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Adavosertib (AZD1775, MK-1775) Wee1 inhibitor

Name: Adavosertib (AZD1775, MK-1775)
Brand: Selleck Chemicals
SKU: S1525
Rating: 5 (241 reviews)

Cat. No.: 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

Estructura química

Peso molecular: 500.6

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.99%

99.99

Dianas relacionadas	CDK HSP PD-1/PD-L1 ROCK DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase Casein Kinase
Otros Wee1 Inhibidores	PD0166285 Zedoresertib (Debio-0123, WEE1-IN-5) Azenosertib (Zn-C3) Potrasertib BMS-986463

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	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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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	500.6	Fórmula	C₂₇H₃₂N₈O₂	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	955365-80-7	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	AZD1775			Smiles	CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 100 mg/mL (199.76 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	12.000mg/ml (23.97mM)	Taking the 1 mL working solution as an example, add 50 μL of 240 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 95% Corn oil Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	6.000mg/ml (11.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 120 mg/mL clarified DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	5.000mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Características	The first reported Wee1 inhibitor.
Targets/IC₅₀/Ki	Wee1 (Cell-free assay) 5.2 nM
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.
Ensayo de quinasa	Ensayos de quinasa in vitro
Ensayo de quinasa	Se utiliza Wee1 humana recombinante. La reacción de la quinasa se lleva a cabo con 10 μM de ATP, 1,0 μCi de [γ-³³P]ATP y 2,5 μg de poli(Lys, Tyr) como sustrato en presencia de concentraciones crecientes de Adavosertib (MK-1775) a 30°C durante 30 minutos. La radioactividad incorporada en el sustrato se retiene en placas MultiScreen-PH y se cuenta en un contador de centelleo líquido.
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.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/19887545/

Aplicaciones (Applications)

Métodos	Biomarcadores	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

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
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

Preguntas frecuentes (Frequently Asked Questions)

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

Respuesta:
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):