Home MAPK Raf inhibidor PLX-4720

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PLX-4720 Inhibidor de B-Raf

Cat. No.S1152

PLX4720 es un inhibidor potente y selectivo de B-RafV600E con una IC50 de 13 nM en un ensayo sin células, igualmente potente que c-Raf-1 (mutaciones Y340D y Y341D), con una selectividad 10 veces mayor para B-RafV600E que para B-Raf de tipo salvaje.
PLX-4720 Raf inhibidor Chemical Structure

Estructura química

Peso molecular: 413.83

Saltar a

Control de calidad

Lote: Pureza: 99.98%
99.98

Productos que se suelen utilizar junto con PLX-4720

Dactolisib (BEZ235)

Treatment with this compound and Dactolisib decreases both pERK and pAKT levels in Colo-205 xenografts.

Navitoclax (ABT-263)

It and Navitoclax can enhance the clinical efficacy of BRAF inhibitors.

NMS-E973

It and NMS-E973 show a synergic antiproliferative activity in A375 melanoma cells.

SB431542

Cotreatment with this compound and SB431542 abolish the increase in cell growth caused by low-dose PLX-4720 in Colo829 and A375(M2) cells.

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares Tipo de ensayo Concentración Tiempo de incubación Formulación Descripción de la actividad PMID
DU-4475 Growth Inhibition Assay IC50=0.07457 μM SANGER
EoL-1-cell Growth Inhibition Assay IC50=0.14166 μM SANGER
C32 Growth Inhibition Assay IC50=0.15131 μM SANGER
M14 Growth Inhibition Assay IC50=0.21757 μM SANGER
CP50-MEL-B Growth Inhibition Assay IC50=0.29784 μM SANGER
A101D Growth Inhibition Assay IC50=0.32589 μM SANGER
G-361 Growth Inhibition Assay IC50=0.34637 μM SANGER
HT-144 Growth Inhibition Assay IC50=0.36329 μM SANGER
ACN Growth Inhibition Assay IC50=0.38477 μM SANGER
COLO-829 Growth Inhibition Assay IC50=0.38968 μM SANGER
MEL-HO Growth Inhibition Assay IC50=0.41179 μM SANGER
SH-4 Growth Inhibition Assay IC50=0.41422 μM SANGER
SK-MEL-3 Growth Inhibition Assay IC50=0.51568 μM SANGER
A375 Growth Inhibition Assay IC50=0.67359 μM SANGER
MMAC-SF Growth Inhibition Assay IC50=0.68614 μM SANGER
BHT-101 Growth Inhibition Assay IC50=0.70702 μM SANGER
K5 Growth Inhibition Assay IC50=0.76148 μM SANGER
BV-173 Growth Inhibition Assay IC50=0.79644 μM SANGER
RVH-421 Growth Inhibition Assay IC50=0.86796 μM SANGER
HCC2218 Growth Inhibition Assay IC50=0.87844 μM SANGER
WM-115 Growth Inhibition Assay IC50=0.88692 μM SANGER
SK-MEL-28 Growth Inhibition Assay IC50=1.04569 μM SANGER
COLO-679 Growth Inhibition Assay IC50=1.10464 μM SANGER
MZ7-mel Growth Inhibition Assay IC50=1.14963 μM SANGER
SK-MEL-30 Growth Inhibition Assay IC50=1.33386 μM SANGER
NCI-H209 Growth Inhibition Assay IC50=1.6086 μM SANGER
HTC-C3 Growth Inhibition Assay IC50=1.66294 μM SANGER
KARPAS-45 Growth Inhibition Assay IC50=2.04978 μM SANGER
NCI-SNU-5 Growth Inhibition Assay IC50=2.11969 μM SANGER
KP-4 Growth Inhibition Assay IC50=2.30787 μM SANGER
PA-1 Growth Inhibition Assay IC50=2.72673 μM SANGER
HuO-3N1 Growth Inhibition Assay IC50=2.87946 μM SANGER
