Ivacaftor

Summary

Ivacaftor (CHEMBL2010601) is an approved small-molecule CFTR potentiator (ATC R07AX02) targeting CFTR; indicated across 7 conditions including respiratory system disorder and cystic fibrosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R07AX02
• Targets: 1 (CFTR)
• Indications: 7 conditions
• Clinical trials: 72
• Chemistry: 392.5 Da · C24H28N2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2010601
Name	Ivacaftor
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	16220172
ChEBI	CHEBI:66901
ATC	R07AX02
Molecular formula	C24H28N2O3
Molecular weight	392.5
InChIKey	PURKAOJPTOLRMP-UHFFFAOYSA-N

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

IUPAC name: N-(2,4-ditert-butyl-5-hydroxyphenyl)-4-oxo-1H-quinoline-3-carboxamide

ChEBI definition: An aromatic amide obtained by formal condensation of the carboxy group of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid with the amino group of 5-amino-2,4-di-tert-butylphenol. Used for the treatment of cystic fibrosis.

Pharmacological roles (ChEBI): CFTR potentiator, orphan drug.

Also known as: Ivacaftor, Ivacaftor component of orkambi, Ivacaftor component of symkevi, Ivacaftor component of trikafta, Kalydeco, VX-770, IVACAFTOR, SID124950685, IVACAFTOR (VX-770), IvacaftorÊ, Ivacaftor (VX-770), IvacaftorÂ

Parent form; salt/anhydrous children: CHEMBL4297603

Patent coverage: 899 distinct patent families (2,662 SureChEMBL compound mentions), from 4 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CFTR	CFTR	Potentiation	8.52	0.1%	P13569

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Thromboxane A2 receptor, Sodium-dependent noradrenaline transporter, Type-1 angiotensin II receptor, Prostaglandin G/H synthase 2, Sodium-dependent dopamine transporter, Beta-3 adrenergic receptor, Adenosine receptor A3, Melanocortin receptor 4, Cystic fibrosis transmembrane conductance regulator.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 29 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CFTR	8.52	EC50	3	nM	CHEMBL_ACT_15136254
CFTR	8.52	EC50	3	nM	CHEMBL_ACT_15140378
CFTR	7.93	EC50	11.7	nM	CHEMBL_ACT_22958252
CFTR	7.9	EC50	12.59	nM	CHEMBL_ACT_25523839
CFTR	7.89	EC50	13	nM	CHEMBL_ACT_25523838
CFTR	7.66	EC50	22	nM	CHEMBL_ACT_15065262
CFTR	7.6	EC50	25	nM	CHEMBL_ACT_25500437
CFTR	7.47	EC50	34	nM	CHEMBL_ACT_24375515
CFTR	7.33	EC50	46.6	nM	CHEMBL_ACT_29226362
CFTR	7.31	EC50	49	nM	CHEMBL_ACT_24375485
CFTR	7.31	EC50	49	nM	CHEMBL_ACT_25905914
CFTR	7.22	EC50	60	nM	CHEMBL_ACT_29226428
CFTR	7.17	EC50	68	nM	CHEMBL_ACT_24375510
CFTR	7.16	EC50	70	nM	CHEMBL_ACT_24375496
CFTR	7	EC50	100	nM	CHEMBL_ACT_25500438
CFTR	6.9	EC50	126	nM	CHEMBL_ACT_18122033
CFTR	6.88	EC50	131	nM	CHEMBL_ACT_24375504
CFTR	6.88	EC50	131	nM	CHEMBL_ACT_29226425
CFTR	6.63	EC50	236	nM	CHEMBL_ACT_15136289
CFTR	6.63	EC50	236	nM	CHEMBL_ACT_15140382
CFTR	5.89	EC50	1300	nM	CHEMBL_ACT_18122005
ADORA3	5.64	AC50	2300	nM	CHEMBL_ACT_25134068
ADRB3	5.36	AC50	4400	nM	CHEMBL_ACT_25153263
SLC6A2	5.19	AC50	6500	nM	CHEMBL_ACT_25144859

Target pathways

Aggregated over 1 target gene(s): CFTR.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
ABC-family protein mediated transport	1	CFTR
RHO GTPases regulate CFTR trafficking	1	CFTR
Defective CFTR causes cystic fibrosis	1	CFTR
Ub-specific processing proteases	1	CFTR
Cargo recognition for clathrin-mediated endocytosis	1	CFTR
Clathrin-mediated endocytosis	1	CFTR
RHOQ GTPase cycle	1	CFTR
Chaperone Mediated Autophagy	1	CFTR
Late endosomal microautophagy	1	CFTR
Aggrephagy	1	CFTR
Developmental Lineage of Pancreatic Ductal Cells	1	CFTR

Dominant GO biological processes

GO term	Targets
cholesterol biosynthetic process	1
water transport	1
bicarbonate transport	1
cholesterol transport	1
response to endoplasmic reticulum stress	1
transepithelial water transport	1
sperm capacitation	1
multicellular organismal-level water homeostasis	1
intracellular pH elevation	1
establishment of localization in cell	1
transmembrane transport	1
membrane hyperpolarization	1
positive regulation of enamel mineralization	1
cellular response to cAMP	1
amelogenesis	1

Indications & clinical

Indications

7 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
respiratory system disorder	4	MONDO:0005087	EFO:0000684
cystic fibrosis	4	MONDO:0009061	MONDO:0009061
chronic obstructive pulmonary disease	2	MONDO:0005002	EFO:0000341
chronic bronchitis	2	MONDO:0005607	EFO:0006505
primary ciliary dyskinesia	2	MONDO:0016575	MONDO:0016575
liver disorder	1	MONDO:0005154	EFO:0001421
sinusitis	0	MONDO:0005961	EFO:0007486

Clinical trials

Total trials: 72.

