Eplerenone

Summary

Eplerenone (CHEMBL1095097) is an approved small-molecule antihypertensive agent (ATC C03DA04) targeting NR3C2; indicated across 16 conditions including heart failure and hypertensive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C03DA04
• Targets: 1 (NR3C2)
• Indications: 16 conditions
• Clinical trials: 96
• Chemistry: 414.5 Da · C24H30O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1095097
Name	Eplerenone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	443872
ChEBI	CHEBI:31547
ATC	C03DA04
Molecular formula	C24H30O6
Molecular weight	414.5
InChIKey	JUKPWJGBANNWMW-VWBFHTRKSA-N

SMILES: C[C@]12CCC(=O)C=C1C[C@H]([C@@H]3[C@]24[C@H](O4)C[C@]5([C@H]3CC[C@@]56CCC(=O)O6)C)C(=O)OC

IUPAC name: methyl (1R,2S,9R,10R,11S,14R,15S,17R)-2,15-dimethyl-5,5’-dioxospiro[18-oxapentacyclo[8.8.0.01,17.02,7.011,15]octadec-6-ene-14,2’-oxolane]-9-carboxylate

Pharmacological roles (ChEBI): antihypertensive agent.

Also known as: Eplerenona, Eplerenone, Inspra, SC-66110, SC-6611O, eplerenone, EPLERENONE, SID26754514, SID170465283, SID144205299

Patent coverage: 3,384 distinct patent families (13,067 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
NR3C2	Mineralocorticoid receptor	Antagonist	6.4	0%	P08235

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Androgen receptor, Mineralocorticoid receptor, Glucocorticoid receptor, Progesterone receptor, Mineralocorticoid receptor.

Bioactivity

ChEMBL activities: 21 potent at pChembl ≥ 5 of 26 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P22199	7.4	IC50	39.81	nM	CHEMBL_ACT_19363555
P22199	7.35	Ki	44.4	nM	CHEMBL_ACT_24808022
NR3C2	7.2	IC50	63.1	nM	CHEMBL_ACT_19363569
NR3C2	7	EC50	100	nM	CHEMBL_ACT_19363579
NR3C2	6.91	IC50	122	nM	CHEMBL_ACT_14658162
NR3C2	6.91	IC50	122	nM	CHEMBL_ACT_3403390
NR3C2	6.91	IC50	122	nM	CHEMBL_ACT_3403528
NR3C2	6.9	Ki	125.9	nM	CHEMBL_ACT_19363324
NR3C2	6.87	IC50	135	nM	CHEMBL_ACT_3285844
NR3C2	6.75	IC50	178	nM	CHEMBL_ACT_24808081
NR3C2	6.65	IC50	226	nM	CHEMBL_ACT_24808038
NR3C2	6.62	IC50	240	nM	CHEMBL_ACT_13393480
NR3C2	6.61	IC50	244	nM	CHEMBL_ACT_14566206
NR3C2	6.61	IC50	244	nM	CHEMBL_ACT_22825221
NR3C2	6.4	IC50	398.1	nM	CHEMBL_ACT_19363542
NR3C2	6.1	IC50	794.3	nM	CHEMBL_ACT_19363453
NR3C2	5.89	IC50	1300	nM	CHEMBL_ACT_15099907
NR3C2	5.89	IC50	1300	nM	CHEMBL_ACT_7970233
NR3C2	5.58	IC50	2600	nM	CHEMBL_ACT_15095259
NR3C2	5.58	IC50	2600	nM	CHEMBL_ACT_7970152
NR3C1	5.5	Ki	3162	nM	CHEMBL_ACT_19363404

Target pathways

Aggregated over 1 target gene(s): NR3C2.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Cellular responses to stress	1	NR3C2
SUMOylation	1	NR3C2
SUMO E3 ligases SUMOylate target proteins	1	NR3C2
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	NR3C2
Nuclear Receptor transcription pathway	1	NR3C2
Metabolism of proteins	1	NR3C2
SUMOylation of intracellular receptors	1	NR3C2
Post-translational protein modification	1	NR3C2
Cellular responses to stimuli	1	NR3C2

Dominant GO biological processes

GO term	Targets
regulation of transcription by RNA polymerase II	1
signal transduction	1
nuclear receptor-mediated steroid hormone signaling pathway	1
positive regulation of non-canonical NF-kappaB signal transduction	1
regulation of DNA-templated transcription	1
cellular response to hormone stimulus	1
response to lipid	1

