Tiotropium

Summary

Tiotropium (CHEMBL1900528) is an approved small-molecule muscarinic antagonist targeting CHRM1, CHRM2, and CHRM3; indicated across 5 conditions including chronic obstructive pulmonary disease and asthma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 5 (CHRM1, CHRM2, CHRM3…)
• Indications: 5 conditions
• Clinical trials: 254
• Chemistry: 392.5 Da · C19H22NO4S2+

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1900528
Name	Tiotropium
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	5487427
ChEBI	CHEBI:90960
Molecular formula	C19H22NO4S2+
Molecular weight	392.5
InChIKey	LERNTVKEWCAPOY-FPISHFTHSA-N

SMILES: C[N+]1([C@@H]2CC(C[C@H]1[C@H]3[C@@H]2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C

IUPAC name: [(1S,2S,4R,5R)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonan-7-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate

ChEBI definition: A quaternary ammonium ion obtained by methylation of the tertiary amino group of (1α,2β,4β,5α,7β)-7-[(hydroxydi-2-thienylacetyl)oxy]-9-methyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane. Used (in the form of the bromide hydrate) for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease.

Pharmacological roles (ChEBI): muscarinic antagonist, bronchodilator agent.

Also known as: Tiotropium, Tiotropium cation, Tiotropium ion, SID50113015, tiotropium, SID174006895, TIOTROPIUM, Tiotropium Bromide hydrate, Tiotropium bromide

Parent form; salt/anhydrous children: CHEMBL3545181, CHEMBL4440620

Patent coverage: 33 distinct patent families (57 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
CHRM1	M1 receptor	Antagonist	10.7	0.2%	P11229
CHRM2	M2 receptor	Antagonist	10.7	0%	P08172
CHRM3	M3 receptor	Antagonist	11.1	0%	P20309
CHRM4	M4 receptor	Antagonist	10.6	1.6%	P08173
CHRM5	M5 receptor	Antagonist	10.2	0%	P08912

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Muscarinic acetylcholine receptor M3.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
CHRM3	10.5	Ki	0.03	nM	CHEMBL_ACT_15247964

Target pathways

Aggregated over 5 target gene(s): CHRM1, CHRM2, CHRM3, CHRM4, CHRM5.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Signaling by GPCR	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Class A/1 (Rhodopsin-like receptors)	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Amine ligand-binding receptors	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GPCR downstream signalling	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Muscarinic acetylcholine receptors	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GPCR ligand binding	5	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
G alpha (q) signalling events	3	CHRM1, CHRM3, CHRM5
G alpha (i) signalling events	2	CHRM2, CHRM4
Metabolism	1	CHRM3
Integration of energy metabolism	1	CHRM3
Membrane Trafficking	1	CHRM2
Acetylcholine regulates insulin secretion	1	CHRM3
Regulation of insulin secretion	1	CHRM3
Vesicle-mediated transport	1	CHRM2
Cargo recognition for clathrin-mediated endocytosis	1	CHRM2
Clathrin-mediated endocytosis	1	CHRM2

Dominant GO biological processes

GO term	Targets
signal transduction	5
G protein-coupled receptor signaling pathway	5
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	5
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	5
G protein-coupled acetylcholine receptor signaling pathway	5
chemical synaptic transmission	5
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	3
nervous system development	3
acetylcholine receptor signaling pathway	3
regulation of locomotion	2
saliva secretion	2
regulation of smooth muscle contraction	2
phospholipase C-activating G protein-coupled receptor signaling pathway	1
neuromuscular synaptic transmission	1
positive regulation of monoatomic ion transport	1

Indications & clinical

Indications

5 indications (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
chronic obstructive pulmonary disease	3	MONDO:0005002	EFO:0000341
asthma	3	MONDO:0004979	MONDO:0004979
kidney failure	1	MONDO:0001106	HP:0000083
spinal cord injury	1	MONDO:0043797	MONDO:0043797
chronic bronchitis	0	MONDO:0005607	EFO:0006505

Clinical trials

Total trials: 254.

