Salmeterol

Summary

Salmeterol (CHEMBL1263) is an approved small molecule (ATC R03AC12) targeting ADRB2; indicated across 8 conditions including obstructive lung disease and chronic obstructive pulmonary disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R03AC12
• Targets: 1 (ADRB2)
• Indications: 8 conditions
• Clinical trials: 173
• Chemistry: 415.6 Da · C25H37NO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1263
Name	Salmeterol
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5152
ChEBI	CHEBI:64064
ATC	R03AC12
Molecular formula	C25H37NO4
Molecular weight	415.6
InChIKey	GIIZNNXWQWCKIB-UHFFFAOYSA-N

SMILES: C1=CC=C(C=C1)CCCCOCCCCCCNCC(C2=CC(=C(C=C2)O)CO)O

IUPAC name: 2-(hydroxymethyl)-4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl]phenol

ChEBI definition: A phenol having a hydroxymethyl group at C-2 and a 1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl group at C-4; derivative of phenylethanolamine.

Also known as: GR 33343 X, Salmaterol, Salmeterol, SN408D, Salmeterole, salmeterol, SID26719802, Salmetrol, SALMETEROL, SID144207133, (+/-)-Salmeterol, rac-salmeterol

Parent form; salt/anhydrous children: CHEMBL1082607, CHEMBL3126379

Patent coverage: 9,536 distinct patent families (40,383 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 40,296 (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
ADRB2	β2-adrenoceptor	Partial agonist	9.9	0.4%	P07550

Broader ChEMBL bioactivity targets: 34 (assay-derived). Sample: Lysine-specific demethylase 4E, Nuclear receptor ROR-gamma, 4’-phosphopantetheinyl transferase ffp, Ferritin light chain, 5-hydroxytryptamine receptor 2B, 5-hydroxytryptamine receptor 1B, Alpha-2B adrenergic receptor, 5-hydroxytryptamine receptor 1D, Muscarinic acetylcholine receptor M5, Beta-2 adrenergic receptor.

Bioactivity

ChEMBL activities: 114 potent at pChembl ≥ 5 of 123 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADRB2	10.35	EC50	0.04	nM	CHEMBL_ACT_20628463
ADRB2	10.15	EC50	0.07	nM	CHEMBL_ACT_1900018
ADRB2	10.15	EC50	0.07	nM	CHEMBL_ACT_1990258
ADRB2	10.15	EC50	0.07	nM	CHEMBL_ACT_3436736
ADRB2	10.14	EC50	0.07	nM	CHEMBL_ACT_25928967
ADRB2	10.11	EC50	0.08	nM	CHEMBL_ACT_18988264
ADRB2	10.1	EC50	0.08	nM	CHEMBL_ACT_19232365
ADRB2	9.9	EC50	0.13	nM	CHEMBL_ACT_19232298
ADRB2	9.87	EC50	0.13	nM	CHEMBL_ACT_23306535
ADRB2	9.74	Ki	0.18	nM	CHEMBL_ACT_16581632
ADRB2	9.6	EC50	0.25	nM	CHEMBL_ACT_13952719
ADRB2	9.6	Ki	0.25	nM	CHEMBL_ACT_19232427
ADRB2	9.6	EC50	0.25	nM	CHEMBL_ACT_2420455
ADRB2	9.6	EC50	0.25	nM	CHEMBL_ACT_3303962
ADRB2	9.6	EC50	0.25	nM	CHEMBL_ACT_6308428
ADRB2	9.6	EC50	0.25	nM	CHEMBL_ACT_6385055
ADRB2	9.52	Kd	0.3	nM	CHEMBL_ACT_19403985
ADRB2	9.5	EC50	0.32	nM	CHEMBL_ACT_14710604
ADRB2	9.5	EC50	0.32	nM	CHEMBL_ACT_15030925
ADRB2	9.5	EC50	0.32	nM	CHEMBL_ACT_8007830
ADRB2	9.49	EC50	0.32	nM	CHEMBL_ACT_3294068
ADRB2	9.48	EC50	0.33	nM	CHEMBL_ACT_5238456
ADRB2	9.41	Ki	0.39	nM	CHEMBL_ACT_3294069
ADRB2	9.3	EC50	0.5	nM	CHEMBL_ACT_14712824
ADRB2	9.3	EC50	0.5	nM	CHEMBL_ACT_15030965
ADRB2	9.3	EC50	0.5	nM	CHEMBL_ACT_8007858
ADRB2	9.15	EC50	0.71	nM	CHEMBL_ACT_23194854
ADRB2	9.1	EC50	0.79	nM	CHEMBL_ACT_19232425
ADRB2	9.1	EC50	0.79	nM	CHEMBL_ACT_6284213
ADRB2	9.1	EC50	0.79	nM	CHEMBL_ACT_6292042

Target pathways

Aggregated over 1 target gene(s): ADRB2.