NCI-H358 Growth Inhibition Assay IC50=2.92232 μM SANGER
CTB-1 Growth Inhibition Assay IC50=3.40176 μM SANGER
697 Growth Inhibition Assay IC50=3.55266 μM SANGER
CP66-MEL Growth Inhibition Assay IC50=4.15927 μM SANGER
NB13 Growth Inhibition Assay IC50=4.49179 μM SANGER
DBTRG-05MG Growth Inhibition Assay IC50=4.53325 μM SANGER
A2058 Growth Inhibition Assay IC50=4.72164 μM SANGER
KG-1 Growth Inhibition Assay IC50=4.73908 μM SANGER
8305C Growth Inhibition Assay IC50=5.1873 μM SANGER
RPMI-7951 Growth Inhibition Assay IC50=5.80283 μM SANGER
CHL-1 Growth Inhibition Assay IC50=5.97603 μM SANGER
TI-73 Growth Inhibition Assay IC50=6.00902 μM SANGER
HT-1080 Growth Inhibition Assay IC50=6.10946 μM SANGER
ES5 Growth Inhibition Assay IC50=6.14924 μM SANGER
8-MG-BA Growth Inhibition Assay IC50=6.18129 μM SANGER
NB7 Growth Inhibition Assay IC50=6.21373 μM SANGER
H4 Growth Inhibition Assay IC50=6.22493 μM SANGER
CAL-72 Growth Inhibition Assay IC50=6.45423 μM SANGER
HCC1806 Growth Inhibition Assay IC50=6.81931 μM SANGER
BCPAP Growth Inhibition Assay IC50=7.21764 μM SANGER
LB2241-RCC Growth Inhibition Assay IC50=7.36907 μM SANGER
COLO-741 Growth Inhibition Assay IC50=8.01679 μM SANGER
HSC-3 Growth Inhibition Assay IC50=8.07068 μM SANGER
SW982 Growth Inhibition Assay IC50=8.41516 μM SANGER
GCT Growth Inhibition Assay IC50=8.75314 μM SANGER
KY821 Growth Inhibition Assay IC50=9.05178 μM SANGER
JVM-3 Growth Inhibition Assay IC50=9.56999 μM SANGER
RS4-11 Growth Inhibition Assay IC50=9.6048 μM SANGER
VA-ES-BJ Growth Inhibition Assay IC50=10.0149 μM SANGER
A431 Growth Inhibition Assay IC50=10.4212 μM SANGER
LXF-289 Growth Inhibition Assay IC50=10.458 μM SANGER
SK-MEL-24 Growth Inhibition Assay IC50=10.8274 μM SANGER
NOS-1 Growth Inhibition Assay IC50=10.8472 μM SANGER
KNS-62 Growth Inhibition Assay IC50=11.2404 μM SANGER
SK-HEP-1 Growth Inhibition Assay IC50=11.3527 μM SANGER
A3-KAW Growth Inhibition Assay IC50=11.7178 μM SANGER
SK-LU-1 Growth Inhibition Assay IC50=12.2655 μM SANGER
TYK-nu Growth Inhibition Assay IC50=12.3932 μM SANGER
NMC-G1 Growth Inhibition Assay IC50=12.6062 μM SANGER
BB65-RCC Growth Inhibition Assay IC50=12.7169 μM SANGER
QIMR-WIL Growth Inhibition Assay IC50=12.8833 μM SANGER
D-566MG Growth Inhibition Assay IC50=13.9576 μM SANGER
KYSE-140 Growth Inhibition Assay IC50=14.0753 μM SANGER
SCC-4 Growth Inhibition Assay IC50=14.3359 μM SANGER
U251 Growth Inhibition Assay IC50=14.8492 μM SANGER
D-542MG Growth Inhibition Assay IC50=14.9222 μM SANGER
LAMA-84 Growth Inhibition Assay IC50=14.9932 μM SANGER
NCI-H720 Growth Inhibition Assay IC50=15.2684 μM SANGER
DEL Growth Inhibition Assay IC50=15.4293 μM SANGER
SBC-1 Growth Inhibition Assay IC50=15.4305 μM SANGER
ECC10 Growth Inhibition Assay IC50=15.4458 μM SANGER
Daoy Growth Inhibition Assay IC50=15.7616 μM SANGER
SCH Growth Inhibition Assay IC50=15.7835 μM SANGER
MZ2-MEL Growth Inhibition Assay IC50=16.0646 μM SANGER
