Zafirlukast

Summary

Zafirlukast (CHEMBL603) is an approved small-molecule anti-asthmatic agent (ATC R03DC01) targeting CYSLTR1, CYSLTR2, and EPHX2; indicated across 5 conditions including obstructive lung disease and asthma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R03DC01
• Targets: 4 (CYSLTR1, CYSLTR2, EPHX2…)
• Indications: 5 conditions
• Clinical trials: 4
• Chemistry: 575.7 Da · C31H33N3O6S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL603
Name	Zafirlukast
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5717
ChEBI	CHEBI:10100
ATC	R03DC01
Molecular formula	C31H33N3O6S
Molecular weight	575.7
InChIKey	YEEZWCHGZNKEEK-UHFFFAOYSA-N

SMILES: CC1=CC=CC=C1S(=O)(=O)NC(=O)C2=CC(=C(C=C2)CC3=CN(C4=C3C=C(C=C4)NC(=O)OC5CCCC5)C)OC

IUPAC name: cyclopentyl N-[3-[[2-methoxy-4-[(2-methylphenyl)sulfonylcarbamoyl]phenyl]methyl]-1-methylindol-5-yl]carbamate

Pharmacological roles (ChEBI): anti-asthmatic agent, leukotriene antagonist.

Also known as: Accolate, ICI 204,219, Ici-204,219, ICI-204219, Zafirlukast, SID26719823, SID26757966, SID49681658, ZAFIRLUKAST, zafirlukast, SID170464673, SID144205729

Patent coverage: 5,423 distinct patent families (23,220 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 23,131 (100%) of the total. 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
CYSLTR1	CysLT1 receptor	Antagonist	7.7	0.2%	Q9Y271
CYSLTR2	CysLT2 receptor	Antagonist	5.13	0.1%	Q9NS75
EPHX2	epoxide hydrolase 2	Inhibition	5.7	0%	P34913
PPARG	Peroxisome proliferator-activated receptor-γ	Agonist	5.61	2.6%	P37231

Broader ChEMBL bioactivity targets: 50 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Microtubule-associated protein tau, Streptokinase A, Nuclear receptor ROR-gamma, ATP-dependent DNA helicase Q1, Solute carrier family 22 member 2, Multidrug and toxin extrusion protein 1, Multidrug and toxin extrusion protein 2, ATP-binding cassette sub-family C member 4, Cysteinyl leukotriene receptor 1.

Bioactivity

ChEMBL activities: 57 potent at pChembl ≥ 5 of 83 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYSLTR1	9.59	IC50	0.26	nM	CHEMBL_ACT_24792885
CYSLTR2	9.52	Ki	0.3	nM	CHEMBL_ACT_117165
Q2NNR5	9.52	Ki	0.3	nM	CHEMBL_ACT_128750
Q2NNR5	9.52	Ki	0.3	nM	CHEMBL_ACT_159098
Q2NNR5	9.52	Ki	0.3	nM	CHEMBL_ACT_18067140
Q2NNR5	9.52	Ki	0.3	nM	CHEMBL_ACT_396771
Q2NNR5	9.47	Ki	0.34	nM	CHEMBL_ACT_402928
Q2NNR5	9.36	IC50	0.44	nM	CHEMBL_ACT_1084328
CYSLTR1	9.06	Ki	0.86	nM	CHEMBL_ACT_7782474
CYSLTR1	8.76	IC50	1.73	nM	CHEMBL_ACT_7782473
CYSLTR1	8.74	IC50	1.8	nM	CHEMBL_ACT_18067148
CYSLTR1	8.72	IC50	1.9	nM	CHEMBL_ACT_15657849
Q2NNR5	8.7	IC50	2	nM	CHEMBL_ACT_1251334
CYSLTR2	8.7	Ki	2	nM	CHEMBL_ACT_137946
Q2NNR5	8.7	Ki	2	nM	CHEMBL_ACT_424093
Q2NNR5	8.7	Ki	2	nM	CHEMBL_ACT_824069
Q2NNR5	8.64	Ki	2.3	nM	CHEMBL_ACT_442267
CYSLTR2	8.3	IC50	5	nM	CHEMBL_ACT_1247575
CYSLTR1	7.85	IC50	14	nM	CHEMBL_ACT_16606797
Q2NNR5	7.36	IC50	44	nM	CHEMBL_ACT_1247576
MAPK14	6.45	IC50	353	nM	CHEMBL_ACT_7782547
NR1I2	6.38	AC50	420.6	nM	CHEMBL_ACT_25188500
MAPK1	6.27	IC50	538	nM	CHEMBL_ACT_7782545
NR1I2	6.15	EC50	710	nM	CHEMBL_ACT_15465516
ADORA3	6.11	Ki	770	nM	CHEMBL_ACT_7781681
SLC47A1	5.89	IC50	1300	nM	CHEMBL_ACT_12637852
ADORA3	5.87	IC50	1363	nM	CHEMBL_ACT_7781680
EPHX2	5.7	IC50	2000	nM	CHEMBL_ACT_18709660
EPHX2	5.7	IC50	2000	nM	CHEMBL_ACT_25009609
P10520	5.69	EC50	2050	nM	CHEMBL_ACT_4893633

