Ivabradine

Summary

Ivabradine (CHEMBL471737) is an approved small-molecule cardiotonic drug (ATC C01EB17) targeting HCN1, HCN2, and HCN3; indicated across 21 conditions including cardiovascular disorder and heart failure.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01EB17
• Targets: 4 (HCN1, HCN2, HCN3…)
• Indications: 21 conditions
• Clinical trials: 81
• Chemistry: 468.6 Da · C27H36N2O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL471737
Name	Ivabradine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	132999
ChEBI	CHEBI:85966
ATC	C01EB17
Molecular formula	C27H36N2O5
Molecular weight	468.6
InChIKey	ACRHBAYQBXXRTO-OAQYLSRUSA-N

SMILES: CN(CCCN1CCC2=CC(=C(C=C2CC1=O)OC)OC)C[C@H]3CC4=CC(=C(C=C34)OC)OC

IUPAC name: 3-[3-[[(7S)-3,4-dimethoxy-7-bicyclo[4.2.0]octa-1,3,5-trienyl]methyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one

ChEBI definition: A member of the class of benzazepines that is 7,8-dimethoxy-1,3,4,5-tetrahydro-3-benzazepin-2-one in which the amide hydrogen is replaced by a [{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino]propyl} group. Used (as its hydrochloride salt) to treat patients with angina who have intolerance to beta blockers and/or heart failure.

Pharmacological roles (ChEBI): cardiotonic drug.

Also known as: Ivabradina, Ivabradine, S-16257, ivabradine, IVABRADINE, Ivabradine hydrochlorideÊ, Ivabradine hydrochlorideÂ, IVABRADINE HYDROCHLORIDE, Ivabradine HCl (Procoralan)

Parent form; salt/anhydrous children: CHEMBL2145077

Patent coverage: 890 distinct patent families (2,989 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 2,917 (98%) 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
HCN1	HCN1	Antagonist	5.7	0%	O60741
HCN2	HCN2	Antagonist	5.6	4.2%	Q9UL51
HCN3	HCN3	Antagonist	5.7	0%	Q9P1Z3
HCN4	HCN4	Antagonist	5.7	0.1%	Q9Y3Q4

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1, Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2, Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4, Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A, Sodium-dependent serotonin transporter, D(3) dopamine receptor, Voltage-gated inwardly rectifying potassium channel KCNH2.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DRD3	5.58	AC50	2613	nM	CHEMBL_ACT_25195117
CHRM2	5.47	AC50	3352	nM	CHEMBL_ACT_25196349
HCN4	5.37	EC50	4280	nM	CHEMBL_ACT_3464818
O88704	5.35	EC50	4500	nM	CHEMBL_ACT_3464773
O88703	5.34	EC50	4520	nM	CHEMBL_ACT_3464801
HTR1A	5.24	AC50	5807	nM	CHEMBL_ACT_25165637

Target pathways

Aggregated over 4 target gene(s): HCN1, HCN2, HCN3, HCN4.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
HCN channels	4	HCN1, HCN2, HCN3, HCN4

Dominant GO biological processes

GO term	Targets
regulation of membrane depolarization	4
sodium ion transmembrane transport	4
regulation of membrane potential	4
cellular response to cAMP	4
potassium ion transmembrane transport	4
sodium ion import across plasma membrane	4
potassium ion import across plasma membrane	4
monoatomic ion transport	4
potassium ion transport	4
sodium ion transport	4
monoatomic ion transmembrane transport	4
transmembrane transport	4
regulation of heart rate by cardiac conduction	3
regulation of SA node cell action potential	3
cellular response to cGMP	2

Indications & clinical

Indications

21 indications (3 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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
heart failure	4	MONDO:0005252	EFO:0003144
congestive heart failure	4	MONDO:0005009	EFO:0000373
diabetic kidney disease	3	MONDO:0005016	EFO:0000401
mitral valve stenosis	3	MONDO:0005852	EFO:0007372
atrial fibrillation	3	MONDO:0004981	EFO:0000275
toxic shock syndrome	3	MONDO:0001881	EFO:0006834
coronary artery disorder	3	MONDO:0005010	EFO:0001645
postural orthostatic tachycardia syndrome	3	MONDO:0011479	EFO:1000645
neoplasm	3	MONDO:0005070	MONDO:0004992
orthostatic hypotension	2	MONDO:0005469	EFO:0005252
diastolic heart failure	2	MONDO:0006727	EFO:1000899
lymphoma	2	MONDO:0005062	EFO:0000574
systolic heart failure	2	MONDO:0006993	EFO:1001207
multiple organ dysfunction syndrome	2	MONDO:0043726	EFO:1001373
hypotensive disorder	2	MONDO:0005468	EFO:0005251
long COVID-19	2	MONDO:0100233	MONDO:0100233

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

Clinical trials

Total trials: 81.

