Name: PHA-665752
Brand: Selleck Chemicals
SKU: S1070
Rating: 5 (97 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.91%

99.91

Dianas relacionadas	EGFR VEGFR FGFR PDGFR Src MEK CSF-1R HER2 FLT3 c-Kit
Otros c-Met Inhibidores	Tepotinib (EMD-1214063) Dihexa SGX-523 Foretinib (GSK1363089, XL880) SU11274 BMS-777607 JNJ-38877605 Tivantinib PF-04217903 Savolitinib (AZD6094)

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

Líneas celulares	Tipo de ensayo	Descripción de la actividad
NCI-SNU-5	Growth Inhibition Assay	IC50=0.12375 μM
LB2241-RCC	Growth Inhibition Assay	IC50=0.15702 μM
KINGS-1	Growth Inhibition Assay	IC50=0.35911 μM
ALL-PO	Growth Inhibition Assay	IC50=0.81277 μM
SK-LMS-1	Growth Inhibition Assay	IC50=0.89846 μM
MV-4-11	Growth Inhibition Assay	IC50=1.2947 μM
SUP-T1	Growth Inhibition Assay	IC50=2.13964 μM
MRK-nu-1	Growth Inhibition Assay	IC50=2.40056 μM
ES1	Growth Inhibition Assay	IC50=3.34866 μM
NOS-1	Growth Inhibition Assay	IC50=4.39867 μM
KM12	Growth Inhibition Assay	IC50=4.418 μM
Becker	Growth Inhibition Assay	IC50=5.2466 μM
NCI-SNU-1	Growth Inhibition Assay	IC50=5.63733 μM
EW-22	Growth Inhibition Assay	IC50=7.73614 μM
ES6	Growth Inhibition Assay	IC50=7.8195 μM
A498	Growth Inhibition Assay	IC50=8.28446 μM
EW-16	Growth Inhibition Assay	IC50=9.6543 μM
CTV-1	Growth Inhibition Assay	IC50=9.85024 μM
ETK-1	Growth Inhibition Assay	IC50=10.2931 μM
NCI-H1395	Growth Inhibition Assay	IC50=10.8024 μM
DOHH-2	Growth Inhibition Assay	IC50=10.9264 μM
GI-1	Growth Inhibition Assay	IC50=11.8596 μM
HT-144	Growth Inhibition Assay	IC50=14.2163 μM
ES5	Growth Inhibition Assay	IC50=14.467 μM
NALM-6	Growth Inhibition Assay	IC50=15.2196 μM
KNS-81-FD	Growth Inhibition Assay	IC50=15.5849 μM
TE-15	Growth Inhibition Assay	IC50=16.5771 μM
SCC-15	Growth Inhibition Assay	IC50=18.3498 μM
EoL-1-cell	Growth Inhibition Assay	IC50=18.4545 μM
NCI-H720	Growth Inhibition Assay	IC50=18.771 μM
NB14	Growth Inhibition Assay	IC50=19.5425 μM
KE-37	Growth Inhibition Assay	IC50=19.8233 μM
LXF-289	Growth Inhibition Assay	IC50=19.8629 μM
RPMI-8402	Growth Inhibition Assay	IC50=20.3269 μM
SK-N-DZ	Growth Inhibition Assay	IC50=21.2131 μM
ACN	Growth Inhibition Assay	IC50=22.2497 μM
TE-11	Growth Inhibition Assay	IC50=26.069 μM
COLO-800	Growth Inhibition Assay	IC50=27.17 μM
MOLT-13	Growth Inhibition Assay	IC50=27.1847 μM
697	Growth Inhibition Assay	IC50=28.7633 μM
VA-ES-BJ	Growth Inhibition Assay	IC50=29.3729 μM
EW-13	Growth Inhibition Assay	IC50=29.5045 μM
NB7	Growth Inhibition Assay	IC50=32.2665 μM
MONO-MAC-6	Growth Inhibition Assay	IC50=32.8795 μM
SW962	Growth Inhibition Assay	IC50=33.4513 μM
KS-1	Growth Inhibition Assay	IC50=33.9481 μM
KU812	Growth Inhibition Assay	IC50=34.5702 μM
IMR-5	Growth Inhibition Assay	IC50=37.4318 μM
BC-1	Growth Inhibition Assay	IC50=38.033 μM
NCI-H510A	Growth Inhibition Assay	IC50=38.2032 μM
EW-18	Growth Inhibition Assay	IC50=40.8303 μM
CCRF-CEM	Growth Inhibition Assay	IC50=42.2797 μM
HH	Growth Inhibition Assay	IC50=43.5069 μM
NCI-H2171	Growth Inhibition Assay	IC50=46.0272 μM
LC-2-ad	Growth Inhibition Assay	IC50=49.1413 μM
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	641.61	Fórmula	C₃₂H₃₄Cl₂N₄O₄S	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	477575-56-7	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	CC1=C(NC(=C1C(=O)N2CCCC2CN3CCCC3)C)C=C4C5=C(C=CC(=C5)S(=O)(=O)CC6=C(C=CC=C6Cl)Cl)NC4=O