Target pathways

Aggregated over 4 target gene(s): CYSLTR1, CYSLTR2, EPHX2, PPARG.

Top Reactome pathways

16 total, by targets touching each:

Pathway	Targets	Genes
Leukotriene receptors	2	CYSLTR1, CYSLTR2
G alpha (q) signalling events	2	CYSLTR1, CYSLTR2
LTC4-CYSLTR mediated IL4 production	2	CYSLTR1, CYSLTR2
PPARA activates gene expression	1	PPARG
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	EPHX2
Transcriptional regulation of white adipocyte differentiation	1	PPARG
Nuclear Receptor transcription pathway	1	PPARG
SUMOylation of intracellular receptors	1	PPARG
G alpha (s) signalling events	1	CYSLTR2
Regulation of PTEN gene transcription	1	PPARG
Biosynthesis of maresins	1	EPHX2
MECP2 regulates transcription factors	1	PPARG
Peroxisomal protein import	1	EPHX2
Potential therapeutics for SARS	1	CYSLTR1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	PPARG
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	PPARG

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	3
neuropeptide signaling pathway	2
signal transduction	2
leukotriene signaling pathway	2
positive regulation of gene expression	2
inflammatory response to antigenic stimulus	1
endothelium development	1
calcium ion transport	1
chemotaxis	1
defense response	1
cell surface receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
respiratory gaseous exchange by respiratory system	1
establishment of localization in cell	1
reactive oxygen species biosynthetic process	1

Indications & clinical

Indications

5 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
obstructive lung disease	4	MONDO:0002267	HP:0006536
asthma	4	MONDO:0004979	MONDO:0004979
breast neoplasm	2	MONDO:0021100	MONDO:0007254
ovarian cancer	2	MONDO:0008170	MONDO:0008170
allergic disease	2	MONDO:0005271	MONDO:0005271

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
PHASE2	3
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06069063	PHASE2	NOT_YET_RECRUITING	Crossover Study of Zafirlukast in Preventing Allergen-induced Signs and Symptoms in Response to Cat Dander Challenge
NCT02950480	PHASE2	TERMINATED	Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
NCT04339140	PHASE2	COMPLETED	Zafirlukast in Treatment of Marker Relapsed Ovarian Cancer
NCT01283061	PHASE1	COMPLETED	Bioequivalence Study of Zafirlukast Tablets 20 mg of Dr. Reddy’s Laboratories Limited Under Fasting Condition

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 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.

