Nicorandil

Summary

Nicorandil (CHEMBL284906) is an approved small-molecule vasodilator agent (ATC C01DX16) targeting KCNJ8 and KCNJ11; indicated across 8 conditions including cardiovascular disorder and myocardial infarction.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01DX16
• Targets: 2 (KCNJ8, KCNJ11)
• Indications: 8 conditions
• Clinical trials: 27
• Chemistry: 211.17 Da · C8H9N3O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL284906
Name	Nicorandil
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	47528
ChEBI	CHEBI:31905
ATC	C01DX16
Molecular formula	C8H9N3O4
Molecular weight	211.17
InChIKey	LBHIOVVIQHSOQN-UHFFFAOYSA-N

SMILES: C1=CC(=CN=C1)C(=O)NCCO[N+](=O)[O-]

IUPAC name: 2-(pyridine-3-carbonylamino)ethyl nitrate

ChEBI definition: A pyrimidinecarboxamide that is nicotinamide in which one of the hydrogens attached to the carboxamide nitrogen is replaced by a 2-(nitrooxy)ethyl group. It has both nitrate-like and ATP-sensitive potassium channel activator properties, and is used for the prevention and treatment of angina pectoris.

Pharmacological roles (ChEBI): vasodilator agent, potassium channel opener.

Also known as: Ikorel, Nicorandil, SG-75, Sigmart, SID11114278, SID26719873, SID85148372, NICORANDIL, SID144204519, SID170465582, C0164866, nicorandil

Patent coverage: 2,430 distinct patent families (8,672 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 8,663 (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
KCNJ8	Kir6.1	Agonist		0%	Q15842
KCNJ11	Kir6.2			0.1%	Q14654

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Menin/Histone-lysine N-methyltransferase MLL, Polyunsaturated fatty acid lipoxygenase ALOX15, Cytochrome P450 2C9, Cytochrome P450 2C19, 3-hydroxyacyl-CoA dehydrogenase type-2, Lethal factor.

Bioactivity

ChEMBL activities: 4 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
CYP2C9	5.7	Potency	1995	nM	CHEMBL_ACT_5029479
CYP2C9	5.7	AC50	1995	nM	CHEMBL_ACT_6041588
CYP2C19	5.4	Potency	3981	nM	CHEMBL_ACT_4021431
CYP2C19	5.4	AC50	3981	nM	CHEMBL_ACT_6056527

Target pathways

Aggregated over 2 target gene(s): KCNJ8, KCNJ11.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNJ11, KCNJ8
ATP sensitive Potassium channels	2	KCNJ11, KCNJ8
Inwardly rectifying K+ channels	2	KCNJ11, KCNJ8
Potassium Channels	2	KCNJ11, KCNJ8
Metabolism	1	KCNJ11
Integration of energy metabolism	1	KCNJ11
Disease	1	KCNJ11
Transport of small molecules	1	KCNJ11
ABC-family protein mediated transport	1	KCNJ11
Muscle contraction	1	KCNJ11
Regulation of insulin secretion	1	KCNJ11
Cardiac conduction	1	KCNJ11
Ion homeostasis	1	KCNJ11
ABC transporter disorders	1	KCNJ11
Disorders of transmembrane transporters	1	KCNJ11
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	KCNJ11
Defective ABCC8 can cause hypo- and hyper-glycemias	1	KCNJ11

Dominant GO biological processes

GO term	Targets
response to hypoxia	2
response to ischemia	2
ventricular cardiac muscle tissue development	2
potassium ion transport	2
apoptotic process	2
determination of adult lifespan	2
response to xenobiotic stimulus	2
response to ATP	2
regulation of monoatomic ion transmembrane transport	2
CAMKK-AMPK signaling cascade	2
potassium ion transmembrane transport	2
obsolete inorganic cation transmembrane transport	2
response to resveratrol	2
potassium ion import across plasma membrane	2
action potential	2

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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
myocardial infarction	3	MONDO:0005068	EFO:0000612
severe acute respiratory syndrome	3	MONDO:0005091	MONDO:0100096
dementia	2	MONDO:0001627	HP:0000726
coronary artery disorder	2	MONDO:0005010	EFO:0001645
radiation pneumonitis	2	MONDO:0043919	MONDO:0043919

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

Clinical trials

Total trials: 27.