Phase distribution

Phase	Trials
PHASE3	22
PHASE2	16
PHASE1	14
Not specified	13
PHASE4	5
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07148739	PHASE4	RECRUITING	Ensuring Access to Optimal Therapy in CF: The ENACT Study
NCT01937325	PHASE4	UNKNOWN	CPET in CF Patients With One G551D Mutation Taking VX770
NCT03251911	PHASE4	WITHDRAWN	VX-770 for the Treatment of Chronic Bronchitis
NCT03256799	PHASE4	COMPLETED	Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations
NCT03624101	PHASE4	TERMINATED	Novel Therapeutic Approaches for Treatment of CF Patients With W1282X Premature Termination Codon Mutations
NCT00909532	PHASE3	COMPLETED	Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation
NCT00909727	PHASE3	COMPLETED	Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation
NCT01117012	PHASE3	COMPLETED	Rollover Study of VX-770 in Cystic Fibrosis Subjects
NCT01614457	PHASE3	COMPLETED	Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT)
NCT01614470	PHASE3	COMPLETED	Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) Gating Mutation
NCT01705145	PHASE3	COMPLETED	Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation
NCT01707290	PHASE3	COMPLETED	Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation
NCT01807923	PHASE3	COMPLETED	A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation
NCT01807949	PHASE3	COMPLETED	A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation
NCT01897233	PHASE3	COMPLETED	Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
NCT01931839	PHASE3	COMPLETED	A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis
NCT01946412	PHASE3	COMPLETED	Roll-Over Study of Ivacaftor in Cystic Fibrosis Pediatric Subjects With a CF Transmembrane Conductance Regulator Gene (CFTR) Gating Mutation
NCT02347657	PHASE3	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor
NCT02390219	PHASE3	COMPLETED	Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease
NCT02392234	PHASE3	COMPLETED	A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation
NCT02412111	PHASE3	COMPLETED	A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor
NCT02514473	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation
NCT02516410	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation
NCT02742519	PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating Mutation
NCT02934698	PHASE3	COMPLETED	An Efficacy and Safety Study of Ivacaftor in Patients With Cystic Fibrosis and Two Splicing Mutations
NCT03068312	PHASE3	COMPLETED	A Study to Evaluate Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Have a 3849 + 10KB C→T or D1152H CFTR Mutation
NCT03150719	PHASE3	COMPLETED	A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
NCT06237335	PHASE2	RECRUITING	A Phase 2 Study Evaluating Safety and Tolerability of RCT2100 (CFTR mRNA) in Healthy Participants and in Participants With CF
NCT00457821	PHASE2	COMPLETED	Safety Study of Ivacaftor in Subjects With Cystic Fibrosis
NCT00953706	PHASE2	TERMINATED	Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation
NCT01161537	PHASE2	COMPLETED	Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation
NCT01225211	PHASE2	COMPLETED	Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation
NCT01262352	PHASE2	COMPLETED	Study of the Effect of Ivacaftor on Lung Clearance Index in Subjects With Cystic Fibrosis and the G551D Mutation
NCT01531673	PHASE2	COMPLETED	Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation
NCT01685801	PHASE2	COMPLETED	Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function
NCT02070744	PHASE2	COMPLETED	Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion
NCT02508207	PHASE2	COMPLETED	A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
NCT02730208	PHASE2	COMPLETED	A Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT03085485	PHASE2	COMPLETED	The Topic Trial - Study to Determine the Safety and Efficacy of Ivacaftor

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for ivacaftor and CFTR	CPIC	CFTR		yes
Annotation of CFF Guideline for ivacaftor and CFTR	CFF	CFTR		yes

PharmGKB also curates 58 clinical and 157 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

14 molecules share ≥1 primary target. Top 14 by shared-target count:

Molecule	Source	Status	Shared targets
ELEXACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
GLYBURIDE	ChEMBL	Phase 4 (approved)	CFTR
LUMACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
TEZACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
BAMOCAFTOR	ChEMBL	Phase 3	CFTR
QUERCETIN	ChEMBL	Phase 3	CFTR
RUTIN	ChEMBL	Phase 3	CFTR
GALICAFTOR	ChEMBL	Phase 2	CFTR
GENISTEIN	ChEMBL	Phase 2	CFTR
GLPG-2737	ChEMBL	Phase 2	CFTR
ICENTICAFTOR	ChEMBL	Phase 2	CFTR
NAVOCAFTOR	ChEMBL	Phase 2	CFTR
RISELCAFTOR	ChEMBL	Phase 2	CFTR
Tadalafil	PubChem	Approved	CFTR