Montelukast

Summary

Montelukast (CHEMBL787) is an approved small-molecule leukotriene antagonist (ATC R03DC53) targeting CYSLTR1 and GPR17; indicated across 30 conditions including obstructive lung disease and allergic rhinitis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R03DC53 (+1 more)
• Targets: 2 (CYSLTR1, GPR17)
• Indications: 30 conditions
• Clinical trials: 260
• Chemistry: 586.2 Da · C35H36ClNO3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL787
Name	Montelukast
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5281040
ChEBI	CHEBI:50730
ATC	R03DC53, R03DC03
Molecular formula	C35H36ClNO3S
Molecular weight	586.2
InChIKey	UCHDWCPVSPXUMX-TZIWLTJVSA-N

SMILES: CC(C)(C1=CC=CC=C1CC[C@H](C2=CC=CC(=C2)/C=C/C3=NC4=C(C=CC(=C4)Cl)C=C3)SCC5(CC5)CC(=O)O)O

IUPAC name: 2-[1-[[(1R)-1-[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid

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

Also known as: Brondilat, Montelukast, Singulair, montelukast, Montelukast (cingulair), MONTELUKAST, MONTELUKAST SODIUM

Parent form; salt/anhydrous children: CHEMBL1200681

Patent coverage: 6,764 distinct patent families (26,700 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 26,579 (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	8.64	0.2%	Q9Y271
GPR17	GPR17	Antagonist	7.21	1.6%	Q13304

Broader ChEMBL bioactivity targets: 33 (assay-derived). Sample: Uracil nucleotide/cysteinyl leukotriene receptor, Cysteinyl leukotriene receptor 1, 5-hydroxytryptamine receptor 2B, Thromboxane-A synthase, Tyrosine-protein kinase Fyn, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Epidermal growth factor receptor, Glucocorticoid receptor.

Bioactivity

ChEMBL activities: 55 potent at pChembl ≥ 5 of 63 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYSLTR2	9.37	IC50	0.43	nM	CHEMBL_ACT_958575
CYSLTR1	9.3	IC50	0.5	nM	CHEMBL_ACT_106797
Q2NNR5	9.3	IC50	0.5	nM	CHEMBL_ACT_1072619
Q2NNR5	9.3	IC50	0.5	nM	CHEMBL_ACT_16742574
Q2NNR5	9.3	Ki	0.5	nM	CHEMBL_ACT_177414
CYSLTR2	9.19	IC50	0.64	nM	CHEMBL_ACT_958574
CYSLTR1	9.11	IC50	0.78	nM	CHEMBL_ACT_958576
CYSLTR1	8.94	Ki	1.14	nM	CHEMBL_ACT_7762852
Q2NNR5	8.68	Ki	2.1	nM	CHEMBL_ACT_582881
CYSLTR1	8.64	IC50	2.3	nM	CHEMBL_ACT_15657848
CYSLTR1	8.64	IC50	2.29	nM	CHEMBL_ACT_7762851
CYP2C8	7.25	IC50	56.5	nM	CHEMBL_ACT_29191723
CYSLTR1	7.14	EC50	72	nM	CHEMBL_ACT_3408489
CYP2C8	6.89	IC50	130	nM	CHEMBL_ACT_24925870
CYP2C8	6.8	IC50	160	nM	CHEMBL_ACT_29116822
ADORA3	6.61	Ki	245	nM	CHEMBL_ACT_7760740
ADORA3	6.36	IC50	434	nM	CHEMBL_ACT_7760739
ADRA2C	6.12	Ki	767	nM	CHEMBL_ACT_7760754
MAPK14	6.07	IC50	856	nM	CHEMBL_ACT_7764923
CYP2C8	6	IC50	1000	nM	CHEMBL_ACT_18125085
CYP2C8	5.9	IC50	1270	nM	CHEMBL_ACT_24366295
ABCB11	5.89	AC50	1300	nM	CHEMBL_ACT_25127092
TACR2	5.89	Ki	1274	nM	CHEMBL_ACT_7764966
CHRM3	5.85	Ki	1404	nM	CHEMBL_ACT_7762868
ADRA2A	5.83	Ki	1470	nM	CHEMBL_ACT_7760750
TBXAS1	5.82	IC50	1525	nM	CHEMBL_ACT_7764969
OPRD1	5.77	Ki	1690	nM	CHEMBL_ACT_7762884
CHRM1	5.71	Ki	1938	nM	CHEMBL_ACT_7762864
PPARG	5.68	AC50	2100	nM	CHEMBL_ACT_25113983
SLC6A3	5.68	Ki	2067	nM	CHEMBL_ACT_7762810

