Vanzacaftor

Summary

Vanzacaftor (CHEMBL5314934) 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: 9
• Chemistry: 617.8 Da · C32H39N7O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5314934
Name	Vanzacaftor
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	139399801
Molecular formula	C32H39N7O4S
Molecular weight	617.8
InChIKey	VCSUIBJKYCVWNF-NRFANRHFSA-N

SMILES: CC1(C[C@@H]2CCCNC3=NC(=CC=C3)S(=O)(=O)NC(=O)C4=C(N1C2)N=C(C=C4)N5C=CC(=N5)OCCC6C7(C68CC8)CC7)C

IUPAC name: (14S)-8-[3-(2-dispiro[2.0.24.13]heptan-7-ylethoxy)pyrazol-1-yl]-12,12-dimethyl-2,2-dioxo-2lambda6-thia-3,9,11,18,23-pentazatetracyclo[17.3.1.111,14.05,10]tetracosa-1(22),5(10),6,8,19(23),20-hexaen-4-one

Also known as: Vanzacaftor, Vanzacaftor component of alyftrek, Vx-121, VX-121, VANZACAFTOR

Parent form; salt/anhydrous children: CHEMBL6068396

Patent coverage: 8 distinct patent families (20 SureChEMBL compound mentions), from 1 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			0.1%	P13569

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

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 (0 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	2	MONDO:0009061	MONDO:0009061

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	4
PHASE1	3
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05422222	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age
NCT05444257	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy
NCT05033080	PHASE3	COMPLETED	A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)
NCT05076149	PHASE3	COMPLETED	A Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive (TCR) CFTR Mutation and No F508del Mutation
NCT03768089	PHASE1/PHASE2	COMPLETED	Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis
NCT03912233	PHASE2	COMPLETED	A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis
NCT05437120	PHASE1	COMPLETED	Pharmacokinetics and Safety Assessment of VX-121/Tezacaftor/Deutivacaftor in Participants With Moderate Hepatic Impairment
NCT05535959	PHASE1	COMPLETED	A Study to Evaluate the Relative Bioavailability of a Fixed-dose Combination Tablet of VX-121/Tezacaftor/Deutivacaftor
NCT05867147	PHASE1	COMPLETED	An Electrocardiogram Study to Evaluate the Effect of Vanzacaftor on the QT/QTc Interval in Healthy Participants

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 2 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.

15 molecules share ≥1 primary target. Top 15 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
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