Darifenacin

Summary

Darifenacin (CHEMBL1346) is an approved small-molecule muscarinic antagonist (ATC G04BD10) targeting CHRM1 and CHRM3; indicated across 4 conditions including overactive bladder and amyotrophic lateral sclerosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G04BD10
• Targets: 2 (CHRM1, CHRM3)
• Indications: 4 conditions
• Clinical trials: 100
• Chemistry: 426.5 Da · C28H30N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1346
Name	Darifenacin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	444031
ChEBI	CHEBI:391960
ATC	G04BD10
Molecular formula	C28H30N2O2
Molecular weight	426.5
InChIKey	HXGBXQDTNZMWGS-RUZDIDTESA-N

SMILES: C1CN(C[C@@H]1C(C2=CC=CC=C2)(C3=CC=CC=C3)C(=O)N)CCC4=CC5=C(C=C4)OCC5

IUPAC name: 2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide

ChEBI definition: 2-[(3S)-1-Ethylpyrrolidin-3-yl]-2,2-diphenylacetamide in which one of the hydrogens at the 2-position of the ethyl group is substituted by a 2,3-dihydro-1-benzofuran-5-yl group. It is a selective antagonist for the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions, and is used as the hydrobromide salt in the management of urinary incontinence.

Pharmacological roles (ChEBI): muscarinic antagonist, antispasmodic drug.

Also known as: Darifenacin, Darifenacin extended release, Darifenacina, Darifenacine, UK-88525, UK88525, Indacaterol, SID50113277, darifenacin, DARIFENACIN

Parent form; salt/anhydrous children: CHEMBL1200935

Patent coverage: 2,402 distinct patent families (8,259 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 8,258 (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
CHRM1	M1 receptor	Antagonist	8.8	0.2%	P11229
CHRM3	M3 receptor	Antagonist	9.5	0%	P20309

Broader ChEMBL bioactivity targets: 27 (assay-derived). Sample: Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, A-type voltage-gated potassium channel KCND3, Sodium channel protein type 5 subunit alpha, Muscarinic acetylcholine receptor M5, Beta-2 adrenergic receptor.

Bioactivity

ChEMBL activities: 48 potent at pChembl ≥ 5 of 53 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CHRM3	9.13	Ki	0.74	nM	CHEMBL_ACT_20607077
ADRB2	9.1	EC50	0.79	nM	CHEMBL_ACT_15247937
ADRB2	9.09	EC50	0.82	nM	CHEMBL_ACT_5238457
CHRM3	9.08	Ki	0.84	nM	CHEMBL_ACT_1195096
Q8K4Z4	9	EC50	1	nM	CHEMBL_ACT_5238184
CHRM3	8.89	Ki	1.3	nM	CHEMBL_ACT_1666529
ADRB2	8.69	EC50	2.05	nM	CHEMBL_ACT_11004972
CHRM5	8.64	Ki	2.3	nM	CHEMBL_ACT_1195100
P08483	8.6	Ki	2.5	nM	CHEMBL_ACT_2040197
CHRM1	8.26	Ki	5.5	nM	CHEMBL_ACT_1195097
CHRM1	8.26	Ki	5.5	nM	CHEMBL_ACT_20607050
CHRM4	8.07	Ki	8.6	nM	CHEMBL_ACT_1195099
CHRM3	7.96	EC50	11	nM	CHEMBL_ACT_20607256
CHRM2	7.92	Ki	12	nM	CHEMBL_ACT_20607019
ADRB2	7.8	Ki	15.9	nM	CHEMBL_ACT_11004931
CHRM2	7.8	Kd	15.85	nM	CHEMBL_ACT_1666600
ADRB2	7.8	EC50	15.85	nM	CHEMBL_ACT_6292041
CHRM3	7.75	AC50	18	nM	CHEMBL_ACT_25137241
CHRM3	7.5	EC50	32	nM	CHEMBL_ACT_20607251
ADRB1	7.4	EC50	39.81	nM	CHEMBL_ACT_6291290
CHRM3	7.35	EC50	45	nM	CHEMBL_ACT_20607253
CHRM2	7.33	Ki	47	nM	CHEMBL_ACT_1195098
CHRM2	7.3	Ki	50	nM	CHEMBL_ACT_1666565
ADRB2	7.21	Ki	61	nM	CHEMBL_ACT_5238443
P10980	7.2	Ki	63	nM	CHEMBL_ACT_2040198
KCNH2	7.1	IC50	79.43	nM	CHEMBL_ACT_15258073
SLC6A4	7.02	AC50	96	nM	CHEMBL_ACT_25150888
ADRB1	6.75	Ki	180	nM	CHEMBL_ACT_11004941
ADRB1	6.5	IC50	316.2	nM	CHEMBL_ACT_6292030
KCNH2	6.47	AC50	340	nM	CHEMBL_ACT_25118682

