Name: Ivacaftor (VX-770)
Brand: Selleck Chemicals
SKU: S1144
Rating: 5 (280 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.97%

99.97

Productos que se suelen utilizar junto con Ivacaftor (VX-770)

Tezacaftor (VX-661)

Tezacaftor specifically targets F508del CFTR whereas, this compound targets both G551D-CFTR and F508del-CFTR.

VX-445 (Elexacaftor)

Elexacaftor exhibits multiplicative synergy with it in potentiating Class III and IV CFTR mutations.

CFTRinh-172

This compound is a CFTR potentiator, whereas CFTRinh-172 is an CFTR inhibitor.

Icenticaftor (QBW251)

It and Icenticaftor are small-molecule channel potentiators of CFTR that are under clinical trials for their roles in chronic obstructive pulmonary disease.

Dianas relacionadas	CRM1 CD markers AChR Calcium Channel Sodium Channel Potassium Channel GABA Receptor TRP Channel ATPase GluR
Otros CFTR Inhibidores	Vanzacaftor (VX-121) GLPG1837 Galicaftor (ABBV-2222) GlyH-101 FDL169 IOWH032 PPQ-102 Nesolicaftor (PTI-428) KM11060 Steviol (Hydroxydehydrostevic acid)

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

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	PMID
HBE	Function Assay	10 μM	10 min	augments CFTR-dependent ion transport	24106801
CFBE41o-	Function Assay	10 µM		induces robust increases in anion transport	22768130
HBE	Function Assay	10 µM		augments CFTR-dependent anion transport activity	22768130
HBE	Function Assay	10 µM	24 h	induces a modest but significant increase in ASL depth	22768130
HBE	Function Assay	10 µM		potentiates CFTR-dependent Isc, regardless of prior administration of CSE	22768130
HBE	Function Assay	10 µM		partially restores depletion of ASL depth in CSE treated monolayers	22768130
mouse NIH-3T3 cells	Function assay		30 mins	Potentiation of human CFTR F508del mutant expressed in mouse NIH-3T3 cells after 30 mins by fluorescent voltage sensing optical assay, EC50 = 0.003 μM.	25441013
human bronchial epithelial cells	Function assay			Potentiation of human CFTR F508del/G551D mutant in human bronchial epithelial cells by Ussing chambers recording technique, EC50 = 0.022 μM.	25441013
human CFBE41o cells	Function assay		10 mins	Potentiation of CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells incubated for 10 mins in presence of forskolin measured for 7 secs by YFP halide assay, EC50 = 0.126 μM.	29148763
human bronchial epithelial cells	Function assay			Potentiation of human CFTR F508del mutant in human bronchial epithelial cells by Ussing chambers recording technique, EC50 = 0.236 μM.	25441013
HEK293 cells	Function assay		10 mins	Potentiation of CFTR G551D mutant (unknown origin) expressed in HEK293 cells incubated for 10 mins in presence of forskolin measured for 2 mins by YFP halide assay, EC50 = 1.3 μM.	29148763
NRK-49F cells	Function assay			Inhibition of TGF-beta1-induced total collagen accumulation in rat NRK-49F cells, IC50 = 4 μM.	25467157
DAOY cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1 cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
MG 63 (6-TG R) cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
RD cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
SK-N-MC cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
Saos-2 cells	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	392.49	Fórmula	C₂₄H₂₈N₂O₃	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	873054-44-5	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	VX-770			Smiles	CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 79 mg/mL (201.27 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.
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.	5.500mg/ml (14.01mM)	Taking the 1 mL working solution as an example, add 50 μL of 110 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 make it clear; 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.