Top Reactome pathways

16 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	ADRB2
Membrane Trafficking	1	ADRB2
Signaling by GPCR	1	ADRB2
Class A/1 (Rhodopsin-like receptors)	1	ADRB2
Amine ligand-binding receptors	1	ADRB2
GPCR downstream signalling	1	ADRB2
Adrenoceptors	1	ADRB2
Metabolism of proteins	1	ADRB2
G alpha (s) signalling events	1	ADRB2
GPCR ligand binding	1	ADRB2
Vesicle-mediated transport	1	ADRB2
Deubiquitination	1	ADRB2
Ub-specific processing proteases	1	ADRB2
Post-translational protein modification	1	ADRB2
Cargo recognition for clathrin-mediated endocytosis	1	ADRB2
Clathrin-mediated endocytosis	1	ADRB2

Dominant GO biological processes

GO term	Targets
diet induced thermogenesis	1
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	1
regulation of sodium ion transport	1
transcription by RNA polymerase II	1
receptor-mediated endocytosis	1
smooth muscle contraction	1
cell surface receptor signaling pathway	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
endosome to lysosome transport	1
response to cold	1
positive regulation of cardiac muscle cell apoptotic process	1
negative regulation of cardiac muscle cell apoptotic process	1
positive regulation of bone mineralization	1
heat generation	1
negative regulation of multicellular organism growth	1

Indications & clinical

Indications

8 indications (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
obstructive lung disease	4	MONDO:0002267	HP:0006536
chronic obstructive pulmonary disease	3	MONDO:0005002	EFO:0000341
pulmonary emphysema	3	MONDO:0004849	EFO:0000464
chronic bronchitis	3	MONDO:0005607	EFO:0006505
asthma	3	MONDO:0004979	MONDO:0004979
bronchiolitis obliterans syndrome	3	MONDO:0015265	EFO:0007183
lung disorder	2	MONDO:0005275	EFO:0003818
spinal cord injury	1	MONDO:0043797	MONDO:0043797

Clinical trials

Total trials: 173.

