Eleclazine

Summary

Eleclazine (CHEMBL3707392) is a phase-3 clinical-stage small molecule targeting SCN5A; indicated across 4 conditions including hypertrophic cardiomyopathy and myocardial ischemia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (SCN5A)
• Indications: 4 conditions
• Clinical trials: 10
• Chemistry: 415.4 Da · C21H16F3N3O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3707392
Name	Eleclazine
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	71183216
Molecular formula	C21H16F3N3O3
Molecular weight	415.4
InChIKey	YNUAEEJQYHYLMS-UHFFFAOYSA-N

SMILES: C1COC2=C(C=C(C=C2)C3=CC=C(C=C3)OC(F)(F)F)C(=O)N1CC4=NC=CC=N4

IUPAC name: 4-(pyrimidin-2-ylmethyl)-7-[4-(trifluoromethoxy)phenyl]-2,3-dihydro-1,4-benzoxazepin-5-one

Also known as: Eleclazina, Eleclazine, GS-6615, ELECLAZINE

Parent form; salt/anhydrous children: CHEMBL3972607

Patent coverage: 27 distinct patent families (111 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 69 (62%) 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
SCN5A	Nav1.5	Inhibition		0.2%	Q14524

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Sodium channel protein type 1 subunit alpha, Sodium channel protein type 5 subunit alpha, Sodium channel protein type 4 subunit alpha, Voltage-gated inwardly rectifying potassium channel KCNH2, Sodium channel protein type 2 subunit alpha, Sodium channel protein type 9 subunit alpha, Sodium channel protein type 3 subunit alpha, Sodium channel protein type 8 subunit alpha, Sodium channel protein type 10 subunit alpha.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 27 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SCN5A	7	IC50	100	nM	CHEMBL_ACT_22950109
SCN5A	6.58	IC50	260	nM	CHEMBL_ACT_22950129
SCN5A	6.22	IC50	600	nM	CHEMBL_ACT_16910801
SCN5A	6.22	IC50	600	nM	CHEMBL_ACT_22950108
SCN5A	6.22	IC50	600	nM	CHEMBL_ACT_22950128
SCN9A	6	IC50	1000	nM	CHEMBL_ACT_22950126
SCN9A	5.96	IC50	1100	nM	CHEMBL_ACT_16910769
SCN10A	5.82	IC50	1500	nM	CHEMBL_ACT_16910738
SCN10A	5.82	IC50	1500	nM	CHEMBL_ACT_22950127
SCN4A	5.48	IC50	3300	nM	CHEMBL_ACT_22949981
SCN1A	5.47	IC50	3400	nM	CHEMBL_ACT_16910735
SCN1A	5.47	IC50	3400	nM	CHEMBL_ACT_22950123
SCN3A	5.46	IC50	3500	nM	CHEMBL_ACT_22950125
SCN8A	5.4	IC50	4000	nM	CHEMBL_ACT_22949982
SCN9A	5.3	IC50	5000	nM	CHEMBL_ACT_22950121
SCN9A	5.28	IC50	5200	nM	CHEMBL_ACT_16910800
KCNH2	5.24	IC50	5700	nM	CHEMBL_ACT_16911220
KCNH2	5.22	IC50	6000	nM	CHEMBL_ACT_22950134
SCN2A	5	IC50	10100	nM	CHEMBL_ACT_16910954
SCN2A	5	IC50	10000	nM	CHEMBL_ACT_22950124

Target pathways

Aggregated over 1 target gene(s): SCN5A.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	1	SCN5A
L1CAM interactions	1	SCN5A
Muscle contraction	1	SCN5A
Axon guidance	1	SCN5A
Interaction between L1 and Ankyrins	1	SCN5A
Cardiac conduction	1	SCN5A
Phase 0 - rapid depolarisation	1	SCN5A
Nervous system development	1	SCN5A

Dominant GO biological processes

GO term	Targets
regulation of heart rate	1
cardiac conduction system development	1
cardiac ventricle development	1
brainstem development	1
sodium ion transport	1
positive regulation of sodium ion transport	1
response to denervation involved in regulation of muscle adaptation	1
telencephalon development	1
cerebellum development	1
sodium ion transmembrane transport	1
odontogenesis of dentin-containing tooth	1
positive regulation of action potential	1
positive regulation of epithelial cell proliferation	1
membrane depolarization	1
cardiac muscle contraction	1

Indications & clinical

Indications

4 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
hypertrophic cardiomyopathy	2	MONDO:0005045	EFO:0000538
myocardial ischemia	2	MONDO:0024644	EFO:1001375

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

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE1	6
PHASE2	2
PHASE2/PHASE3	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02291237	PHASE2/PHASE3	TERMINATED	Effect of Eleclazine (GS-6615) on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy
NCT02300558	PHASE3	TERMINATED	Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3
NCT02104583	PHASE2	COMPLETED	Evaluating Ventricular Arrhythmia in Subjects With Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy-Defibrillator
NCT02377336	PHASE2	WITHDRAWN	GS-6615 in Adults With Chronic Stable Angina and Coronary Artery Disease
NCT01847391	PHASE1	COMPLETED	A Phase 1 Study to Assess the Safety,Tolerability, and Pharmacokinetics of GS-6615 in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365506	PHASE1	COMPLETED	Study to Evaluate the Effect of Eleclazine on QT, Safety, and Tolerability in Participants With Long QT2 Syndrome
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function

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.