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 128 mg/mL (199.49 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 10 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.
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 95% corn oil Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	0.460mg/ml (0.72mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 9.2 mg/ml to 950 μL of corn oil, mix evenly to clarify it, and prepare the working solution for immediate use!
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	c-Met (Cell-free assay) 9 nM RON (Cell-free assay) 68 nM Flk1 (Cell-free assay) 200 nM
In vitro	PHA-665752 significantly inhibits c-Met kinase activity with K_i of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. This compound potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. It also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, this chemical potently inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines. It inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of <60 nM, and inhibits constitutive cell motility and migration by 92.5% at 0.2 μM. Inhibition of c-Met by this compound (0.2 μM) also induces cell apoptosis of 33.1% and G1 cell cycle arrest with cells in G1 phase increasing from 42.4% to 77.0%. It can cooperate with rapamycin to inhibit cell growth of TPR-MET-transformed BaF3 cells and non-small cell lung cancer H441 cells.
Ensayo de quinasa	Ensayo enzimático in vitro
Ensayo de quinasa	La proteína de fusión GST del dominio quinasa c-Met se utiliza para el ensayo de c-Met. El valor de IC50 de PHA-665752 para la inhibición de c-Met se basa en la fosforilación de sustratos peptídicos quinasas o poli-glu-tyr en presencia de ATP y un catión divalente (MgCl₂ o MnCl₂ 10-20 mM). El rango lineal (es decir, el período de tiempo durante el cual la tasa permanece equivalente a la tasa inicial) se determina para c-Met, y la medición cinética y la determinación de la IC50 se realizan dentro de este rango.
In vivo	Administration of PHA-665752 induces a dose-dependent tumor growth inhibition of S114 xenografts by 20 %, 39% and 68%, at dose of 7.5, 15, and 30 mg/kg/day, respectively. This compound treatment significantly reduces the tumor growth of NCI-H69, NCI-H441 and A549 in mouse xenografts by 99%, 75%, and 59%, respectively. It also significantly inhibits angiogenesis by >85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/14612533/ [2] https://pubmed.ncbi.nlm.nih.gov/15788682/ [3] https://pubmed.ncbi.nlm.nih.gov/17440059/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	IDO p-Met / Met / p-Akt / Akt / p-ERK / ERK		27082119
Growth inhibition assay	Cell proliferation		20603611

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
I need to use it for intraperitoneal application in mice. Could you tell me the solvent you use, please?

Respuesta:
The highest concentration of this compound (S1070) in 4% DMSO+30% PEG 300+5% Tween 80+ddH2O is 5mg/ml. If you want to get higher concentration, the concentration of DMSO and PEG will be higher. For example, it can be dissolved in 8% DMSO+50% PEG 300+5% Tween 80+ddH2O at 10mg/ml clearly.

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):

PHA-665752 c-Met inhibitor

Estructura química

Peso molecular: 641.61

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)

Preguntas frecuentes (Frequently Asked Questions)

PHA-665752 c-Met inhibitor

Estructura química

Peso molecular: 641.61

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)

Preguntas frecuentes (Frequently Asked Questions)

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