CAL-12T Growth Inhibition Assay IC50=16.4862 μM SANGER
KE-37 Growth Inhibition Assay IC50=16.8107 μM SANGER
LS-411N Growth Inhibition Assay IC50=17.118 μM SANGER
NCI-H2228 Growth Inhibition Assay IC50=17.3071 μM SANGER
SK-MEL-2 Growth Inhibition Assay IC50=17.4965 μM SANGER
HN Growth Inhibition Assay IC50=17.7248 μM SANGER
NCI-H1648 Growth Inhibition Assay IC50=17.818 μM SANGER
IA-LM Growth Inhibition Assay IC50=18.3172 μM SANGER
EW-13 Growth Inhibition Assay IC50=18.5708 μM SANGER
YKG-1 Growth Inhibition Assay IC50=19.5711 μM SANGER
KNS-81-FD Growth Inhibition Assay IC50=19.5858 μM SANGER
23132-87 Growth Inhibition Assay IC50=19.7642 μM SANGER
NUGC-3 Growth Inhibition Assay IC50=19.9887 μM SANGER
5637 Growth Inhibition Assay IC50=20.0478 μM SANGER
NCI-H1755 Growth Inhibition Assay IC50=20.4764 μM SANGER
RH-18 Growth Inhibition Assay IC50=20.5748 μM SANGER
RXF393 Growth Inhibition Assay IC50=20.6756 μM SANGER
LU-134-A Growth Inhibition Assay IC50=20.7056 μM SANGER
TE-12 Growth Inhibition Assay IC50=20.7201 μM SANGER
MOLT-4 Growth Inhibition Assay IC50=21.1915 μM SANGER
IGR-1 Growth Inhibition Assay IC50=21.3796 μM SANGER
HOP-92 Growth Inhibition Assay IC50=21.4987 μM SANGER
SK-MES-1 Growth Inhibition Assay IC50=21.7381 μM SANGER
LU-65 Growth Inhibition Assay IC50=21.8624 μM SANGER
MS-1 Growth Inhibition Assay IC50=22.1203 μM SANGER
LoVo Growth Inhibition Assay IC50=22.244 μM SANGER
A704 Growth Inhibition Assay IC50=22.5155 μM SANGER
HT-1376 Growth Inhibition Assay IC50=22.6059 μM SANGER
IST-MEL1 Growth Inhibition Assay IC50=22.6751 μM SANGER
Ramos-2G6-4C10 Growth Inhibition Assay IC50=22.7366 μM SANGER
T47D Growth Inhibition Assay IC50=22.7979 μM SANGER
HT-1197 Growth Inhibition Assay IC50=23.0817 μM SANGER
LB2518-MEL Growth Inhibition Assay IC50=23.6412 μM SANGER
J-RT3-T3-5 Growth Inhibition Assay IC50=24.7595 μM SANGER
SK-NEP-1 Growth Inhibition Assay IC50=24.8744 μM SANGER
NCI-H526 Growth Inhibition Assay IC50=25.0023 μM SANGER
IST-SL1 Growth Inhibition Assay IC50=25.2751 μM SANGER
HH Growth Inhibition Assay IC50=25.3192 μM SANGER
NCI-H82 Growth Inhibition Assay IC50=25.938 μM SANGER
SNU-449 Growth Inhibition Assay IC50=27.2018 μM SANGER
COR-L23 Growth Inhibition Assay IC50=27.2813 μM SANGER
LOXIMVI Growth Inhibition Assay IC50=27.368 μM SANGER
GR-ST Growth Inhibition Assay IC50=27.6706 μM SANGER
NCI-SNU-1 Growth Inhibition Assay IC50=27.944 μM SANGER
ALL-PO Growth Inhibition Assay IC50=28.1604 μM SANGER
ML-2 Growth Inhibition Assay IC50=28.2814 μM SANGER
HOP-62 Growth Inhibition Assay IC50=28.713 μM SANGER
EGI-1 Growth Inhibition Assay IC50=28.8845 μM SANGER
TCCSUP Growth Inhibition Assay IC50=28.9272 μM SANGER
LB996-RCC Growth Inhibition Assay IC50=29.5682 μM SANGER
LCLC-97TM1 Growth Inhibition Assay IC50=32.1964 μM SANGER
NCI-H1304 Growth Inhibition Assay IC50=32.3301 μM SANGER
KP-N-YS Growth Inhibition Assay IC50=32.5973 μM SANGER