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

Molecule	Source	Status	Shared targets
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	SCN5A
AMIODARONE	ChEMBL	Phase 4 (approved)	SCN5A
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	SCN5A
AMLODIPINE	ChEMBL	Phase 4 (approved)	SCN5A
ASENAPINE	ChEMBL	Phase 4 (approved)	SCN5A
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SCN5A
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SCN5A
BENZONATATE	ChEMBL	Phase 4 (approved)	SCN5A
BEPRIDIL	ChEMBL	Phase 4 (approved)	SCN5A
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	SCN5A
CARBAMAZEPINE	ChEMBL	Phase 4 (approved)	SCN5A
CARVEDILOL	ChEMBL	Phase 4 (approved)	SCN5A
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SCN5A
CISAPRIDE	ChEMBL	Phase 4 (approved)	SCN5A
CLEMASTINE	ChEMBL	Phase 4 (approved)	SCN5A
CLOZAPINE	ChEMBL	Phase 4 (approved)	SCN5A
DABIGATRAN ETEXILATE	ChEMBL	Phase 4 (approved)	SCN5A
DARIFENACIN	ChEMBL	Phase 4 (approved)	SCN5A
DARUNAVIR	ChEMBL	Phase 4 (approved)	SCN5A
DASATINIB	ChEMBL	Phase 4 (approved)	SCN5A
DEFERASIROX	ChEMBL	Phase 4 (approved)	SCN5A
DESIPRAMINE	ChEMBL	Phase 4 (approved)	SCN5A
DIBUCAINE	ChEMBL	Phase 4 (approved)	SCN5A
DILTIAZEM	ChEMBL	Phase 4 (approved)	SCN5A
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SCN5A
DOMPERIDONE	ChEMBL	Phase 4 (approved)	SCN5A
DROPERIDOL	ChEMBL	Phase 4 (approved)	SCN5A
DULOXETINE	ChEMBL	Phase 4 (approved)	SCN5A
ETIDOCAINE	ChEMBL	Phase 4 (approved)	SCN5A
FEDRATINIB	ChEMBL	Phase 4 (approved)	SCN5A
FELODIPINE	ChEMBL	Phase 4 (approved)	SCN5A
FLECAINIDE	ChEMBL	Phase 4 (approved)	SCN5A
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	SCN5A
FLUVOXAMINE	ChEMBL	Phase 4 (approved)	SCN5A
HALOPERIDOL	ChEMBL	Phase 4 (approved)	SCN5A
IMIPRAMINE	ChEMBL	Phase 4 (approved)	SCN5A
ISRADIPINE	ChEMBL	Phase 4 (approved)	SCN5A
LAMOTRIGINE	ChEMBL	Phase 4 (approved)	SCN5A
LETERMOVIR	ChEMBL	Phase 4 (approved)	SCN5A
LIDOCAINE	ChEMBL	Phase 4 (approved)	SCN5A
LOPERAMIDE	ChEMBL	Phase 4 (approved)	SCN5A
LOPINAVIR	ChEMBL	Phase 4 (approved)	SCN5A
LURASIDONE	ChEMBL	Phase 4 (approved)	SCN5A
MEXILETINE	ChEMBL	Phase 4 (approved)	SCN5A
MIBEFRADIL	ChEMBL	Phase 4 (approved)	SCN5A
MITOXANTRONE	ChEMBL	Phase 4 (approved)	SCN5A
MOXIFLOXACIN	ChEMBL	Phase 4 (approved)	SCN5A
NEBIVOLOL	ChEMBL	Phase 4 (approved)	SCN5A
NELFINAVIR	ChEMBL	Phase 4 (approved)	SCN5A
NICARDIPINE	ChEMBL	Phase 4 (approved)	SCN5A
NIFEDIPINE	ChEMBL	Phase 4 (approved)	SCN5A
NIMODIPINE	ChEMBL	Phase 4 (approved)	SCN5A
NINTEDANIB	ChEMBL	Phase 4 (approved)	SCN5A
NISOLDIPINE	ChEMBL	Phase 4 (approved)	SCN5A
OLICERIDINE	ChEMBL	Phase 4 (approved)	SCN5A
PALONOSETRON	ChEMBL	Phase 4 (approved)	SCN5A
PAROXETINE	ChEMBL	Phase 4 (approved)	SCN5A
PHENYTOIN	ChEMBL	Phase 4 (approved)	SCN5A
PIMOZIDE	ChEMBL	Phase 4 (approved)	SCN5A
PITOLISANT	ChEMBL	Phase 4 (approved)	SCN5A