Phase distribution

Phase	Trials
PHASE4	56
PHASE3	56
Not specified	26
PHASE2	22
PHASE1	13

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00102882	PHASE4	COMPLETED	Study Of Asthma And Genetics In Patients To Be Treated With Fluticasone Propionate/Salmeterol Or Salmeterol Xinafoate
NCT00115492	PHASE4	COMPLETED	Advair® DISKUS® Versus Serevent® DISKUS® For Chronic Obstructive Pulmonary Disease Exacerbations
NCT00118690	PHASE4	COMPLETED	A Study Measuring Asthma Control In Pediatric And Adolescent Subjects Whose Asthma Is Worsened By Activity Or Exercise
NCT00118716	PHASE4	COMPLETED	A Study Measuring Asthma Control In Pediatric And Adolescent Subjects Whose Asthma Is Worsened By Activity Or Exercise
NCT00144911	PHASE4	COMPLETED	ADVAIR® DISKUS® Inhaler (Fluticasone Propionate/Salmeterol) Versus SEREVENT® DISKUS® Inhaler (Salmeterol) For The Treatment Of Chronic Obstructive Pulmonary Disease Exacerbations. ADVAIR® DISKUS® Inhaler and SEREVENT® DISKUS® Inhaler Are Trademarks of the GSK Group of Companies.
NCT00169546	PHASE4	COMPLETED	Study In Airway Physiology In Children SERETIDE DISKUS ® Inhlaer and FLIXOTIDE® Inhaler Are Trademarks of GSK Group of Companies.
NCT00197106	PHASE4	COMPLETED	Treatment Of Symptomatic Asthma In Children
NCT00291382	PHASE4	COMPLETED	Airway Hyper-responsiveness Study In Asthma Using Salmeterol/Fluticasone Propionate Combination Product
NCT00296530	PHASE4	COMPLETED	Study Of Patients With Allergic Rhinitis And Asthma
NCT00315744	PHASE4	COMPLETED	Viapaed Study In Children And Adolescents With Asthma
NCT00327353	PHASE4	COMPLETED	Influence Of Different Airflow Resistances On Drug Effect Of 50μg Salmeterol And 6 μg Formoterol
NCT00346749	PHASE4	TERMINATED	ADVAIR DISKUS® (Fluticasone Propionate/Salmeterol) Inhaler Versus SEREVENT DISKUS® (Salmeterol) Inhlaer On Inflammatory Cells And Markers In Chronic Obstructive Pulmonary Disease. ADVAIR DISKUS® and SEREVENT DISKUS® Inhalers Are Trademarks of the GSK Group of Companies.
NCT00351143	PHASE4	COMPLETED	A Comparative Study To Determine If Motivating Asthma Education (Compliance Enhancement) Has An Effect On Asthma Control
NCT00353873	PHASE4	COMPLETED	Seretide Versus Flixotide In Asthmatic Children Not Controlled By Inhaled Corticosteroids
NCT00355342	PHASE4	COMPLETED	Bone Mineral Density Study In Patients With Chronic Obstructive Pulmonary Disease. DISKUS® Inhaler is a Trademark of the GSK Group of Companies.
NCT00358358	PHASE4	COMPLETED	Chronic Obstructive Pulmonary Disease Endpoints Study
NCT00363480	PHASE4	COMPLETED	Results Of Patient Rated Asthma Control Test In Comparison To Diary Card Data
NCT00370591	PHASE4	COMPLETED	Study Of Airway Physiology In Adults. SERETIDE DISKUS® Inhaler and FLIXOTIDE® Inhaler Are Trademarks of GSK Croup of Companies.
NCT00379028	PHASE4	COMPLETED	Airway Clearance Study
NCT00471809	PHASE4	TERMINATED	Childhood Asthma Research and Education (CARE) Network Trial - Montelukast or Azithromycin for Reduction of Inhaled Corticosteroids in Childhood Asthma (MARS)
NCT00479739	PHASE4	COMPLETED	CONCEPT: A 1-Year Comparison Of A Stable Dose Of SERETIDE® Inhaler With An Adjustable Maintenance Dose Of SYMBICORT® Inhaler. SERETIDE® Inhaler is a Trademark of GSK Group of Companies. SYMBICORT® Inhaler is a Trademark of Astra Zeneca.
NCT00480649	PHASE4	COMPLETED	Successful Control and Clinical Effectiveness Of SERETIDE(Salmeterol/Fluticasone Propionate) Study In Asthma.(SUCCESS)
NCT00503009	PHASE4	TERMINATED	Study Of RV-39 In Patients Who Also Have Asthma
NCT00527826	PHASE4	COMPLETED	Influence Of Salmeterol Xinafoate/Fluticasone Propionate (50/500 µg BID) On The Course Of The Disease And Exacerbation Frequency In COPD Patients Gold Stage III And IV
NCT00530842	PHASE4	COMPLETED	Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD
NCT00563381	PHASE4	COMPLETED	Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients.
NCT00712335	PHASE4	COMPLETED	The Effects of Montelukast on Smokers With Asthma
NCT00784550	PHASE4	COMPLETED	A 24-Week Study to Evaluate the Safety and Efficacy of ADVAIR DISKUS® Inhaler 250/50mcg Plus SPIRIVA HANDIHALER® Inhaler Versus SPIRIVA HANDIHALER® Inhaler Plus Placebo DISKUS® Inhaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD).
NCT00830505	PHASE4	COMPLETED	Fluticasone/Salmeterol (FP/SM) Versus Double the Dose Fluticasone (FP) in Patients With Mild to Moderate Asthma
NCT00914901	PHASE4	UNKNOWN	Concentrations of Salmeterol in Blood and Urine
NCT00984659	PHASE4	COMPLETED	Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease
NCT01131806	PHASE4	UNKNOWN	Comparing Treatment Efficacy With HD/MD Flu Plus Sal in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT01186653	PHASE4	COMPLETED	Effect on Adrenal Function of Budesonide Versus Fluticasone in Chronic Obstructive Pulmonary Disease (COPD)
NCT01243788	PHASE4	UNKNOWN	The Efficacy and Safety of Salmeterol/Fluticasone Propionate vs Atropium/Albuterol in Patients COPD
NCT01255579	PHASE4	COMPLETED	Effects on Small Airways of Two Long-term Extrafine Treatments in Asthma
NCT01361984	PHASE4	UNKNOWN	Sunovion Brovana Versus Serevent Inspiratory Capacity High Resolution Computed Tomography
NCT01388595	PHASE4	COMPLETED	Fluticasone and Salmeterol in Allergic Rhinitis
NCT01526161	PHASE4	COMPLETED	Management of Asthma in School-age Children on Therapy
NCT01536587	PHASE4	COMPLETED	Effects of Salmeterol on Autonomic Nervous System
NCT01555138	PHASE4	COMPLETED	Comparison of Indacaterol 150 mcg Once Daily (o.d.) With Salmeterol/Fluticasone Propionate 50 mcg/500 mcg Twice Daily (b.i.d.)