NCI-H1770 Growth Inhibition Assay IC50=33.1648 μM SANGER
EM-2 Growth Inhibition Assay IC50=33.6504 μM SANGER
ChaGo-K-1 Growth Inhibition Assay IC50=33.7236 μM SANGER
ACHN Growth Inhibition Assay IC50=33.8385 μM SANGER
MN-60 Growth Inhibition Assay IC50=33.8544 μM SANGER
EW-18 Growth Inhibition Assay IC50=33.8971 μM SANGER
KGN Growth Inhibition Assay IC50=35.7292 μM SANGER
U031 Growth Inhibition Assay IC50=35.8132 μM SANGER
HMV-II Growth Inhibition Assay IC50=36.0774 μM SANGER
L-363 Growth Inhibition Assay IC50=37.6455 μM SANGER
NCI-H1155 Growth Inhibition Assay IC50=38.0015 μM SANGER
NCI-H1793 Growth Inhibition Assay IC50=38.1026 μM SANGER
P30-OHK Growth Inhibition Assay IC50=38.1332 μM SANGER
AN3-CA Growth Inhibition Assay IC50=38.1615 μM SANGER
UACC-257 Growth Inhibition Assay IC50=38.79 μM SANGER
MCF7 Growth Inhibition Assay IC50=39.8629 μM SANGER
KP-N-YN Growth Inhibition Assay IC50=40.4285 μM SANGER
T98G Growth Inhibition Assay IC50=40.4957 μM SANGER
HGC-27 Growth Inhibition Assay IC50=43.274 μM SANGER
NCI-H1092 Growth Inhibition Assay IC50=43.2895 μM SANGER
KARPAS-299 Growth Inhibition Assay IC50=43.3071 μM SANGER
LB1047-RCC Growth Inhibition Assay IC50=44.9959 μM SANGER
786-0 Growth Inhibition Assay IC50=45.65 μM SANGER
HCC2157 Growth Inhibition Assay IC50=46.0359 μM SANGER
NY Growth Inhibition Assay IC50=46.1778 μM SANGER
EFM-19 Growth Inhibition Assay IC50=46.7533 μM SANGER
EW-16 Growth Inhibition Assay IC50=46.7806 μM SANGER
UM-UC-3 Growth Inhibition Assay IC50=46.8059 μM SANGER
HT-29 Growth Inhibition Assay IC50=47.8792 μM SANGER
LN-405 Growth Inhibition Assay IC50=48.0827 μM SANGER
NCI-H727 Growth Inhibition Assay IC50=48.7726 μM SANGER
D-502MG Growth Inhibition Assay IC50=48.9676 μM SANGER
GMS-10 Growth Inhibition Assay IC50=49.2974 μM SANGER
MEL-JUSO Growth Inhibition Assay IC50=49.347 μM SANGER
insect cells Function assay Inhibition of N-terminal His-tagged BRAF V600E mutant (unknown origin) expressed in baculovirus infected insect cells co-expressing CDC37 using biotinylated-MEK as substrate by AlphaScreen assay, IC50 = 0.013 μM. 29461827
A375 Function assay Inhibition of BRAF V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation by AlphaScreen assay, IC50 = 0.044 μM. 29461827
A375 Function assay Inhibition of b-Raf in human A375 cells assessed phosphorylation of ERK, IC50 = 0.046 μM. 22808911
A375 Antiproliferative assay Antiproliferative activity against human A375 cells expressing B-Raf V600E mutant and wild type Ras, IC50 = 0.5 μM. 22808911
A375 Cytotoxicity assay 72 hrs Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 72 hrs by CellTiter-Glo assay, IC50 = 0.5 μM. 29461827
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells expressing wild type b-Raf and KRAS mutant, IC50 = 27 μM. 22808911
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
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Haga clic para ver más datos experimentales de líneas celulares

