GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Ivacaftor (VX-770) Ivacaftor (VX-770) is a selective potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM in fisher rat thyroid cells, respectively.
In vitro

Ivacaftor (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, Ivacaftor (10 μM) increases the open probability (P_o) of G551D-, F508del-, and wild-type CFTR by ~6-fold, ~5-fold and ~2-fold, respectively, indicating that Ivacaftor 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 (10 μM) 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, Ivacaftor 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, Ivacaftor inhibits excessive ENaC-mediated Na⁺ and fluid absorption with an IC50 of 43 nM, and decreases the amiloride response, resulting in an increase in the surface fluid and cilia beat frequency (CBF) in G551D/F508del HBE.

In vivo

Cell Data

cell lines：

Concentrations：

Incubation Time：

Powder Purity:≥99%

Specifications

Synonyms

N-(2, 4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1, 4-dihydroquinoline-3-carboxamide

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Ivacaftor (VX-770) is a selective potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM in fisher rat thyroid cells, respectively.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

ACTIVATOR

Mechanism of action

Activator of CFTR

Product Properties

• ALogP: 5.6

Names and Identifiers

• Isomeric SMILES: CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C
• Molecular Weight: 392.49
• Reaxy-Rn: 11821038
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=11821038&ln=

Associated Targets(Human)

CFTR Tclin Cystic fibrosis transmembrane conductance regulator (0 Activities)

Discover Target: CFTR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)