Ivacaftor

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Cat Number

API873054445

CAS Number

873054-44-5

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Product Detail Description Scientific Support Customer Q&A

CAS Number

873054-44-5

EINECS

800-027-5

Storage

Store at room temperature

Synonyms

VX-770; Kalydeco; N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide; ivacaftorum; 1Y740ILL1Z

Molecular Formula

C24H28N2O3

Molecular Weight

392.5

Smiles

CC(C)(C)C1=CC(=C(C=C1NC(=O)C2=CNC3=CC=CC=C3C2=O)O)C(C)(C)C

Appearance

White to off-white solid

Melting Point

212-215°C

Boiling Point

550.4±50.0°C (Predicted)

Relative Density

1.187

General Description

Ivacaftor is a first-in-class CFTR potentiator, a small molecule that enhances the gating function of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel.

Mechanism of Action

Ivacaftor binds reversibly to both wild-type and mutant CFTR proteins, increasing the open probability of the channel via an ATP-independent mechanism. It acts by stabilizing the channel's open conformation, even in the absence of ATP, thereby enhancing cAMP/PKA-signaling mediated gating activity. This non-conventional mode of gating restores chloride transport across epithelial cell membranes.

Application

Ivacaftor is indicated for the treatment of cystic fibrosis in patients with specific G551D and other gating mutations, where it improves respiratory function and reduces sweat chloride levels. It is also used in combination with lumacaftor (a CFTR corrector) for patients homozygous for the F508del mutation to improve the processing and activity of defective CFTR.

In a phase 3, double‑blind, placebo‑controlled trial involving 403 patients with cystic fibrosis with Phe508del‑minimal function genotypes (for whom previous CFTR modulators were ineffective), elexacaftor‑tezacaftor‑ivacaftor for 24 weeks significantly improved percentage of predicted FEV₁ (13.8 points at week 4, 14.3 points through 24 weeks), reduced pulmonary exacerbations by 63%, improved quality‑of‑life respiratory scores, and lowered sweat chloride concentration (all P<0.001). Adverse events were generally mild or moderate, with only 1% discontinuing. The triple combination is highly efficacious in this previously difficult‑to‑treat genotype.

Fig. 1 Absolute Change from Baseline in Percentage of Predicted FEV1, and Rate of Pulmonary Exacerbations. (Middleton PG, et al., 2019)

References

Middleton PG, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381(19):1809-1819.

Does Ivacaftor require protection from light during storage?

Yes, it is photosensitive. UV exposure can cause photodegradation of the quinoline ring. Store in light-resistant containers, preferably original opaque packaging.

What is the recommended storage temperature for Ivacaftor?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can soften the powder and accelerate oxidative degradation.

Is Ivacaftor stable under high-humidity conditions?

It is not hygroscopic and shows good stability. However, store in tightly sealed containers to prevent any potential surface absorption of moisture.

How is the impurity ivacaftor N-oxide (an oxidative degradation product) monitored?

This degradation product is quantified using a stability-indicating HPLC method, ensuring it remains within ICH qualification thresholds.