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)

Características	The first potent and orally available CFTR potentiator to enter human clinical trials.
Targets/IC₅₀/Ki	F508del-CFTR (Fisher rat thyroid cells) 25 nM(EC50) G551D-CFTR (Fisher rat thyroid cells) 100 nM(EC50)
In vitro	Ivacaftor (VX-770) (10 μM) significantly increases the forskolin-stimulated Cl^- secretion (I_T) by ~4-fold with an EC50 of 100 nM in the recombinant Fisher rat thyroid (FRT) cells expressing G551D gating mutation of CFTR, and by ~6-fold with an EC50 of 25 nM in the recombinant cells expressing temperature-corrected F508del processing mutation of CFTR. Consistent with the increases in the forskolin-stimulated I_T, this compound increases the open probability (P_o) of G551D-, F508del-, and wild-type CFTR by ~6-fold, ~5-fold and ~2-fold, respectively, indicating that it acts directly on CFTR to increase its gating activity. In primary cultured human CF bronchial epithelia (HBE) carrying the G551D and F508del CFTR mutations, Ivacaftor potently increases the forskolin-stimulated I_T by ~10-fold from 5% to a maximum level of 48% of that measured in non-CF HBE, with an EC50 of 236 nM displaying ~70-fold more potency compared with the commonly used CFTR potentiator genistein, which has an EC50 of 16 μM. In HBE with F508del homozygous CFTR, it causes a significant increase in the forskolin-stimulated I_T with an EC50 of 22 nM, to a less extent from 4% to 16% of non-CF HBE compared with the effect in G551D/F508del HBE. Due to CFTR potentiation, this compound inhibits excessive ENaC-mediated Na⁺ and fluid absorption with an IC50 of 43 nM, and decreases the response, resulting in an increase in the surface fluid and cilia beat frequency (CBF) in G551D/F508del HBE.
Ensayo de quinasa	Registros de cámara de Ussing
Ensayo de quinasa	El efecto de Ivacaftor (VX-770) sobre la secreción de Cl^- mediada por CFTR se caracteriza midiendo la I_T mediada por CFTR en cámaras utilizando células tiroideas de rata Fisher (FRT) recombinantes que expresan G551D o F508del CFTR. Las células se cultivan en insertos de cultivo celular Costar Snapwell mantenidos a 37 °C antes del registro. Los insertos de cultivo celular se montan en una cámara de Ussing para registrar la I_T en el modo de fijación de voltaje (V_hold = 0 mV). Para las células FRT, la membrana basolateral es un gradiente de Cl^- basolateral a apical. La solución de baño basolateral contiene 135 mM de NaCl, 1,2 mM de CaCl₂, 1,2 mM de MgCl₂, 2,4 mM de K₂HPO₄, 0,6 mM de KHPO₄, 10 mM de N-2-hidroxietilpiperazina-N
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/19846789/ [2] https://pubmed.ncbi.nlm.nih.gov/25441013/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	PPARγ / pERK NLRP3 Rδf508		30498130
Immunofluorescence	F-actin		30498130

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
NCT06331000	Not yet recruiting	Cystic Fibrosis	University Hospital Strasbourg France	March 2024	--
NCT05519020	Recruiting	Cystic Fibrosis	Sheffield Teaching Hospitals NHS Foundation Trust	July 27 2022	--
NCT04254705	Withdrawn	Cystic Fibrosis	Universitaire Ziekenhuizen KU Leuven\|Vertex Pharmaceuticals Incorporated\|KU Leuven\|University of Lisbon	March 1 2020	Not Applicable
NCT03085485	Completed	Chronic Obstructive Pulmonary Disease\|Chronic Bronchitis	University of Alabama at Birmingham\|National Heart Lung and Blood Institute (NHLBI)\|Vertex Pharmaceuticals Incorporated	March 16 2017	Phase 2

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):

Ivacaftor (VX-770) Potenciador de CFTR

Peso molecular: 392.49

Control de calidad (Quality Control)

Productos que se suelen utilizar junto con Ivacaftor (VX-770)

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)

Ivacaftor (VX-770) Potenciador de CFTR

Peso molecular: 392.49

Control de calidad (Quality Control)

Productos que se suelen utilizar junto con Ivacaftor (VX-770)

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)

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