Target pathways

Aggregated over 2 target gene(s): CYSLTR1, GPR17.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Leukotriene receptors	2	CYSLTR1, GPR17
G alpha (q) signalling events	2	CYSLTR1, GPR17
P2Y receptors	1	GPR17
G alpha (i) signalling events	1	GPR17
LTC4-CYSLTR mediated IL4 production	1	CYSLTR1
Potential therapeutics for SARS	1	CYSLTR1

Dominant GO biological processes

GO term	Targets
signal transduction	2
G protein-coupled receptor signaling pathway	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
neuropeptide signaling pathway	1
respiratory gaseous exchange by respiratory system	1
establishment of localization in cell	1
reactive oxygen species biosynthetic process	1
leukotriene signaling pathway	1
negative regulation of inflammatory response to antigenic stimulus	1

Indications & clinical

Indications

30 indications (4 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
allergic rhinitis	4	MONDO:0011786	EFO:0005854
seasonal allergic rhinitis	4	MONDO:0005324	EFO:0003956
asthma	4	MONDO:0004979	MONDO:0004979
perennial allergic rhinitis	3	MONDO:0024332	EFO:1001417
obstructive sleep apnea syndrome	3	MONDO:0007147	EFO:0003918
rheumatoid arthritis	3	MONDO:0008383	EFO:0000685
plasma cell myeloma	3	MONDO:0009693	EFO:0001378
eosinophilic esophagitis	3	MONDO:0005361	EFO:0004232
severe acute respiratory syndrome	3	MONDO:0005091	EFO:0000694
diabetic kidney disease	3	MONDO:0005016	EFO:0000401
acne	3	MONDO:0011438	EFO:0003894
sleep apnea syndrome	2	MONDO:0005296	EFO:0003877
status asthmaticus	2	MONDO:0004766	EFO:0008590
Dengue hemorrhagic fever	2	MONDO:0005358	EFO:0004227
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
sickle cell disease	2	MONDO:0011382	MONDO:0011382
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
Parkinson disease	2	MONDO:0005180	MONDO:0005180
respiratory system disorder	1	MONDO:0005087	EFO:0000684
immune system disorder	1	MONDO:0005046	EFO:0000540
HIV infectious disease	1	MONDO:0005109	EFO:0000764
metabolic dysfunction-associated steatohepatitis	1	MONDO:0007027	EFO:1001249
bronchopulmonary dysplasia	1	MONDO:0019091	MONDO:0019091
persian gulf syndrome	1	MONDO:0005907	EFO:0007430

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 260.

