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

Spring naar

Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.97%

99.97

Producten die vaak samen worden gebruikt met 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.

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

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	392.49	Formule	C₂₄H₂₈N₂O₃	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	873054-44-5	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	VX-770			Smiles	CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 79 mg/mL (201.27 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	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.
Kinase Assay	Ussing-kameropnames
Kinase Assay	Het effect van Ivacaftor (VX-770) op CFTR-gemedieerde Cl^- secretie wordt gekarakteriseerd door de CFTR-gemedieerde I_T te meten in kamers met behulp van recombinante Fisher-ratten schildklier (FRT) cellen die G551D of F508del CFTR tot expressie brengen. Cellen worden gekweekt op Costar Snapwell celkweekinzetstukken die op 37 °C worden gehouden vóór de opname. De celkweekinzetstukken worden gemonteerd in een Ussing-kamer om I_T op te nemen in de voltage-clamp modus (V_hold = 0 mV). Voor FRT-cellen wordt een basolateraal tot apicaal Cl^- gradiënt gecreëerd aan de basolaterale membraan. De basolaterale badoplossing bevat 135 mM NaCl, 1,2 mM CaCl₂, 1,2 mM MgCl₂, 2,4 mM K₂HPO₄, 0,6 mM KHPO₄, 10 mM N-2-hydroxyethylpiperazine-N
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/19846789/ [2] https://pubmed.ncbi.nlm.nih.gov/25441013/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	PPARγ / pERK NLRP3 Rδf508		30498130
Immunofluorescence	F-actin		30498130

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
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) CFTR-potentiator

Molecuulgewicht: 392.49

Kwaliteitscontrole (Quality Control)

Producten die vaak samen worden gebruikt met Ivacaftor (VX-770)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Ivacaftor (VX-770) CFTR-potentiator

Molecuulgewicht: 392.49

Kwaliteitscontrole (Quality Control)

Producten die vaak samen worden gebruikt met Ivacaftor (VX-770)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)