조합 인간 Wee1이 사용됩니다. 키나아제 반응은 10 μM ATP, 1.0 μCi의 [γ-33P]ATP, 그리고 2.5 μg의 poly(Lys, Tyr)를 기질로 하여 증가하는 농도의 Adavosertib (MK-1775) 존재 하에 30°C에서 30분 동안 수행됩니다. 기질에 통합된 방사능은 MultiScreen-PH 플레이트에 포획되며 액체 섬광 계수기로 측정됩니다.
생체 내(In vivo)

Adavosertib (MK-1775) treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Its antitumor efficacy in the nude rat HeLa-luc and TOV21G-shp53 xenograft models is also moderate.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 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
S1525-WB1
25609063
Immunofluorescence tubulin / p-HH3(S10) γH2AX Cleaved caspase-3 / pH3
S1525-IF1
30755439
Growth inhibition assay Cell viability IC50
S1525-viability
25458954

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
How to prepare its methylcellulose solution? and how to prepare methylcellulose itself? Once make the solution, how should i keep it?

답변:
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.