Indications & clinical

Indications

16 indications (6 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
heart failure	4	MONDO:0005252	EFO:0003144
hypertensive disorder	4	MONDO:0005044	EFO:0000537
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
congestive heart failure	4	MONDO:0005009	EFO:0000373
myocardial infarction	4	MONDO:0005068	EFO:0000612
stroke disorder	4	MONDO:0005098	EFO:0000712
cardiomyopathy	3	MONDO:0004994	EFO:0000318
chronic kidney disease	3	MONDO:0005300	EFO:0003884
essential hypertension	3	MONDO:0001134	MONDO:0001134
Duchenne muscular dystrophy	3	MONDO:0010679	MONDO:0010679
diabetic kidney disease	2	MONDO:0005016	EFO:0000401
atrial fibrillation	2	MONDO:0004981	EFO:0000275
primary hyperparathyroidism	2	MONDO:0010837	EFO:0008519
central serous chorioretinopathy	2	MONDO:0018616	EFO:0009784
breast neoplasm	2	MONDO:0021100	MONDO:0007254
type 2 diabetes mellitus	1	MONDO:0005148	MONDO:0005148

Clinical trials

Total trials: 96.

Phase distribution

Phase	Trials
PHASE4	32
PHASE2	18
Not specified	18
PHASE3	13
PHASE1	9
PHASE2/PHASE3	3
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03984591	PHASE4	ENROLLING_BY_INVITATION	A Registry-based Cluster Randomized Trial to Compare the Effect of Spironolactone vs. Eplerenone on Clinical Outcomes in Patients With Symptomatic Systolic Heart Failure
NCT04840342	PHASE4	ACTIVE_NOT_RECRUITING	MR Antagonist and LSD1
NCT05030545	PHASE4	RECRUITING	Cardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study
NCT05593055	PHASE4	RECRUITING	Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension
NCT06168994	PHASE4	NOT_YET_RECRUITING	Role of Eplerenone in Reducing Recurrence of Atrial Fibrillation in Patient With Structural Heart Disease
NCT00082589	PHASE4	COMPLETED	The Purpose of This Study is to Determine if Eplerenone is Effective in Treatment of Mild to Moderate Heart Failure
NCT00108251	PHASE4	COMPLETED	Aldosterone Antagonism in Diastolic Heart Failure
NCT00132093	PHASE4	COMPLETED	Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack
NCT00147563	PHASE4	COMPLETED	Compare Effectiveness of Eplerenone vs Atenolol in Reversing the Remodelling Resistance Arteries in Subjects With HT
NCT00187889	PHASE4	COMPLETED	EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
NCT00293150	PHASE4	TERMINATED	Reversing Endothelial and Diastolic Dysfunction and Improving Collagen Turnover in Diastolic Heart Failure
NCT00391846	PHASE4	COMPLETED	Evaluation of Heart Failure Treatment Guided by N-terminal Pro B-type Natriuretic Peptide (NTproBNP) vs Clinical Symptoms and Signs Alone
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00430924	PHASE4	COMPLETED	Inhibition of Aldosterone in Patients With Chronic Renal Disease
NCT00515021	PHASE4	COMPLETED	Diurnal Variation of Plasminogen Activator Inhibitor-1
NCT00553722	PHASE4	UNKNOWN	Does Aldosterone Cause Hypertension by a Non-Renal Mechanism?
NCT00608465	PHASE4	TERMINATED	Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity
NCT00703352	PHASE4	COMPLETED	Eplerenone in Systemic Right Ventricle
NCT01176968	PHASE4	COMPLETED	Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction
NCT01275352	PHASE4	WITHDRAWN	CLCNKA (Ka Renal Chloride Channel[ClC-Ka]) Polymorphism Effects on Hypertrophy Regression
NCT01302236	PHASE4	WITHDRAWN	Effect of Eplerenone in Elderly Hypertensive Early Stage Chronic Kidney Disease (CKD) Patients
NCT01794091	PHASE4	WITHDRAWN	Detection of Diffuse Scar in Patients With Diabetes
NCT01837108	PHASE4	COMPLETED	Eplerenone and Extracellular Adenosine Formation
NCT01887119	PHASE4	TERMINATED	Aldosterone Antagonism and Microvascular Function
NCT01893788	PHASE4	UNKNOWN	Eplerenone and Aliskiren Research Targeting Hypertensive Patients With Left Ventricular Hypertrophy
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT02345590	PHASE4	UNKNOWN	Eplerenone in the Management of Abdominal Aortic Aneurysms
NCT02462499	PHASE4	COMPLETED	Eplerenone Treatment for Chronic Central Serous Chorioretinopathy in Hungarian Population
NCT02809963	PHASE4	COMPLETED	Mineralocorticoid Receptor Antagonists in Type 2 Diabetes
NCT03079141	PHASE4	UNKNOWN	Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy
NCT04519164	PHASE4	COMPLETED	Aldosterone, the Mineralocorticoid Receptor, and Cardiovascular Disease in Obesity
NCT04746495	PHASE4	WITHDRAWN	Effect of Eplerenone on Novel Biomarkers of Mineralocorticoid Receptor Activation (ENOVA)
NCT02490904	PHASE3	ACTIVE_NOT_RECRUITING	Eplerenone in Patients Undergoing REnal Transplant (EPURE TRANSPLANT)
NCT04450953	PHASE3	RECRUITING	The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients.
NCT00138944	PHASE3	COMPLETED	Effectiveness of Eplerenone to Improve Target Organ Damage in Patients With Resistant Arterial Hypertension
NCT00147589	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Eplerenone in the Treatment of Hypertension in Children.
NCT00147615	PHASE3	COMPLETED	The Long-term Study to Evaluate the Safety of Eplerenone in the Treatment of Hypertension in Children Aged 6 to 16 Years
NCT00232180	PHASE3	COMPLETED	A Comparison Of Outcomes In Patients In New York Heart Association (NYHA) Class II Heart Failure When Treated With Eplerenone Or Placebo In Addition To Standard Heart Failure Medicines
NCT01100203	PHASE3	TERMINATED	Aldosterone Blockade in Chronic Kidney Disease: Influence on Arterial Stiffness and Kidney Function
NCT01115855	PHASE3	COMPLETED	Clinical Study Of Eplerenone In Japanese Patients With Chronic Heart Failure