Target pathways

Aggregated over 2 target gene(s): CHRM1, CHRM3.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	CHRM1, CHRM3
Signaling by GPCR	2	CHRM1, CHRM3
Class A/1 (Rhodopsin-like receptors)	2	CHRM1, CHRM3
Amine ligand-binding receptors	2	CHRM1, CHRM3
GPCR downstream signalling	2	CHRM1, CHRM3
Muscarinic acetylcholine receptors	2	CHRM1, CHRM3
G alpha (q) signalling events	2	CHRM1, CHRM3
GPCR ligand binding	2	CHRM1, CHRM3
Metabolism	1	CHRM3
Integration of energy metabolism	1	CHRM3
Acetylcholine regulates insulin secretion	1	CHRM3
Regulation of insulin secretion	1	CHRM3

Dominant GO biological processes

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

Indications & clinical

Indications

4 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
overactive bladder	3	MONDO:0006624	EFO:1000781
amyotrophic lateral sclerosis	2	MONDO:0004976	MONDO:0004976

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

Clinical trials

Total trials: 100.

Phase distribution

Phase	Trials
PHASE3	36
PHASE4	25
PHASE2	18
PHASE1	9
Not specified	9
PHASE1/PHASE2	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00127270	PHASE4	COMPLETED	Using Behavioral Therapy in Combination With Darifenacin for Symptoms of Overactive Bladder
NCT00171184	PHASE4	COMPLETED	Efficacy, Safety, and Tolerability of Darifenacin in Patients Aged > 65 Years With Overactive Bladder
NCT00366002	PHASE4	COMPLETED	Patient’s Perception of Treatment Outcome With Darifenacin by Patients With Overactive Bladder
NCT00413790	PHASE4	COMPLETED	Pharmacologic Effects of Darifenacin and Tolterodine on Cardiovascular Parameters in Healthy Subjects
NCT01018225	PHASE4	WITHDRAWN	Exploratory Study Evaluating the Effects of Darifenacin on Nocturia, Sleep and Daytime Wakefulness
NCT01272362	PHASE4	COMPLETED	To Determine the Relationship Between Baseline Reversibility and the Efficacy of Indacaterol
NCT01377428	PHASE4	WITHDRAWN	Efficacy of Indacaterol 150 µg Versus Formoterol
NCT01543828	PHASE4	COMPLETED	Indacaterol 75 μg Compared to Placebo, Assessing Time to Patient’s Perception of Onset of Effect in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
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.)
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
NCT01996124	PHASE4	COMPLETED	Acute Effect of Pulmonary Desufflation on Cardiac Performance in COPD Patients
NCT02039011	PHASE4	COMPLETED	Ultra-long Acting Bronchodilator Therapy in Asthmatics
NCT02055352	PHASE4	COMPLETED	Study to Evaluate Efficacy/Safety of Combination Budesonide/Indacaterol vs Fluticasone/Salmeterol in Patients With COPD
NCT02418468	PHASE4	COMPLETED	Effects of Indacaterol in Symptomatic COPD Patients With Low Risk of Exacerbations
NCT02473237	PHASE4	COMPLETED	Efficacy in Walked Distance of Indacaterol vs Tiotropium in Women With COPD Secondary to Biomass (EMERALD)
NCT02547558	PHASE4	UNKNOWN	Pulmonary Gas Exchange Response to Indacaterol in COPD
NCT02566031	PHASE4	COMPLETED	A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients
NCT02576626	PHASE4	COMPLETED	Single Dose Ultibro Breezhaler by Sd-DPI Versus Ipratropium/Salbutamol by Nebulizer in COPD
NCT02872090	PHASE4	COMPLETED	Effects of Long Acting Bronchodilators on CARDiac Autonomic Control in Chronic Obstructive Pulmonary Disease (COPD)
NCT02953041	PHASE4	COMPLETED	Effect of a LAMA and a uLABA on the Methacholine Dose-response Curve
NCT03364829	PHASE4	UNKNOWN	Utilizing Wearable Device to Observe the Clinical Response of COPD Patients Treated With Combined Bronchodilator and Home-based Pulmonary Rehabilitation Program
NCT05506865	PHASE4	COMPLETED	Efficacy and Safety of Indacaterol vs Tiotropium in Women With COPD Secondary to Biomass Exposure
NCT06616675	PHASE4	COMPLETED	Darifenacin x Parasacral Transcutaneous Electric Nerve Stimulation for OAB in Patients Infected With Human T-Lymphotropic Virus 1
NCT00170755	PHASE3	COMPLETED	A Long-Term Safety, Tolerability and Efficacy Study of Darifenacin in Adult Patients With Overactive Bladder
NCT00171145	PHASE3	COMPLETED	A 12-Week Study to Evaluate the Efficacy of Darifenacin to Increase the Warning Time in Patients With Overactive Bladder.
NCT00393458	PHASE3	COMPLETED	Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control
NCT00463567	PHASE2/PHASE3	COMPLETED	26 Week Efficacy, Safety and Tolerability Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)
