solo para uso en investigación

Tariquidar (XR9576) P-gp inhibidor

Cat. No.S8028

Tariquidar es un inhibidor no competitivo potente y selectivo de la P-glicoproteína con un Kd de 5,1 nM en la línea celular CHrB30, que revierte la resistencia a fármacos en líneas celulares MDR. Fase 3.
Tariquidar (XR9576) P-gp inhibidor Chemical Structure

Estructura química

Peso molecular: 646.73

Saltar a

Control de calidad

Lote: Pureza: 99.81%
99.81

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares Tipo de ensayo Concentración Tiempo de incubación Formulación Descripción de la actividad PMID
K562/DOX Function assay 1 uM 10 mins Inhibition of P-gp in human K562/DOX cells assessed as increase in rhodamine-123 efflux in human K562 cells at 1 uM incubated for 10 mins hrs by flow cytometry relative to untreated control 28113128
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
KB-V1 Function assay 200 nM Inhibition of P-gp in human KB-V1 cells assessed as increase in rhodamine 123 accumulation at 200 nM 21657271
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
HepG2 Cytotoxicity assay 48 hrs Cytotoxicity against adriamycin-resistant human HepG2 cells assessed as inhibition of cell proliferation after 48 hrs by MTT assay, IC50=37.2μM 27328029
K562 Cytotoxicity assay 48 hrs Cytotoxicity against human K562 cells after 48 hrs by MTT assay, IC50=31.56μM 28645831
K562 Cytotoxicity assay 48 hrs Cytotoxicity against human K562 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=31.56μM 29631786
A2780adr Function assay 10 uM 30 mins Inhibition of ABCB1 in human A2780adr cells assessed as increase in accumulation of calcein AM at 10 uM preincubated for 30 mins followed by calcein AM addition measured every 60 secs for 60 mins by fluorescence assay relative to control 29547272
K562/A02 Cytotoxicity assay 48 hrs Cytotoxicity against human K562/A02 cells overexpressing P-gp assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=27.19μM 29631786
CCD-18Co Cytotoxicity assay 48 hrs Cytotoxicity against human CCD-18Co cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM 26197160
SW620/AD300 Cytotoxicity assay 48 hrs Cytotoxicity against human SW620/AD300 cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM 26197160
HLF Cytotoxicity assay 48 hrs Cytotoxicity against HLF cells assessed as inhibition of cell proliferation after 48 hrs by MTT assay, IC50=16.69μM 27328029
CEM/VLB500 Growth inhibition assay 3 days Growth inhibition of human CEM/VLB500 cells after 3 days by resazurin assay, GI50=13.5μM 17399990
MCF7/ADR Cytotoxicity assay 48 hrs Intrinsic cytotoxicity against human MCF7/ADR cells assessed as inhibition of cell proliferation after 48 hrs by MTT assay, IC50=13.1μM 27328029
HCT116 Cytotoxicity assay 48 hrs Cytotoxicity against human HCT116 cells assessed as cell viability after 48 hrs by MTT assay, IC50=12.5μM 26197160
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured after 12 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=8.28μM 28645831
KBV Function assay 5 uM 72 hrs Reversal of P-gp-mediated drug resistance in human KBV cells assessed as potentiation of cytotoxicity by measuring IC50 at 5 uM after 72 hrs by MTT assay (Rvb = 398.34 +/- 0.58 uM), IC50=5.24μM 30384042
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured after 6 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=4.97μM 28645831
KBV Function assay 10 uM 72 hrs Reversal of P-gp-mediated drug resistance in human KBV cells assessed as potentiation of cytotoxicity by measuring IC50 at 10 uM after 72 hrs by MTT assay (Rvb = 398.34 +/- 0.58 uM), IC50=4.46μM 30384042
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured immediately by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=3.02μM 28645831