Información química, almacenamiento y estabilidad

Peso molecular 413.83 Fórmula

C17H14ClF2N3O3S

 Almacenamiento (Desde la fecha de recepción)
Nº CAS 918505-84-7 Descargar SDF Almacenamiento de soluciones madre

Sinónimos N/A Smiles CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)Cl)F

Solubilidad

In vitro
Lote:

DMSO : 83 mg/mL (200.56 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:

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)

mg/kg g μL

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

Targets/IC50/Ki
C-Raf-1 (Y340D/Y341D)
(Cell-free assay)
6.7 nM
B-Raf (V600E)
(Cell-free assay)
13 nM
BRK
(Cell-free assay)
130 nM
B-Raf
(Cell-free assay)
160 nM
In vitro
PLX-4720 muestra una selectividad >10 veces mayor contra B-Raf de tipo salvaje, y una selectividad >100 veces mayor sobre otras quinasas como Frk, Src, Fak, FGFR y Aurora A con una IC50 de 1,3-3,4 μM. Este compuesto inhibe significativamente la fosforilación de ERK en líneas celulares que expresan B-RafV600E con una IC50 de 14-46 nM, pero no en las células con B-Raf de tipo salvaje. Inhibe significativamente el crecimiento de líneas celulares tumorales que expresan el oncogén B-RafV600E, como COLO205, A375, WM2664 y COLO829 con una GI50 de 0,31 μM, 0,50 μM, 1,5 μM y 1,7 μM, respectivamente. Además, este tratamiento químico a 1 μM induce la detención del ciclo celular y la apoptosis exclusivamente en las células 1205Lu B-RafV600E-positivas, pero no en las células C8161 con B-Raf de tipo salvaje. Este tratamiento con el compuesto (10 μM) induce significativamente una expresión de BIM >14 veces mayor en las células PTEN+, en comparación con las líneas celulares PTEN- (4 veces), lo que explica la resistencia de las células PTEN- a esta apoptosis inducida por químicos.
Ensayo de quinasa
Actividades de la quinasa Raf in vitro
Las actividades de la quinasa Raf de tipo salvaje y de los mutantes in vitro se determinan midiendo la fosforilación de la proteína MEK biotinilada utilizando la tecnología AlphaScreen de Perkin-Elmer. Para cada enzima (0,1 ng), se realizan reacciones de 20 μL en 20 mM Hepes (pH 7,0), 10 mM MgCl2, 1 mM DTT, 0,01 % Tween-20, 100 nM de proteína biotin-MEK, diversas concentraciones de ATP y concentraciones crecientes de PLX-4720 a temperatura ambiente. Las reacciones se detienen a los 2, 5, 8, 10, 20 y 30 minutos con 5 μL de una solución que contiene 20 mM Hepes (pH 7,0), 200 mM NaCl, 80 mM EDTA y 0,3 % BSA. La solución de detención también incluye el anticuerpo phospho-MEK, microesferas donadoras recubiertas de estreptavidina y microesferas aceptoras de proteína A del kit de detección de proteína A AlphaScreen. El anticuerpo y las microesferas se preincuban en la solución de detención en la oscuridad a temperatura ambiente durante 30 minutos. La dilución final del anticuerpo es 1/2.000, y la concentración final de cada microesfera es 10 μg/mL. Las placas de ensayo se incuban a temperatura ambiente durante una hora y luego se leen en un lector AlphaQuest de PerkinElmer.
In vivo
La administración oral de PLX-4720 a 20 mg/kg/día induce retrasos y regresiones significativos del crecimiento tumoral en xenoinjertos tumorales COLO205 dependientes de B-RafV600E, sin efectos adversos obvios en ratones, incluso a una dosis de 1 g/kg. Este compuesto a 100 mg/kg dos veces al día elimina casi por completo los xenoinjertos 1205Lu que expresan B-RafV600E, mientras que no tiene actividad contra los xenoinjertos C8161 que expresan B-Raf de tipo salvaje. Los efectos antitumorales de este compuesto se correlacionan con el bloqueo de la vía MAPK en aquellas células que albergan la mutación V600E. Este tratamiento químico a 30 mg/kg/día inhibe significativamente el crecimiento tumoral de los xenoinjertos 8505c en >90 %, y disminuye drásticamente las metástasis pulmonares distantes.
Referencias

Aplicaciones

Métodos Biomarcadores Imágenes PMID
Western blot p-MEK / MEK / p-ERK / ERK / p-FAK(S910) p-EGFR 1173 / EGFR / p-Akt / Akt p27 / Cyclin D1 / pRb pAkt(Ser473) / pAkt(Thr308)
S1152-WB1
23076151
Immunofluorescence LAMP1 ZKSCAN3 / TFEB
S1152-IF1
30979895
Growth inhibition assay Cell viability
S1152-viability
27848137
ELISA mIFN-γ
S1152-ELISA1
23204132

Soporte técnico

Instrucciones de manipulación

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Preguntas frecuentes

Pregunta 1:
What would you recommend to make working solution for intraperitoneal injection into mice?

Respuesta:
Due to its very limited solubility in aqueous solution, this compound can be administered as a not fully dissolved suspension via oral gavage. For this reason, we recommend oral gavage for its administration.