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.

25 molecules share ≥1 primary target. Top 25 by shared-target count:

Molecule	Source	Status	Shared targets
BUDESONIDE	ChEMBL	Phase 4 (approved)	NR3C2
DEXAMETHASONE	ChEMBL	Phase 4 (approved)	NR3C2
FINERENONE	ChEMBL	Phase 4 (approved)	NR3C2
FLUTICASONE FUROATE	ChEMBL	Phase 4 (approved)	NR3C2
FLUTICASONE PROPIONATE	ChEMBL	Phase 4 (approved)	NR3C2
HYDROCORTISONE	ChEMBL	Phase 4 (approved)	NR3C2
HYDROCORTISONE BUTYRATE	ChEMBL	Phase 4 (approved)	NR3C2
MEDROXYPROGESTERONE	ChEMBL	Phase 4 (approved)	NR3C2
MIFEPRISTONE	ChEMBL	Phase 4 (approved)	NR3C2
PREDNISOLONE	ChEMBL	Phase 4 (approved)	NR3C2
PROGESTERONE	ChEMBL	Phase 4 (approved)	NR3C2
SPIRONOLACTONE	ChEMBL	Phase 4 (approved)	NR3C2
ASOPRISNIL	ChEMBL	Phase 3	NR3C2
BALCINRENONE	ChEMBL	Phase 3	NR3C2
CORTICOSTERONE	ChEMBL	Phase 3	NR3C2
ALDOSTERONE	ChEMBL	Phase 2	NR3C2
LY2623091	ChEMBL	Phase 2	NR3C2
METRIBOLONE	ChEMBL	Phase 2	NR3C2
MT-3995	ChEMBL	Phase 2	NR3C2
ONAPRISTONE	ChEMBL	Phase 2	NR3C2
STANOLONE	ChEMBL	Phase 2	NR3C2
TUROFEXORATE ISOPROPYL	ChEMBL	Phase 2	NR3C2
Enzalutamide	PubChem	Approved	NR3C2
Fludrocortisone	PubChem	Approved	NR3C2
ursodiol	PubChem	Approved	NR3C2