K562/A02 Function assay 5 uM 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 at 5 uM measured after 48 hrs by MTT assay (Rvb = 43.75 to 96.91 uM), IC50=1.97μM 28645831
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 measured after 48 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=1.6μM 28645831
MCF-7 MX Function assay Inhibition of BCRP expressed in MCF-7 MX cells using Hoechst 33342 staining, IC50=1.5μM 21354800
MCF7 Function assay Inhibition of ABCG2 in human mitoxantrone-resistant MCF7 cells by Hoechst 33342 assay, IC50=1.44544μM 18678495
HFE Cytotoxicity assay 72 hrs Cytotoxicity against human HFE cells assessed as cell viability after 72 hrs by MTT assay, IC50=1.28μM 26197160
MDCK Function assay Inhibition of BCRP expressed in MDCK cells using Hoechst 33342 staining, IC50=0.94μM 21354800
MCF7/Topo Function assay Inhibition of ABCG2 overexpressed in human MCF7/Topo cells by flow cytometric-based mitoxantrone efflux assay, IC50=0.916μM 19170519
MCF7/Topo Function assay 2 hrs Inhibition of ABCG2 in human MCF7/Topo cells after 2 hrs by Hoechst 33342 staining based fluorescence assay, IC50=0.526μM 30128080
MCF7/Topo Function assay 2 hrs Inhibition of ABCG2 in human MCF7/Topo cells after 2 hrs by Hoechst 33342 microplate assay, IC50=0.526μM 24900683
MCF7/Topo Function assay Inhibition of ABCG2 expressed in human MCF7/Topo cells by Hoechst microplate assay, IC50=0.526μM 21570282
MCF7/Topo Function assay Inhibition of ABCG2 in human MCF7/Topo cells by Hoechst 33342 assay, IC50=0.52μM 26774038
KBV1 Function assay 10 mins Inhibition of ABCB1 in human KBV1 cells after 10 mins by Calcein-AM microplate assay, IC50=0.223μM 24900683
Kb-V1 Function assay 10 mins Inhibition of ABCB1 expressed in Kb-V1 cells after 10 mins by calcein-AM assay, IC50=0.223μM 21570282
KBv1 Function assay Inhibition of ABCB1 overexpressed in human KBv1 cells by flow cytometric-based calcein-AM efflux assay, IC50=0.223μM 19170519
KBV1 Function assay Inhibition of ABCB1 in human KBV1 cells assessed as inhibition of calcein-AM efflux, IC50=0.22μM 26774038
A2780 Function assay 30 mins Inhibition of human Pgp in A2780 cells after 30 mins by Hoechst 33342 assay, IC50=0.12589μM 18083034
KB-3-1 Function assay 1000 nM 72 hrs Potentiation of doxorubicin-induced cytotoxicity against human KB-3-1 cells assessed as doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 0.15 +/- 0.04 uM), IC50=0.11μM 27504669
OVCAR8 Function assay 1000 nM 72 hrs Potentiation of doxorubicin-induced cytotoxicity against human OVCAR8 cells assessed as doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 0.12 +/- 0.03 uM), IC50=0.08μM 27504669
A2780/ADR Function assay Inhibition of P-glycoprotein-mediated multidrug resistance in adriamycin-resistant human A2780/ADR cells by calcein AM assay, IC50=0.078μM 19250834
A2780adr Function assay Inhibition of P-gp expressed in A2780adr cells by calcein AM accumulation assay, IC50=0.08μM 21354800
A2780 Function assay Inhibition of P-gp in human adriamycin-resistant A2780 cells by Hoechst 33342 assay, IC50=0.07244μM 18678495
KBV1 Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in KBV1 cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 5.07 +/- 0.19 uM), IC50=0.07μM 27504669
CEM/VLB500 Function assay 3 days Reversal of P-gp-mediated multidrug resistance to in human CEM/VLB500 cells after 3 days by resazurin assay, EC50=0.068μM 17399990
EMT6/AR1.0 Function assay 1 hr Inhibition of mouse Pgp in EMT6/AR1.0 cells after 1 hr by daunorubicin accumulation assay, IC50=0.06457μM 18083034
EMT6/AR1.0 Function assay 1 hr Inhibition of mouse Pgp in EMT6/AR1.0 cells after 1 hr by daunorubicin accumulation assay, IC50=0.064μM 18083034
