Tezacaftor

Summary

Tezacaftor (CHEMBL3544914) is an approved small molecule targeting CFTR; indicated across 1 condition including cystic fibrosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (CFTR)
• Indications: 1 condition
• Clinical trials: 18
• Chemistry: 520.5 Da · C26H27F3N2O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3544914
Name	Tezacaftor
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	46199646
Molecular formula	C26H27F3N2O6
Molecular weight	520.5
InChIKey	MJUVRTYWUMPBTR-MRXNPFEDSA-N

SMILES: CC(C)(CO)C1=CC2=CC(=C(C=C2N1C[C@H](CO)O)F)NC(=O)C3(CC3)C4=CC5=C(C=C4)OC(O5)(F)F

IUPAC name: 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-[1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide

Also known as: Tezacaftor, Tezacaftor component of symkevi, Tezacaftor component of trikafta, VX-661, TEZACAFTOR, tezacaftor, US10022352, Compound 315

Patent coverage: 496 distinct patent families (1,466 SureChEMBL compound mentions), from 3 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		6.57	0.1%	P13569

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Sodium channel protein type 5 subunit alpha, 5-hydroxytryptamine receptor 2A, 3’,5’-cyclic-AMP phosphodiesterase 4D, Cystic fibrosis transmembrane conductance regulator.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 7 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CFTR	6.57	EC50	272	nM	CHEMBL_ACT_16880867
CFTR	6.57	EC50	272	nM	CHEMBL_ACT_26906343
CFTR	6.3	EC50	500	nM	CHEMBL_ACT_29226433
CFTR	5.96	EC50	1100	nM	CHEMBL_ACT_25905923
PDE4D	5.06	AC50	8700	nM	CHEMBL_ACT_25185444

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

1 indication (1 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
cystic fibrosis	4	MONDO:0009061	MONDO:0009061

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
Not specified	6
PHASE2	5
PHASE3	3
PHASE1	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07148739	PHASE4	RECRUITING	Ensuring Access to Optimal Therapy in CF: The ENACT Study
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
NCT03150719	PHASE3	COMPLETED	A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
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
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
NCT04006873	PHASE2	COMPLETED	Gut Imaging for Function & Transit in Cystic Fibrosis Study 2
NCT06154447	PHASE1	ACTIVE_NOT_RECRUITING	Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis
NCT02015507	PHASE1	COMPLETED	An Open-Label, Phase 1 Study in Healthy Adult Subjects to Examine the Effects of Multiple-Dose Ciprofloxacin on Ivacaftor and VX-661 in Combination With Ivacaftor
NCT03029455	PHASE1	COMPLETED	A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
NCT04509050	Not specified	RECRUITING	Study to Evaluate Biological & Clinical Effects of Significantly Corrected CFTR Function in Infants & Young Children
NCT06191640	Not specified	RECRUITING	Sinus Disease in Young Children With Cystic Fibrosis
NCT07363304	Not specified	RECRUITING	Impact of Elexacaftor-Tezacaftor-Ivacaftor Treatment on Metabolic, Epigenetic and Fecal Microbiota Profiles in People With Cystic Fibrosis.
NCT03278314	Not specified	APPROVED_FOR_MARKETING	Tezacaftor/Ivacaftor Combination Therapy Expanded Access Program for Patients 12 Years of Age and Older With Cystic Fibrosis
NCT05576324	Not specified	UNKNOWN	Effect of the CFTR-modulating Triple Therapy Elexacaftor - Tezacaftor - Ivacaftor
NCT05699148	Not specified	UNKNOWN	Gut Imaging for Function and Transit in Cystic Fibrosis 3 Junior

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 11 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
IVACAFTOR	ChEMBL + PubChem	Phase 4 (approved)	CFTR
ELEXACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
GLYBURIDE	ChEMBL	Phase 4 (approved)	CFTR
LUMACAFTOR	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