Phase distribution

Phase	Trials
PHASE4	74
PHASE3	61
PHASE2	41
PHASE1	32
Not specified	31
PHASE2/PHASE3	11
EARLY_PHASE1	8
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT05498116	PHASE4	RECRUITING	Effect of Montelukast on Kidney and Vascular Function in Type 1 Diabetes
NCT07101445	PHASE4	RECRUITING	Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial
NCT07532993	PHASE4	NOT_YET_RECRUITING	Comparison of Antihistamine and Antileukotriene Add-On Therapy to Intranasal Corticosteroid in Allergic Rhinitis
NCT00092092	PHASE4	COMPLETED	Study of Montelukast and Its Effect on Lower Leg Growth in Children With Asthma (MK-0476-254)
NCT00119015	PHASE4	TERMINATED	The Addition of Montelukast to Fluticasone in the Treatment of Perennial Allergic Rhinitis
NCT00148408	PHASE4	COMPLETED	Trial of Asthma Patient Education (TAPE)
NCT00156819	PHASE4	COMPLETED	The Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial
NCT00189462	PHASE4	COMPLETED	A Pilot Study to Evaluate the Efficacy of Montelukast in the Treatment of Acute Otitis Media (AOM) in Children
NCT00189475	PHASE4	COMPLETED	Evaluate the Potential of Montelukast to Prevent Nasal Symptomatology During Colds
NCT00196547	PHASE4	COMPLETED	Montelukast in Modulating Exacerbations of Asthma in Children
NCT00273689	PHASE4	COMPLETED	Exercise Induced Bronchospasm in Children
NCT00295022	PHASE4	COMPLETED	Compare the Efficacy of Levocetirizine and Montelukast to Placebo in Reducing Seasonal Allergic Rhinitis (SAR) Symptoms in Ragweed Sensitive Subjects
NCT00296491	PHASE4	COMPLETED	Study Of Allergic Rhinitis In Patients Who Also Have Asthma
NCT00296530	PHASE4	COMPLETED	Study Of Patients With Allergic Rhinitis And Asthma
NCT00299910	PHASE4	UNKNOWN	Inflammatory Response to Anti Inflammatory Therapy in Children With Sleep Disordered Breathing
NCT00351364	PHASE4	TERMINATED	Does Montelukast Have an Affect on the Function of the Artery in Patients With Heart Disease
NCT00380484	PHASE4	COMPLETED	Short- and Long Term Growth in Children With Asthma
NCT00394355	PHASE4	COMPLETED	Effects of Mometasone Furoate Dry Powder Inhaler, Fluticasone Propionate, and Montelukast on Bone Mineral Density in Asthmatics (Study P03418)
NCT00406094	PHASE4	UNKNOWN	Singulair Use in Non-Allergic Rhinitis Eosinophil Syndrome (NARES)
NCT00442559	PHASE4	COMPLETED	Montelukast in Mild Asthmatic Children With Allergic Rhinitis (0476-367)
NCT00453765	PHASE4	COMPLETED	The Effect of Montelukast in Patients With Chronic Cough and Bronchial Hyperreactivity
NCT00471809	PHASE4	TERMINATED	Childhood Asthma Research and Education (CARE) Network Trial - Montelukast or Azithromycin for Reduction of Inhaled Corticosteroids in Childhood Asthma (MARS)
NCT00487773	PHASE4	COMPLETED	Effect of Different Doses of Budesonide on Markers of Bone Metabolism in Children With Asthma
NCT00488176	PHASE4	UNKNOWN	Comparison of the Effect of Montelukast and Cetirizine on Allergic Inflammation in Children With Allergic Rhinitis
NCT00490243	PHASE4	COMPLETED	Effect of Different Anti-Asthmatic Treatments on Lung Function and on Exercise-Induced Bronchoconstriction in Children With Asthma
NCT00545844	PHASE4	COMPLETED	Singulair(R) In Asthma And Allergic Rhinitis (0476-383)
NCT00557284	PHASE4	COMPLETED	Efficacy Study of Montelukast in Atopic Dermatitis Induced by Food Allergens
NCT00559546	PHASE4	COMPLETED	Montelukast as a Controller of Atopic Syndrome
NCT00590772	PHASE4	COMPLETED	The Role of Montelukast in Rhinitis and Sleep
NCT00641472	PHASE4	COMPLETED	Pulmicort Respules(Budesonide Inhalation Suspension) vs Singulair, Children
NCT00712335	PHASE4	COMPLETED	The Effects of Montelukast on Smokers With Asthma
NCT00721240	PHASE4	COMPLETED	Investigation to Identify Predictors of Response to a Treatment With Montelukast
NCT00756418	PHASE4	COMPLETED	Montelukast Post-marketing Comparative Study With Theophyline Added to Inhaled Corticosteroid (0476-396)
NCT00770900	PHASE4	COMPLETED	Study to Evaluate the Inflammatory Cells Activity in Patients With Persistent Asthma Treated With Montelukast (0476-403)(COMPLETED)
NCT00775697	PHASE4	UNKNOWN	Montelukast in Children With Wheezing
NCT00832455	PHASE4	COMPLETED	Pediatric ACTION3 (Identify, Treat, Control): Effectiveness of Adding Montelukast in Pediatric Subjects With Uncontrolled Asthma (0476-385)
NCT00875082	PHASE4	COMPLETED	Effect of Montelukast on Remodelling Markers in Asthmatic Children
NCT00912171	PHASE4	COMPLETED	Efficacy of Oral Leukotriene in Long Term Therapy of Mild and Moderate Obstructive Sleep Apnea Syndrome in Children
NCT00913328	PHASE4	COMPLETED	Effect of Add-on Montelukast to Inhaled Corticosteroids on Airway Responsiveness

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 15 clinical and 23 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.

17 molecules share ≥1 primary target. Top 17 by shared-target count:

Molecule	Source	Status	Shared targets
PRANLUKAST	ChEMBL	Phase 4 (approved)	CYSLTR1, GPR17
INDOMETHACIN	ChEMBL + PubChem	Phase 4 (approved)	GPR17
CANGRELOR TETRASODIUM	ChEMBL	Phase 4 (approved)	GPR17
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	CYSLTR1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	CYSLTR1
ZAFIRLUKAST	ChEMBL	Phase 4 (approved)	CYSLTR1
ABLUKAST	ChEMBL	Phase 2	CYSLTR1
GAVESTINEL	ChEMBL	Phase 2	GPR17
GEMILUKAST	ChEMBL	Phase 2	CYSLTR1
POBILUKAST	ChEMBL	Phase 2	CYSLTR1
RITOLUKAST	ChEMBL	Phase 2	CYSLTR1
TOMELUKAST	ChEMBL	Phase 2	CYSLTR1
VERLUKAST	ChEMBL	Phase 2	CYSLTR1
Belzutifan	PubChem	Approved	CYSLTR1
Rizatriptan	PubChem	Approved	GPR17
tryptophan	PubChem	Approved	GPR17
Zileuton	PubChem	Approved	GPR17