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 12 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.

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

Molecule	Source	Status	Shared targets
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	ADRB2
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRB2
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRB2
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRB2
ACEBUTOLOL	ChEMBL	Phase 4 (approved)	ADRB2
ADENOSINE	ChEMBL	Phase 4 (approved)	ADRB2
ALBUTEROL	ChEMBL	Phase 4 (approved)	ADRB2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB2
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRB2
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRB2
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	ADRB2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB2
ATENOLOL	ChEMBL	Phase 4 (approved)	ADRB2
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRB2
BETAXOLOL	ChEMBL	Phase 4 (approved)	ADRB2
BISOPROLOL	ChEMBL	Phase 4 (approved)	ADRB2
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB2
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRB2
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRB2
CARTEOLOL	ChEMBL	Phase 4 (approved)	ADRB2
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRB2
CELIPROLOL	ChEMBL	Phase 4 (approved)	ADRB2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRB2
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRB2
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRB2
CLOZAPINE	ChEMBL	Phase 4 (approved)	ADRB2
DARIFENACIN	ChEMBL	Phase 4 (approved)	ADRB2
DEXAMETHASONE	ChEMBL	Phase 4 (approved)	ADRB2
DIPIVEFRIN	ChEMBL	Phase 4 (approved)	ADRB2
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRB2
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRB2
DOPAMINE	ChEMBL	Phase 4 (approved)	ADRB2
DOXAZOSIN	ChEMBL	Phase 4 (approved)	ADRB2
ELAGOLIX	ChEMBL	Phase 4 (approved)	ADRB2
EPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRB2
EPINEPHRINE BITARTRATE	ChEMBL	Phase 4 (approved)	ADRB2
ERGOTAMINE	ChEMBL	Phase 4 (approved)	ADRB2
ESMOLOL	ChEMBL	Phase 4 (approved)	ADRB2
FENOTEROL	ChEMBL	Phase 4 (approved)	ADRB2
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	ADRB2
FORMOTEROL	ChEMBL	Phase 4 (approved)	ADRB2
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRB2
INDACATEROL	ChEMBL	Phase 4 (approved)	ADRB2
ISOETHARINE	ChEMBL	Phase 4 (approved)	ADRB2
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	ADRB2
LABETALOL	ChEMBL	Phase 4 (approved)	ADRB2
LEVOBUNOLOL	ChEMBL	Phase 4 (approved)	ADRB2
LEVOSALBUTAMOL	ChEMBL	Phase 4 (approved)	ADRB2
LOFEPRAMINE	ChEMBL	Phase 4 (approved)	ADRB2
LOPERAMIDE	ChEMBL	Phase 4 (approved)	ADRB2
LOXAPINE	ChEMBL	Phase 4 (approved)	ADRB2
MEBEVERINE	ChEMBL	Phase 4 (approved)	ADRB2
METAPROTERENOL	ChEMBL	Phase 4 (approved)	ADRB2
METOPROLOL	ChEMBL	Phase 4 (approved)	ADRB2
MIFEPRISTONE	ChEMBL	Phase 4 (approved)	ADRB2
MONTELUKAST	ChEMBL	Phase 4 (approved)	ADRB2
NADOLOL	ChEMBL	Phase 4 (approved)	ADRB2
NEBIVOLOL	ChEMBL	Phase 4 (approved)	ADRB2
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	ADRB2