Phase distribution

Phase	Trials
PHASE4	15
Not specified	5
PHASE2	3
PHASE3	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01475123	PHASE4	ACTIVE_NOT_RECRUITING	Prospective Study of End Stage Renal Disease Patients With Coronary Artery Disease Treated by Oral Nicorandil
NCT05427786	PHASE4	RECRUITING	A Study to Evaluate the Impact of Pre-procedural Intracoronary Nicorandil Injection to PREVENT ReductioN of DecREased TIMI FLOW in Patients Who Undergoing Percutaneous Coronary Intervention for the Coronary Artery Disease
NCT06787430	PHASE4	NOT_YET_RECRUITING	Effects of Nicorandil on Microvascular Dysfunction in Patients With STEMI Undergoing Primary PCI
NCT01185015	PHASE4	WITHDRAWN	A Multi-centric Study to Assess the Efficacy of Sigmart in Subjects With Recurrent Angina After Coronary Revascularization
NCT01396395	PHASE4	COMPLETED	Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina
NCT01397994	PHASE4	UNKNOWN	Study to Assess Efficacy of Nicorandil+Atenolol vs Atenolol in Treatment of Chronic Stable Angina.
NCT02254252	PHASE4	COMPLETED	Effects of Nicorandil on Angina Symptoms in Patients With Coronary Slow Flow
NCT02328521	PHASE4	UNKNOWN	Efficacy Study of Nicorandil on Neointima
NCT02435797	PHASE4	UNKNOWN	Effect of Nicorandil for the Patients of Acute ST Segment Elevation Myocardial Infarction
NCT03010423	PHASE4	TERMINATED	Efficacy Study of Oral Nicorandil on Improving Microvascular Function in Female Non-obstructive Coronary Artery Disease (CAD) Participants
NCT03252665	PHASE4	UNKNOWN	Efficacy of Intracoronary Infusion of Different Medicine in STEMI Patients Undergoing Primary PCI
NCT03445728	PHASE4	COMPLETED	China-Administration of Nicorandil Group（CHANGE）
NCT04665648	PHASE4	COMPLETED	Clinical Efficacy and sAfety of Intravenous Infusion of Nicorandil During Primary Percutaneous Coronary Intervention
NCT04826497	PHASE4	UNKNOWN	Effect of Nicorandil on Cardiac Sympathetic Nerve for the Patients of Acute ST Segment Elevation Myocardial Infarction
NCT05087797	PHASE4	COMPLETED	The Effect of Nicorandil on Left Ventricular Myocardial Strain in Patients With Coronary Chronic Total Occlusion
NCT06423729	PHASE2/PHASE3	RECRUITING	Effect of Nicorandil in Type 2 Diabetic Obese Patients
NCT02449070	PHASE3	UNKNOWN	Effects of Nicorandil on Cardiac Infarct Size in Patients With ST-segment Elevation Acute Myocardial Infarction
NCT04631536	PHASE3	UNKNOWN	Managing Endothelial Dysfunction in COVID-19 : A Randomized Controlled Trial at LAUMC
NCT04120766	PHASE2	ACTIVE_NOT_RECRUITING	Safety and Modulation of ABCC9 Pathways by Nicorandil for the Treatment of Hippocampal Sclerosis of Aging
NCT02809456	PHASE2	UNKNOWN	Mitigation of Radiation Pneumonitis, Fibrosis and Heart Toxicity With Nicorandil in Lung Cancer Patients
NCT05399576	PHASE2	UNKNOWN	Intracoronary of Nicorandil and Verapamil to Reduce the Occurrence of Periprocedural Myocardial Injury
NCT07138508	PHASE1/PHASE2	COMPLETED	Oral Nicorandil for Prevention of No Reflow Phenomenon in Anterior STEMI Patients Undergoing PPCI
NCT00212030	Not specified	COMPLETED	Japan-Working Groups of Acute Myocardial Infarction for the Reduction of Necrotic Damage by a K-ATP
NCT00424801	Not specified	TERMINATED	Effects of Intensive Long-Term Vasodilation in Hypertensive Patients With Microvascular Angina Pectoris
NCT00848562	Not specified	COMPLETED	Nicorandil Study to Reduce Cardiac Death After Percutaneous Coronary Intervention (PCI) in Hemodialysis Patients
NCT03775902	Not specified	COMPLETED	Regulation of KATP Channels and Na+/K+ ATPase in Relation to Fatigue Development
NCT04632121	Not specified	UNKNOWN	Oral Nicorandil in ST Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for chlorpropamide, dabrafenib, gliclazid	CPIC	G6PD

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.

8 molecules share ≥1 primary target. Top 8 by shared-target count:

Molecule	Source	Status	Shared targets
glyburide	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11, KCNJ8
CROMAKALIM	ChEMBL	Phase 2	KCNJ11, KCNJ8
DIAZOXIDE	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11
PROPAFENONE	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11
PINACIDIL	ChEMBL	Phase 4 (approved)	KCNJ11
CLAMIKALANT	ChEMBL	Phase 2	KCNJ11
TIFENAZOXIDE	ChEMBL	Phase 2	KCNJ11
Berberine Chloride	PubChem	Approved	KCNJ11