MDCK Function assay 30 mins Inhibition of P-glycoprotein (unknown origin) expressed in MDCK cells assessed as reduction of calcein-AM transport after 30 mins by fluorescence assay, EC50=0.044μM 24607999
MDCK Function assay 30 mins Activity at MDR1 (unknown origin) expressed in MDCK cells using calcein AM as substrate incubated for 30 mins prior to substrate addition measured after 30 mins by fluorometric analysis, EC50=0.044μM 23374872
NCI-ADR-RES Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in NCI-ADR-RES cells assessed as potentiation of cytotoxicity by measuring IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 3714.80 +/- 383.58 nM), IC50=0.01851μM 27504669
KBV1 Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in KBV1 cells assessed as potentiation of cytotoxicity by measuring IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 277.68 +/- 56.61 nM), IC50=0.00066μM 27504669
HEK293 Function assay 1000 nM 72 hrs Potentiation of doxorubicin-induced cytotoxicity against HEK293 cells assessed as doxorubicin IC50 at 1000 nM after 72 hrs by CCK8 assay (Rvb = 5.28 +/- 0.74 nM), IC50=0.00495μM 27504669
K562/A02 Cytotoxicity assay 48 hrs Cytotoxicity against human K562/A02 cells after 48 hrs by MTT assay, IC50=27.19μM 28645831
SW620 Cytotoxicity assay 48 hrs Cytotoxicity against human SW620 cells assessed as cell viability after 48 hrs by MTT assay, IC50=25μM 26197160
K562/A02 Function assay 48 hrs Inhibition of ABCB1 in human K562/A02 cells assessed as potentiation of adriamycin-induced cytotoxicity by measuring ADR IC50 treated for 48 hrs followed by compound washout measured after 24 hrs by MTT assay (Rvb = 51.34 +/- 5.1 uM), IC50=14.39μM 28645831
MDCK Function assay Inhibition of BCRP expressed in MDCK cells by pheophorbide A assay, IC50=0.85μM 19932960
MCF7 MX Function assay Inhibition of BCRP expressed in MCF7 MX cells by Hoechst 33342 staining, IC50=0.68μM 19932960
NCI-ADR-RES Function assay 1000 nM 72 hrs Inhibition of human ABCB1 expressed in NCI-ADR-RES cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 5.54 +/- 0.60 uM), IC50=0.24μM 27504669
MDCK Function assay Inhibition of MDR1 expressed in MDCK cells using rhodamine 123 staining by flow cytometry, IC50=0.21μM 21354800
CCRF-CEM/VCR1000 Function assay 240 secs Inhibition of P-glycoprotein-mediated daunorubicin efflux from human CCRF-CEM/VCR1000 cells after 240 secs by FACS flow cytometric analysis, IC50=0.03311μM 22452412
HEK293 Function assay 1000 nM 72 hrs Inhibition of human ABCB1 transfected in HEK293 cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 1000 nM after 72 hrs by CCK8 assay (Rvb = 504.65 +/- 44.94 nM), IC50=0.02477μM 27504669
KB-3-1 Function assay 1000 nM 72 hrs Potentiation of cytotoxicity against human KB-3-1 cells assessed as IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 0.78 +/- 0.27 nM), IC50=0.00041μM 27504669
OVCAR8 Function assay 1000 nM 72 hrs Potentiation of cytotoxicity against human OVCAR8 cells assessed as IC50 at 1000 nM after 72 hrs by MTT assay (Rvb = 8.53 +/- 1.95 nM), IC50=0.00518μM 27504669
MDCK Function assay 30 mins Activity at BCRP (unknown origin) expressed in MDCK cells using rhodamine 123 as substrate incubated for 30 mins prior to substrate addition measured after 30 mins by fluorometric analysis, EC50=0.01μM 23374872
HepG2 Function assay 10 uM 90 mins Inhibition of P-gp mediated efflux in adriamycin-resistant human HepG2 cells assessed as intracellular rhodamine-123 accumulation at 10 uM incubated in dark condition for 90 mins by flow cytometry relative to control 27328029
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Información química, almacenamiento y estabilidad