Phase distribution

Phase	Trials
PHASE3	87
PHASE4	68
PHASE2	38
Not specified	33
PHASE1	23
PHASE1/PHASE2	2
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06679465	PHASE4	NOT_YET_RECRUITING	Evaluating the Impact of Single Dose Tiotropium on Allergen-induced Early Asthmatic Response
NCT00144196	PHASE4	COMPLETED	12 Week Efficacy of Tiotropium Versus Placebo in Patients With Mild COPD According to Swedish Guidelines (SPIRIMILD)
NCT00152984	PHASE4	COMPLETED	Efficacy and Safety of Tiotropium in Patients With COPD and Concomitant Diagnosis of Asthma
NCT00239408	PHASE4	COMPLETED	Spiriva (Tiotropium Bromide) Assessment of FEV1 - (SAFE-Portugal).
NCT00239499	PHASE4	COMPLETED	Pilot Study Comparing Tiotropium (Spiriva) to Salmeterol (Serevent) Plus Fluticasone (Flixotide) in Chronic Obstructive Pulmonary Disease (COPD)
NCT00335621	PHASE4	WITHDRAWN	Replacement of Nebulised Ipratropium With Inhaled Tiotropium in Stable Chronic Obstructive Pulmonary Disease (COPD)
NCT00359788	PHASE4	COMPLETED	A Trial Comparing Treatment With Tiotropium Inhalation Capsules to Combivent Inhalation Aerosol in COPD Patients.
NCT00361959	PHASE4	COMPLETED	SERETIDE 50/500mcg Versus Tiotropium Bromide On Exacerbation Rates In Severe Chronic Obstructive Pulmonary Disease
NCT00388882	PHASE4	COMPLETED	Trial Comparing Treatment With Tiotropium Inhalation Capsules to Combivent® Inhalation Aerosol in COPD Patients.
NCT00394485	PHASE4	TERMINATED	Tiotropium + Procaterol vs Tiotropium + Placebo in COPD Patients
NCT00405236	PHASE4	COMPLETED	Effect of Tiotropium on Inflammation and Exacerbations in COPD
NCT00412204	PHASE4	COMPLETED	Study to Evaluate the Effects of Tiotropium Bromide on Chronic Obstructive Pulmonary Disease (COPD) During Exercise
NCT00424528	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)
NCT00523991	PHASE4	COMPLETED	Trial Comparing Tiotropium Inhalation Capsules vs Placebo in Chronic Obstructive Pulmonary Disease (COPD).
NCT00525512	PHASE4	COMPLETED	Tiotropium In Exercise
NCT00546234	PHASE4	WITHDRAWN	Tiotropium for Smoking Asthmatics Study
NCT00563381	PHASE4	COMPLETED	Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients.
NCT00578968	PHASE4	COMPLETED	Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation
NCT00783250	PHASE4	TERMINATED	Bronchodilators and Respiratory Mechanics in Chronic Obstructive Pulmonary Disease (COPD) Patients
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).
NCT00864812	PHASE4	COMPLETED	Clinical Outcomes of Tiotropium Plus Fluticasone Propionate/Salmeterol Compared With Tiotropium for Chronic Obstructive Pulmonary Disease (COPD) in Korea
NCT00975195	PHASE4	COMPLETED	Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease
NCT01072396	PHASE4	COMPLETED	Effects of Tiotropium on Breathing Capacity and Exercise Limitation in Early Stages of Chronic Obstructive Pulmonary Disease
NCT01307189	PHASE4	COMPLETED	Effects of Tiotropium on Walking Capacity in Patients With COPD
NCT01397890	PHASE4	COMPLETED	Efficacy and Tolerability of Symbicort as an add-on Treatment to Spiriva Compare With Spiriva Alone in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD)
NCT01437748	PHASE4	COMPLETED	Closing Volume Interpretation and Bronchodilators Effect
NCT01455129	PHASE4	COMPLETED	Tiotropium In Early Chronic Obstructive Pulmonary Disease Patients in China
NCT01465906	PHASE4	UNKNOWN	Efficacy and Safety of Tulobuterol Patch Combined With Tiotropium Bromide for Relieving Dyspnea Symptom of Chronic Obstructive Pulmonary Disease
NCT01466712	PHASE4	UNKNOWN	Evaluate the Effects of Formoterol and Beclomethasone Dipropionate Combination Therapy on Small Airways Function
NCT01483625	PHASE4	COMPLETED	Tiotropium (18mcg) in Chronic Obstructive Pulmonary Disease (COPD) Patients With a Respiratory Infection
NCT01656005	PHASE4	COMPLETED	Beta Blocker Therapy in Moderate to Severe COPD
NCT01662986	PHASE4	COMPLETED	Investigate the Impact of Early Treatment Initiation With Tiotropium in Patients Recovering From Hospitalization for an Acute COPD Exacerbation 2
NCT01663987	PHASE4	COMPLETED	Investigate the Impact of Early Treatment Initiation With Tiotropium in Patients Recovering From Hospitalization for an Acute COPD Exacerbation 1
NCT01693003	PHASE4	COMPLETED	Indacaterol Versus Tiotropium on Dynamic Hyperinflation in COPD
NCT01715311	PHASE4	WITHDRAWN	Comparison of Indacaterol With That of Placebo in ‘Maintenance naïve’ Patients With COPD Using Blinded Tiotropium as Active Control
NCT01727024	PHASE4	COMPLETED	Study Evaluating Preference, Satisfaction And Correct Use Of Inhalers In COPD Patients
NCT01751113	PHASE4	COMPLETED	A 3 Way Cross-over Study Evaluating the Effects of ADOAIR Twice Daily Plus Tiotropium Bromide Once Daily Compared With the Individual Treatments of Japanese Subjects
NCT01762800	PHASE4	COMPLETED	Evaluating the Control of COPD Symptoms in Patients Treated With Tiotropium Bromide 18mcg Once Daily Alone, ADOAIR 50/250mcg Twice Daily Alone or ADOAIR 50/250mcg Plus Tiotropium Bromide 18mcg
NCT01922271	PHASE4	COMPLETED	Efficacy of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)
NCT01959516	PHASE4	COMPLETED	Effect of Glycopyrronium on Morning Symptoms and Pulmonary Function in Patients With Moderate to Severe COPD

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

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

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Mavorixafor	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ACETYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
AMIODARONE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
AMOXAPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ATROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
BENZTROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
BETHANECHOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CARBACHOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CARBAMOYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CHLOROQUINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CINNARIZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLEMASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLIDINIUM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CYCLIZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DARIFENACIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DESLORATADINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DEXCHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DICYCLOMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DIPHENIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
DOXEPIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
EBASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
GLYCOPYRRONIUM BROMIDE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
HALOPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
HOMATROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
HYDROXYCHLOROQUINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
IMIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
IPRATROPIUM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
KETOTIFEN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
LOXAPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MAPROTILINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MEPAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
METHSCOPOLAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
METHSCOPOLAMINE BROMIDE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
MIANSERIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
ORPHENADRINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
OXYBUTYNIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PAROXETINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PERHEXILINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PILOCARPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PIRENZEPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PROMAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
PROMETHAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
QUETIAPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
QUINACRINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
RISPERIDONE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
SCOPOLAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
SERTRALINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, CHRM3, CHRM4, CHRM5