108 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
MONTELUKAST	ChEMBL	Phase 4 (approved)	CYSLTR1, CYSLTR2, PPARG
FULVESTRANT	ChEMBL + PubChem	Phase 4 (approved)	EPHX2, PPARG
PRANLUKAST	ChEMBL	Phase 4 (approved)	CYSLTR1, CYSLTR2
QUERCETIN	ChEMBL	Phase 3	EPHX2, PPARG
GEMILUKAST	ChEMBL	Phase 2	CYSLTR1, CYSLTR2
POBILUKAST	ChEMBL	Phase 2	CYSLTR1, CYSLTR2
RITOLUKAST	ChEMBL	Phase 2	CYSLTR1, CYSLTR2
TOMELUKAST	ChEMBL	Phase 2	CYSLTR1, CYSLTR2
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	EPHX2
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PPARG
BEXAROTENE	ChEMBL	Phase 4 (approved)	PPARG
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PPARG
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PPARG
CARVEDILOL	ChEMBL	Phase 4 (approved)	PPARG
CEFAMANDOLE	ChEMBL	Phase 4 (approved)	PPARG
CEFOTAXIME	ChEMBL	Phase 4 (approved)	PPARG
CEFOXITIN	ChEMBL	Phase 4 (approved)	PPARG
CEFTAZIDIME	ChEMBL	Phase 4 (approved)	PPARG
CEFTRIAXONE	ChEMBL	Phase 4 (approved)	PPARG
CLOBETASOL PROPIONATE	ChEMBL	Phase 4 (approved)	PPARG
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	CYSLTR1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	CYSLTR1
EFAVIRENZ	ChEMBL	Phase 4 (approved)	PPARG
ELAFIBRANOR	ChEMBL	Phase 4 (approved)	PPARG
FENOFIBRATE	ChEMBL	Phase 4 (approved)	PPARG
FENOFIBRIC ACID	ChEMBL	Phase 4 (approved)	PPARG
GEMFIBROZIL	ChEMBL	Phase 4 (approved)	PPARG
GLYBURIDE	ChEMBL	Phase 4 (approved)	PPARG
INDOMETHACIN	ChEMBL	Phase 4 (approved)	PPARG
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	PPARG
LEVOTHYROXINE	ChEMBL	Phase 4 (approved)	PPARG
LIOTHYRONINE	ChEMBL	Phase 4 (approved)	PPARG
LUMIRACOXIB	ChEMBL	Phase 4 (approved)	PPARG
MASOPROCOL	ChEMBL	Phase 4 (approved)	PPARG
METHYLENE BLUE	ChEMBL	Phase 4 (approved)	PPARG
NINTEDANIB	ChEMBL	Phase 4 (approved)	PPARG
OXAPROZIN	ChEMBL	Phase 4 (approved)	EPHX2
PEMAFIBRATE	ChEMBL	Phase 4 (approved)	PPARG
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	PPARG
RIMONABANT	ChEMBL	Phase 4 (approved)	PPARG
ROSIGLITAZONE	ChEMBL	Phase 4 (approved)	PPARG
SORAFENIB	ChEMBL	Phase 4 (approved)	EPHX2
SULINDAC	ChEMBL	Phase 4 (approved)	PPARG
TELMISARTAN	ChEMBL	Phase 4 (approved)	PPARG
TERIFLUNOMIDE	ChEMBL	Phase 4 (approved)	PPARG
TIPRANAVIR	ChEMBL	Phase 4 (approved)	PPARG
TROGLITAZONE	ChEMBL	Phase 4 (approved)	PPARG
ZILEUTON	ChEMBL	Phase 4 (approved)	EPHX2
ALEGLITAZAR	ChEMBL	Phase 3	PPARG
BALAGLITAZONE	ChEMBL	Phase 3	PPARG
BEZAFIBRATE	ChEMBL	Phase 3	PPARG
CANDESARTAN	ChEMBL	Phase 3	PPARG
DOCONEXENT	ChEMBL	Phase 3	PPARG
EBSELEN	ChEMBL	Phase 3	EPHX2
GAMOLENIC ACID	ChEMBL	Phase 3	PPARG
ICOSAPENT	ChEMBL	Phase 3	PPARG
IMIGLITAZAR	ChEMBL	Phase 3	PPARG
LANIFIBRANOR	ChEMBL	Phase 3	PPARG
LERIGLITAZONE	ChEMBL	Phase 3	PPARG
LOBEGLITAZONE	ChEMBL	Phase 3	PPARG