Peso molecular 646.73 Fórmula

C38H38N4O6

Almacenamiento (Desde la fecha de recepción)
Nº CAS 206873-63-4 Descargar SDF Almacenamiento de soluciones madre

Sinónimos XR9576 Smiles COC1=C(C=C2CN(CCC2=C1)CCC3=CC=C(C=C3)NC(=O)C4=CC(=C(C=C4NC(=O)C5=CC6=CC=CC=C6N=C5)OC)OC)OC

Solubilidad

In vitro
Lote:

DMSO : 8 mg/mL (12.36 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
P-gp
(CHrB30 cells)
5.1 nM(Kd)
In vitro

Tariquidar muestra una unión de alta afinidad a la P-gp con una Bmax de 275 pmol/mg. Este compuesto muestra una interacción no competitiva con los sustratos de P-gp. Aumenta la acumulación en estado estacionario de estos citotóxicos en células CHrB30 a niveles observados en células AuxB1 que no expresan P-gp con una EC50 de 487 nM. Este químico es capaz de inhibir la actividad ATPasa sensible al vanadato de la P-gp en un 60-70%, con potentes valores de IC50 de 43 nM. Puede inhibir otros mecanismos de resistencia a concentraciones más altas. 1 µM de este compuesto anula la resistencia mediada por ABCG2 (BCRP) a las camptotecinas in vitro. Potencia la citotoxicidad de varios fármacos, incluida la doxorrubicina; se logra una reversión completa de la resistencia en presencia de 25-80 nM de este químico. En MC26, una línea celular de carcinoma de colon murino con quimiorresistencia intrínseca, la IC50 de doxorrubicina es cinco veces menor en presencia de 0,1 µM de este compuesto (36 frente a 7 nM). En líneas celulares de carcinoma mamario murino, carcinoma de pulmón de células pequeñas humano y carcinoma ovárico humano con resistencia quimioterapéutica adquirida (EMT6/AR1.0, H69/LX4 y 2780 AD), la IC50 de doxorrubicina in vitro es 22-150 veces menor en presencia de 0,1 µM de este químico. La inhibición de P-gp persiste durante 23 h después de su eliminación del sistema de cultivo. Restauró la citotoxicidad de la doxorrubicina en el modelo de esferoide tumoral multicelular NCI/ADRRES (National Cancer Institute) derivado de la línea celular de cáncer de mama MCF7WT.

Ensayo de quinasa
Ensayo de acumulación de fármacos en estado estacionario
Las células se incuban en un volumen de reacción de 1 mL durante 60 min a 37 ℃ bajo 5% de CO2 para alcanzar el estado estacionario. El efecto de los moduladores XR9576 sobre la acumulación del ligando [3H] se investiga en el rango de concentración de 10-9 - 10-6 M. Este compuesto se añade a partir de una solución madre de DMSO, dando una concentración final de disolvente del 0,2 % (v/v). Después de la recolección celular, el fármaco acumulado se mide mediante recuento por centelleo líquido y se normaliza según el contenido de proteína celular. Las gráficas de la cantidad acumulada en función de la concentración del modulador se ajustan con la ecuación general dosis-respuesta: Y={(a-b)/(1+(X/c)d)}+b, donde: Y=respuesta; a=respuesta inicial; b=respuesta final; c=concentración EC50; d=valor de la pendiente; X=concentración del fármaco.
In vivo

Se ha descubierto que Tariquidar (2-8 mg/kg p.o.) potencia significativamente la actividad antitumoral de la doxorrubicina (5 mg/kg, i.v.) contra el carcinoma de colon murino MC26 in vivo. En xenoinjertos de carcinoma humano, la coadministración de este compuesto (6-12 mg/kg p.o.) restauró completamente la actividad antitumoral contra dos xenoinjertos tumorales humanos MDR altamente resistentes (2780AD, H69/LX4) en ratones nude.

Referencias
  • [4] https://pubmed.ncbi.nlm.nih.gov/14962729/

Aplicaciones

Métodos Biomarcadores Imágenes PMID
Immunofluorescence MRP7
S8028-IF1
23393594

Información del ensayo clínico

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

Número NCT Reclutamiento Condiciones Patrocinador/Colaboradores Fecha de inicio Fases
NCT01663545 Completed
Epilepsies Partial
National Institute of Neurological Disorders and Stroke (NINDS)|National Institutes of Health Clinical Center (CC)
July 31 2012 --
NCT01547754 Terminated
HIV-Associated Cognitive Motor Complex
National Institute of Mental Health (NIMH)|National Institutes of Health Clinical Center (CC)
January 9 2012 --
NCT01386476 Completed
Drug Resistance
National Institute of Mental Health (NIMH)|National Institutes of Health Clinical Center (CC)
June 15 2011 --
NCT00082368 Completed
Cancer
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
May 16 2004 Phase 2

Soporte técnico

Instrucciones de manipulación

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Preguntas frecuentes

Pregunta 1:
Can you please give me more specific and detailed information of how to dissolve and use it (S8028) for in vivo studies?

Respuesta:
It in 30% Propylene glycol, 5% Tween 80, 65% D5W at 30mg/ml will be a suspension or emulsion. If you are going to administrate this compound by oral gavage, it is fine. We also have test some vehicles for it for i.p injection, and it is soluble in 5% DMSO+45% PEG 300+ddH2O at 2mg/ml clearly. When preparing the solution, please dissolve it in DMSO clearly first, then add PEG. After they mixed well, then dilute with water.