Name: PF-477736
Brand: Selleck Chemicals
SKU: S2904
Rating: 5 (36 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.80%

99.80

Dianas relacionadas	CDK HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase
Otros Chk Inhibidores	Prexasertib (LY2606368) Dihydrochloride CCT245737 (SRA737) AZD7762 Rabusertib (LY2603618) MK-8776 (SCH 900776) CHIR-124 Prexasertib (LY2606368) BML-277 (Chk2 Inhibitor II) GDC-0575 SAR-020106

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

Líneas celulares	Tipo de ensayo	Descripción de la actividad	PMID
TC32	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
U-2 OS	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
A673	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
Saos-2	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
RD	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
SK-N-SH	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
OHS-50	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
SJ-GBM2	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	419.48	Fórmula	C₂₂H₂₅N₇O₂	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	952021-60-2	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	PF-736, PF-00477736			Smiles	CN1C=C(C=N1)C2=C3C=NNC(=O)C4=C3C(=CC(=C4)NC(=O)C(C5CCCCC5)N)N2

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 84 mg/mL (200.24 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.
Clear solution	5%DMSO 1 40%PEG300 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.	7.500mg/ml (17.88mM)	Taking the 1 mL working solution as an example, add 50 μL of 150 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. 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.
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.

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)

Targets/IC₅₀/Ki	Chk1 (Cell-free assay) 0.49 nM(Ki) VEGFR2 (Cell-free assay) 8 nM(Ki) Fms (Cell-free assay) 10 nM(Ki) YES (Cell-free assay) 14 nM(Ki) Chk2 (Cell-free assay) 47 nM(Ki)
In vitro	PF-477736 (128 nM) abrogates the camptothecin-induced DNA damage checkpoint in a dose-dependent manner in CA46 and HeLa cells. This compound effectively abrogates the -induced S-phase arrest with a corresponding increase in apoptotic cell populations in HT29 cells. This chemical (540 nM) enhances -induced cytotoxicity in a time- and dose-dependent manner in HT29 cells. It potentiates the growth-inhibitory activity of a panel of chemotherapeutic agents across a broad spectrum of p53-deficient human cancer cell lines in the MTT assay. Addition of this compound (360 nM) to -arrested cells induces a dramatic increase in the intensity of H2AX phosphorylation, reflecting a greater number of γ-H2AX molecules near sites of DNA damage. This chemical (0.5 nM) selectively blocks p73 and P53 phosphorylation in presence of curcumin in HL-60 cells. It (360 nM) suppresses -induced phosphorylation of histone H3 (Ser10) and Cdc25C (Ser216) and potentiates apoptosis in COLO205 cells. This compound (250 nM) combined with MK-1775 has marked synergistic cytotoxic activity in OVCAR-5 cells. It (250 nM) combined with MK-1775 causes accumulation of cells with a DNA content between 2N and 4N in OVCAR-5 cells. This chemical (250 nM) combined with MK-1775 causes premature mitosis before the end of DNA replication, with damaged DNA leading to apoptotic cell death in OVCAR-5 cells.
Ensayo de quinasa	Ensayo de unión
Ensayo de quinasa	El ensayo se realiza en una placa de 96 pocillos durante 20 minutos a 30℃ en 0,1 mL de tampón de ensayo que contiene 50 mM TRIS pH 7,5, 0,4 M NaCl, 4 mM PEP, 0,15 mM NADH, 28 unidades de lactato deshidrogenasa/mL, 16 unidades de piruvato quinasa/mL, 3 mM DTT, 0,125 mM Syntide-2, 0,15 mM ATP y 25 mM de cloruro de magnesio. Los ensayos se inician con 1 nM del dominio quinasa CHK1. La inhibición de la actividad de CHK1 se determina midiendo las velocidades iniciales en presencia de concentraciones variables de este compuesto. Los datos se analizan utilizando el software Enzyme Kinetic y Excel y se ajustan a un modelo cinético de inhibición competitiva para obtener un valor de Ki. La selectividad quinasa de este químico se evalúa mediante un cribado a 1 μM o 10 μM frente a un panel de aproximadamente 100 proteínas quinasas.
In vivo	PF-477736 (4 mg/kg i.v.) results in terminal half-life (T1/2) of 2.9 hours, AUC of 5.72 μg×hr/mL and CLp of 11.8 mL/min/kg in rats. This compound dose-dependently enhances the antitumor activity of a maximum tolerated dose in the Colo205 xenograft mouse model. This chemical (12 mg/kg) induces an increase in the phosphorylation of histone H3 (Ser10) and of phospho-histone H2AX in the Colo205 xenograft mouse model. This compound (15 mg/kg i.p.) enhances induced tumor growth inhibition and tumor growth delay in COLO205 and MDA-MB-231 xenograft models. This chemical (10 mg/kg once daily i.p.) combined with MK-1775 (30 mg/kg twice a day oral) leads to greater tumor growth inhibition in mice bearing OVCAR-5 xenografts.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/18723486/ [2] https://pubmed.ncbi.nlm.nih.gov/20675383/ [3] https://pubmed.ncbi.nlm.nih.gov/19584159/ [4] https://pubmed.ncbi.nlm.nih.gov/22713237/

Aplicaciones (Applications)

Métodos	Biomarcadores	PMID
Growth inhibition assay	Cell viability	29167438
Western blot	p-ATM / γ-H2AX p-53 / p-p53 / p21 / MDM2	31362335
Immunofluorescence	p-p53	31362335

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
NCT00437203	Terminated	Neoplasms	Pfizer	December 2006	Phase 1

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
Can you advise the vehicle suggested for S2904: 2% DMSO/40% PEG 300 at 5mg/ml, is it a suspension or clear solution? I wanted to know how to dissolve it for an i.p. injection in mice.

Respuesta:
It can dissolve in 2% DMSO/40% PEG 300 at 5mg/ml as a clear solution. If you are going to use this kind of vehicle, please dissolve this compound in DMSO clearly first, then add PEG300, then water.

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):

PF-477736 Chk inhibitor

Estructura química

Peso molecular: 419.48

Control de calidad (Quality Control)

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

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

PF-477736 Chk inhibitor

Estructura química

Peso molecular: 419.48

Control de calidad (Quality Control)

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

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

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