NCT00529529	PHASE3	COMPLETED	Safety of Indacaterol in Patients (≥ 12 Years) With Moderate to Severe Persistent Asthma
NCT00567996	PHASE3	COMPLETED	Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) Using Salmeterol as Active Control
NCT00615030	PHASE3	COMPLETED	Study of Indacaterol Dosed in the Evening in Patients With Chronic Obstructive Pulmonary Disease (COPD)
NCT00615459	PHASE3	COMPLETED	A Crossover Study to Determine the Effect on Lung Function of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control
NCT00620022	PHASE3	COMPLETED	The Effect of Indacaterol on Exercise Endurance in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
NCT00622635	PHASE3	COMPLETED	A Crossover Study to Determine the 24 Hour Lung Function Profile of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)
NCT00624286	PHASE3	COMPLETED	Efficacy and Safety of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)
NCT00669617	PHASE3	COMPLETED	Study to Determine the Onset of Action of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
NCT00677807	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Indacaterol in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)
NCT00792805	PHASE3	COMPLETED	Efficacy and Safety of Indacaterol in Adults (40 Years and Above) With Chronic Obstructive Pulmonary Disease (COPD)
NCT00794157	PHASE3	COMPLETED	Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM3
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM3
LINAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM3
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM3
ACETYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
ACETYLCHOLINE CHLORIDE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
AMBENONIUM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
AMIODARONE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
AMOXAPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
AMSACRINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
ANISOTROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
ATROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BENPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BENZTROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BEPRIDIL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BETAMETHASONE PHOSPHORIC ACID	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BETHANECHOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BIPERIDEN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BROMPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CARBACHOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CARBAMOYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CEVIMELINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CHLOROQUINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CINACALCET	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CINNARIZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CLEMASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CLIDINIUM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CLOZAPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CYCLIZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CYCLOPENTOLATE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DESIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DESLORATADINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DEXCHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DICYCLOMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DIPHEMANIL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DIPHENIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DOTHIEPIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
DOXEPIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
EBASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
ECONAZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
EPALRESTAT	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
FEDRATINIB	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
FENTANYL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
FLUOXETINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
GLYCOPYRRONIUM BROMIDE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
HALOPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3
HOMATROPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM3