IVACAFTOR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H28N2O3
Molecular Weight	392.4907
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C1=CC(=C(O)C=C1NC(=O)C2=CNC3=C(C=CC=C3)C2=O)C(C)(C)C

InChI

InChIKey=PURKAOJPTOLRMP-UHFFFAOYSA-N

InChI=1S/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)

HIDE SMILES / InChI

Molecular Formula	C24H28N2O3
Molecular Weight	392.4907
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203188s017lbl.pdf

Ivacaftor (trade names KALYDECO® (ivacaftor) and ORKAMBI® (lumacaftor/ivacaftor)) is a cystic fibrosis transmembrane conductance regulator potentiator indicated for the treatment of cystic fibrosis in patients age 6 years and older who have one of the following mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R. One such defect G551D is characterized by a dysfunctional CFTR protein on the cell surface. Although the defective protein is trafficked to the correct area, the epithelial cell surface, while there it cannot transport chloride through the channel. Ivacaftor, a CFTR potentiator, improves the transport of chloride through the ion channel by binding to the channels directly to induce a non-conventional mode of gating which in turn increases the probability that the channel is open. Ivacaftor regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cystic fibrosis transmembrane conductance regulator 7 Target ID: CHEMBL4051 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203188s017lbl.pdf	Activator 1447		100.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cystic fibrosis 120 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203188s017lbl.pdf	Primary		Approved 8583	KALYDECO Approved Use KALYDECO is indicated for the treatment of CF in patients age 6 years and older who have an R117H mutation in the CFTR gene Launch Date 2012

C_max

Value	Dose	Co-administered	Analyte	Population
2212 ng/mL EXPERIMENT http://www.concertpharma.com/wp-content/uploads/2015/10/CTP656-Ph1SAD-NACFC-08OCT2015.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		IVACAFTOR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
44916 ng × h/mL EXPERIMENT http://www.concertpharma.com/wp-content/uploads/2015/10/CTP656-Ph1SAD-NACFC-08OCT2015.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		IVACAFTOR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
15 h EXPERIMENT http://www.concertpharma.com/wp-content/uploads/2015/10/CTP656-Ph1SAD-NACFC-08OCT2015.pdf	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		IVACAFTOR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

Doses

Dose	Population	Adverse events
50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2 years Health Status: unhealthy Age Group: 2 years Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	Disc. AE: ALT increased... AEs leading to discontinuation/dose reduction: ALT increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	Disc. AE: Elevated liver enzymes, Croup... AEs leading to discontinuation/dose reduction: Elevated liver enzymes (2 patients) Croup (1 patient) Sepsis (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	Disc. AE: Elevated liver enzymes, Vomiting... AEs leading to discontinuation/dose reduction: Elevated liver enzymes (1 patient) Vomiting (2 patients) Gastroenteritis (1 patient) Retching (1 patient) Rash (1 patient) Cough increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
450 mg 2 times / day multiple, oral Overdose Dose: 450 mg, 2 times / day Route: oral Route: multiple Dose: 450 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf	Other AEs: Dizziness, Diarrhea... Other AEs: Dizziness Diarrhea Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf

AEs

AE	Significance	Dose	Population
ALT increased	1 patient Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2 years Health Status: unhealthy Age Group: 2 years Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Croup	1 patient Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Sepsis	1 patient Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Elevated liver enzymes	2 patients Disc. AE	50 mg 2 times / day steady, oral Recommended Dose: 50 mg, 2 times / day Route: oral Route: steady Dose: 50 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Cough increased	1 patient Disc. AE	75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Elevated liver enzymes	1 patient Disc. AE	75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Gastroenteritis	1 patient Disc. AE	75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Rash	1 patient Disc. AE	75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Retching	1 patient Disc. AE	75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Vomiting	2 patients Disc. AE	75 mg 2 times / day steady, oral Recommended Dose: 75 mg, 2 times / day Route: oral Route: steady Dose: 75 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf	unhealthy, 2-6 years Health Status: unhealthy Age Group: 2-6 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207925Orig1s000MedR.pdf
Diarrhea		450 mg 2 times / day multiple, oral Overdose Dose: 450 mg, 2 times / day Route: oral Route: multiple Dose: 450 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf
Dizziness		450 mg 2 times / day multiple, oral Overdose Dose: 450 mg, 2 times / day Route: oral Route: multiple Dose: 450 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207925s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 2438 inducer 440	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227 P-gp 1741 CYP2C8 1057 Cav1.2 58 Kv1.5 27 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C19 2057 CYP2E1 1060	CYP3A 220 CYP2C 16 P-gp 2052	CYP1A2 832 CYP2A6 86 CYP2B6 669 CYP2C8 198 CYP2C19 329 CYP3A4/5 133

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 52.0	no
CYP2A6 911	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 52.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 52.0	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 52.0	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 52.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 52.0	no
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 6.0	weak [IC50 11 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 6.0	weak [IC50 3.8 uM]
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 3.0	weak [IC50 41 uM]	weak (co-administration study) Comment: ivacaftor increased midazolam exposure 1.5x, cmax 1.38x, auc 1.54x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 3.0
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 3.0	yes [IC50 0.17 uM]
Kv1.5 42	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 34.0	yes [IC50 3.4 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 3.0	major	yes (co-administration study) Comment: ketoconazole increased ivacaftor exposure by 8.5x; fluconazole increased ivacaftor exposure by 3x; rifampin decreased ivacaftor exposure by 9x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 3.0
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 35.0	no
CYP2C 16	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 6.0	no	no (co-administration study) Comment: rosiglitazone had no effect on cmax and auc of ivacaftor Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 6.0
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 6.0	no	no (co-administration study) Comment: desipramine had no effect on cmax and auc of ivacaftor Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203188lbl.pdf Page: 6.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 63	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 34.0
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203188Orig1s000PharmR.pdf Page: 59.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:66901	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:66901
ChemicalBook	CB32506174	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32506174
eMolecules	32278030	https://www.emolecules.com/cgi-bin/more?vid=32278030
MolPort	MolPort-009-194-229	https://www.molport.com/shop/molecule-link/MolPort-009-194-229
Selleck Chemicals	VX-770	http://www.selleckchem.com/products/VX-770.html
ZINC	ZINC000052509463	http://zinc15.docking.org/substances/ZINC000052509463

PubMed

Title	Date	PubMed
Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner.	2012-10-26	22942289
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.	2011-11-03	22047557
Probing conformational rescue induced by a chemical corrector of F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutant.	2011-07-15	21602569
Cystic fibrosis transmembrane regulator potentiators as promising cystic fibrosis therapies.	2011-03	21303308
Targeting the basic defect in cystic fibrosis.	2010-11-18	21083391
Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation.	2010-11-18	21083385
Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770.	2009-11-03	19846789

Patents

Sample Use Guides

In Vivo Use Guide

Adults and pediatric patients age 6 years and older: one 150 mg tablet taken orally every 12 hours with fat-containing food. Reduce dose in patients with moderate and severe hepatic impairment. Reduce dose when co-administered with drugs that are moderate or strong CYP3A inhibitors.

Route of Administration: Oral

In Vitro Use Guide

10 uM ivacaftor increased the channel open probability of all CFTR gating mutations tested, reaching levels equivalent to 30% to 118% of normal CFTR.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:26:41 GMT 2025` Edited by `admin` on `Mon Mar 31 18:26:41 GMT 2025`
Record UNII	1Y740ILL1Z
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ORKAMBI COMPONENT IVACAFTOR

Preferred Name

English

IVACAFTOR

Official Name

English

N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-4-oxo-1,4-dihydroquinoline-3-carboxamide

Systematic Name

English

ivacaftor [INN]

Common Name

English

TRIKAFTA COMPONENT IVACAFTOR

Brand Name

English

IVACAFTOR [VANDF]

Common Name

English

IVACAFTOR [ORANGE BOOK]

Common Name

English

IVACAFTOR [MI]

Common Name

English

3-QUINOLINECARBOXAMIDE, N-(2,4-BIS(1,1-DIMETHYLETHYL)-5-HYDROXYPHENYL)-1,4-DIHYDRO-4-OXO-

Systematic Name

English

IVACAFTOR [USAN]

Common Name

English

VX-770

Code

English

KALYDECO

Brand Name

English

SYMKEVI COMPONENT IVACAFTOR

Brand Name

English

Ivacaftor [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

647618