Name: PF-3758309
Brand: Selleck Chemicals
SKU: S7094
Rating: 5 (29 reviews)

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Control de calidad

Lote: Pureza: 99.98%

99.98

Dianas relacionadas	Akt Wnt/beta-catenin PKC HSP ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK
Otros PAK Inhibidores	IPA-3 FRAX597 FRAX486 FRAX1036 LCH-7749944 NVS-PAK1-1 Hydrastine GNE 2861 G-5555

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad	PMID
human MDA-MB-436 cells	Cytotoxic assay	24-48 h	Cytotoxicity against human MDA-MB-436 cells assessed as reduction in cell viability after 24 to 48 hrs by Celltiter-glo luminescence assay, IC50=0.79 nM	24432870
HCT116	Antiproliferative activity against	72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by CCK8 assay, IC50=0.039μM.	29886323
A549	Antiproliferative activity against	72 hrs	Antiproliferative activity against human A549 cells after 72 hrs by CCK8 assay, IC50=0.463μM.	29886323
TC32	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
fibroblast cells	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	29435139
Rh41	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
A673	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
BT-12	qHTS of pediatric cancer cell lines to identify multiple opportunities for		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
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Información química, almacenamiento y estabilidad

Peso molecular	490.62	Fórmula	C₂₅H₃₀N₈OS	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	898044-15-0	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	PF-03758309			Smiles	CC1=NC2=C(C(=N1)NC3=NNC4=C3CN(C4(C)C)C(=O)NC(CN(C)C)C5=CC=CC=C5)SC=C2

Solubilidad

In vitro
Lote:

DMSO : 98 mg/mL (199.74 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 98 mg/mL

Water : 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.	5.000mg/ml (10.19mM)	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 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.
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.	5.000mg/ml (10.19mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear 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.

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

Características	PF-3758309 is potent toward a broad array of tumor cell lines from different tumor types.
Targets/IC₅₀/Ki	PAK1 (Cell-free assay) 13.7 nM(Ki) PAK6 (Cell-free assay) 17.1 nM(Ki) PAK5 (Cell-free assay) 18.1 nM(Ki) PAK4 (Cell-free assay) 18.7 nM(Ki) PAK3 (Cell-free assay) 99 nM PAK2 (Cell-free assay) 190 nM
In vitro	PF-3758309 es un potente (K_d = 2,7 nM), inhibidor de PAK4 competitivo con ATP, con un K_i de 18,7 nM. En las células, este compuesto inhibe la fosforilación del sustrato de PAK4 GEF-H1 (IC50 = 1,3 nM) y el crecimiento independiente del anclaje de un panel de líneas celulares tumorales (IC50 = 4,7 nM). También inhibe la acumulación endógena de pGEF-H1 en células HCT116. Este químico inhibe potentemente la proliferación celular (IC50 = 20 nM) y el crecimiento independiente del anclaje (IC50 = 27 nM) de células A549.
Ensayo de quinasa	Ensayo celular de Fosfo-GEF-H1
Ensayo de quinasa	Las células TR-293-KDG se construyen a partir de células HEK293 transfectadas de forma estable con el dominio cinasa de PAK4 inducible por tetraciclina (aminoácidos 291-591) y GEFH1ΔDH marcado con HA expresado constitutivamente (aminoácidos 210-921). Las células TR-293-KDG se incuban durante 3 h con PF-3758309, se capturan en una placa recubierta con anticuerpo anti-HA, se detectan con un anticuerpo anti-fosfo-S810-GEF-H1 y se cuantifican con un conjugado de anticuerpo de peroxidasa de rábano picante-cabra anti-conejo.
In vivo	PF-3758309 bloquea el crecimiento de múltiples xenoinjertos de tumores humanos, con un valor de EC50 plasmático de 0,4 nM en el modelo más sensible. Este compuesto es antiproliferativo e induce apoptosis en un modelo tumoral HCT116.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/20439741/

Aplicaciones

Métodos	Biomarcadores	Imágenes	PMID
Western blot	PAK4 / PI3K / p-AKT / AKT / p-mTOR / mTOR		28407679

Soporte técnico

Instrucciones de manipulación

Tel: +1-832-582-8158 Ext:3

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Preguntas frecuentes

Pregunta 1:
If this compound crosses the blood brain barrier?

Respuesta:
We're sorry we don't have any data on whether it can cross BBB or not, the following reference indicate that this compound can not: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490962/.

C1=C0/X	C1:	LOG(C1):
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C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):

PF-3758309 PAK inhibidor

Estructura química

Peso molecular: 490.62