Phase distribution

Phase	Trials
PHASE4	32
Not specified	18
PHASE3	16
PHASE2	10
PHASE2/PHASE3	2
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05882708	PHASE4	RECRUITING	Effect of Heart Rate Control With Ivabradine on Hemodynamic in Patients With Sepsis
NCT07135258	PHASE4	NOT_YET_RECRUITING	Atrial Fibrillation: In Search for the Optimal Target for Rate Control
NCT00815100	PHASE4	COMPLETED	Effects of the Ivabradine on Reduction of Inflammatory Markers in Patients With Acute Coronary Syndrome
NCT00825123	PHASE4	TERMINATED	Effects of Heart Rate Reduction on Central Arterial Pressure in Healthy Individuals
NCT01029223	PHASE4	WITHDRAWN	The Influence of Heart Rate Reduction Upon Central Arterial Pressure in Younger and Older Healthy Individuals
NCT01364077	PHASE4	UNKNOWN	Ivabradine in Hemodialysed Patients With Increased Heart Rate
NCT01365286	PHASE4	COMPLETED	HR-lowering Efficacy and Respiratory Safety of Ivabradine in Patients With Obstructive Airway Disease
NCT01373619	PHASE4	COMPLETED	Heart Failure With Normal Ejection Fraction (HFNEF) in Hemodialysed Patients: Beneficial Effect of Ivabradine
NCT01425164	PHASE4	UNKNOWN	Ischemia In Hemodialysed Patients: Ivabradine Versus Carvedilol
NCT01699776	PHASE4	COMPLETED	Efficacy Study of Digoxin & Ivabradine to Treat Heart Failure
NCT01755663	PHASE4	UNKNOWN	Comparison of Efficacy of Ivabradine Versus Metoprolol
NCT01768585	PHASE4	UNKNOWN	Study to Investigate the Effect of Heart Rate Reduction With Ivabradine on Vascular Elastic Properties and Endothelial Function in Patients With Stable Coronary Heart Disease
NCT02046044	PHASE4	UNKNOWN	Digoxin Versus Ivabradine in Heart Failure With Reduced Ejection Fraction
NCT02166060	PHASE4	UNKNOWN	Ivabradine in Patients With an Unsatisfactory Percentage of Cardiac Resynchronization Therapy
NCT02507050	PHASE4	WITHDRAWN	Ivabradine and Post-revascularisation Microcirculatory Dysfunction
NCT02681978	PHASE4	COMPLETED	Ivabradine to Improve Endothelial Function in Patients With Coronary Artery Disease
NCT02827500	PHASE4	COMPLETED	Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)
NCT02973594	PHASE4	COMPLETED	Pulse Reduction On Beta-blocker and Ivabradine Therapy
NCT03168529	PHASE4	TERMINATED	Trial Assessing the Effectiveness of Ivabradine Started at Discharge From the Observation Unit
NCT03245996	PHASE4	COMPLETED	The Impact of Heart Rate on Central Blood Pressure in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker
NCT03387605	PHASE4	UNKNOWN	Effect of Ivabradine in Stage D HF/Cardiogenic Shock Patients on Dobutamine
NCT03405831	PHASE4	UNKNOWN	Effect of Ivabradine on Exercise Capacity After Heart Transplantation
NCT03437369	PHASE4	UNKNOWN	Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock
NCT03456856	PHASE4	COMPLETED	A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction.
NCT03631654	PHASE4	WITHDRAWN	Ivabradine in Stage D Heart Failure Patients on Chronic Inotropes
NCT03866395	PHASE4	COMPLETED	Effects of Ivabradine on Residual Myocardial Ischemia After PCI
NCT04436016	PHASE4	COMPLETED	PeRiOperaTivE CardioproTection With Ivabradine in Non-cardiac Surgery
NCT04448899	PHASE4	COMPLETED	Ivabradine in Patients With Congestive Heart Failure
NCT05261464	PHASE4	UNKNOWN	Heart Rate Controller in Computed Tomography Coronary Angiography
NCT05348057	PHASE4	UNKNOWN	Clinical Study of CMR to Evaluate the Effect of Ivabradine on the Improvement of Left Ventricular Remodeling in STEMI Patients After Primary PCI
NCT05481177	PHASE4	UNKNOWN	Ivabradine for Long-Term Effects of COVID-19 With POTS Cohort
NCT06371222	PHASE4	COMPLETED	Role of Ivabradine on Heart Rate and Quality of Life in Patients With Mitral Stenosis in Sinus Rhythm
NCT04031573	PHASE3	ACTIVE_NOT_RECRUITING	Ivabradine for Heart Rate Control In Septic Shock
NCT05279651	PHASE3	ACTIVE_NOT_RECRUITING	Ivabradine for Prevention of Myocardial Injury After Noncardiac Surgery Trial (PREVENT-MINS)
NCT07268170	PHASE2/PHASE3	ENROLLING_BY_INVITATION	Heart Rate Control Before Cardiac Computed Tomography in Adults for the Evaluation of Coronary Artery Disease
NCT00143507	PHASE3	COMPLETED	The BEAUTIFUL Study: Effects of Ivabradine in Patients With Stable Coronary Artery Disease and Left Ventricular Systolic Dysfunction
NCT00202566	PHASE3	COMPLETED	Efficacy and Safety of Ivabradine on Top of Atenolol in Stable Angina Pectoris
NCT01022463	PHASE3	COMPLETED	Effect of Ivabradine on Heart Rate & Effort Tolerance in Mitral Stenosis in Sinus Rhythm
NCT01178528	PHASE3	COMPLETED	Heart Rate Reduction in Heart Failure
NCT01657136	PHASE3	COMPLETED	Ivabradine Versus Beta-blockers in the Treatment of Inappropriate Sinus Tachycardia

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.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
Propafenone	PubChem	Approved	HCN2, HCN4
ZATEBRADINE	ChEMBL	Phase 2	HCN4
Belzutifan	PubChem	Approved	HCN4
Zuranolone	PubChem	Approved	HCN2