Encenicline

Summary

Encenicline (CHEMBL2151572) is a phase-3 clinical-stage small molecule targeting CHRNA7; indicated across 8 conditions including dementia and alzheimer disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (CHRNA7)
• Indications: 8 conditions
• Clinical trials: 17
• Chemistry: 320.8 Da · C16H17ClN2OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2151572
Name	Encenicline
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	46196517
Molecular formula	C16H17ClN2OS
Molecular weight	320.8
InChIKey	SSRDSYXGYPJKRR-ZDUSSCGKSA-N

SMILES: C1CN2CCC1[C@H](C2)NC(=O)C3=CC4=C(S3)C(=CC=C4)Cl

IUPAC name: N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-chloro-1-benzothiophene-2-carboxamide

Also known as: Enceniclina, Encenicline, Evp-6124, EVP-6124, MT-4666, MT4666, ENCENICLINE, EVP-6124_ENCENICLINE, Encenicline hydrochloride

Parent form; salt/anhydrous children: CHEMBL3137323

Patent coverage: 29 distinct patent families (116 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
CHRNA7	nicotinic acetylcholine receptor α7 subunit	Partial agonist	8.37	0.1%	P36544

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: 5-hydroxytryptamine receptor 3A, Neuronal acetylcholine receptor subunit alpha-7.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
CHRNA7	8.37	Ki	4.3	nM	CHEMBL_ACT_12053410
CHRNA7	8	Ki	9.98	nM	CHEMBL_ACT_12160918
CHRNA7	6.6	EC50	250	nM	CHEMBL_ACT_19278521
HTR3A	6.52	IC50	299	nM	CHEMBL_ACT_12053420
CHRNA7	6.47	EC50	340	nM	CHEMBL_ACT_16529679
CHRNA7	6.41	EC50	390	nM	CHEMBL_ACT_19161410

Target pathways

Aggregated over 1 target gene(s): CHRNA7.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter receptors and postsynaptic signal transmission	1	CHRNA7
Transmission across Chemical Synapses	1	CHRNA7
Neuronal System	1	CHRNA7
Acetylcholine binding and downstream events	1	CHRNA7
Postsynaptic nicotinic acetylcholine receptors	1	CHRNA7
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	CHRNA7

Dominant GO biological processes

GO term	Targets
response to hypoxia	1
monoatomic ion transport	1
calcium ion transport	1
intracellular calcium ion homeostasis	1
signal transduction	1
chemical synaptic transmission	1
learning or memory	1
memory	1
short-term memory	1
positive regulation of cell population proliferation	1
negative regulation of tumor necrosis factor production	1
monoatomic ion transmembrane transport	1
response to nicotine	1
regulation of membrane potential	1
negative regulation of canonical NF-kappaB signal transduction	1

Indications & clinical

Indications

8 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
dementia	3	MONDO:0001627	HP:0000726
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
liver disorder	1	MONDO:0005154	EFO:0001421
schizoaffective disorder	1	MONDO:0005487	EFO:0005411
kidney disorder	1	MONDO:0005240	EFO:0003086
central nervous system disorder	1	MONDO:0002602	EFO:0009386

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

Clinical trials

Total trials: 17.

Phase distribution

Phase	Trials
PHASE3	7
PHASE2	5
PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01714661	PHASE3	COMPLETED	Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy
NCT01714713	PHASE3	COMPLETED	A 26-Week Extension Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy
NCT01716975	PHASE3	COMPLETED	Study of EVP-6124 (Alpha-7 nAChR) as an Adjunctive Pro-Cognitive Treatment in Schizophrenia Subjects on Chronic Stable Atypical Antipsychotic Therapy
NCT01969123	PHASE3	TERMINATED	Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer’s Disease
NCT01969136	PHASE3	TERMINATED	Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer’s Disease
NCT02004392	PHASE3	TERMINATED	Study of the Safety and Clinical Effects of 2 Doses of EVP-6124 in Subjects With Alzheimer’s Disease Who Complete Study EVP-6124-024 or EVP-6124-025
NCT02327182	PHASE3	TERMINATED	Safety Study of MT-4666 in Subjects With Alzheimer’s Disease
NCT00968851	PHASE2	COMPLETED	Safety and Cognitive Function Study of EVP-6124 in Patients With Schizophrenia
NCT01073228	PHASE2	COMPLETED	Safety and Cognitive Function Study of EVP-6124 in Patients With Mild to Moderate Alzheimer’s Disease
NCT01480232	PHASE2	TERMINATED	A Safety and Cognitive Function Study of EVP-6124 Versus Placebo in Subjects With Nicotine Dependence
NCT01764243	PHASE2	COMPLETED	Safety and Efficacy of MT-4666
NCT02246075	PHASE2	WITHDRAWN	Study of the Safety of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer’s Disease Currently Receiving Memantine
NCT00766363	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer’s Disease
NCT01487135	PHASE1	COMPLETED	Phase 1 Study to Assess the Effects of EVP-6124 on the QT/QTc Interval in Healthy Subjects
NCT01556763	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
NCT01984723	PHASE1	COMPLETED	EVP-6124 Renal Impairment Study
NCT01984736	PHASE1	COMPLETED	EVP-6124 Hepatic Impairment Study

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.

27 molecules share ≥1 primary target. Top 27 by shared-target count:

Molecule	Source	Status	Shared targets
ACETYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRNA7
BUPROPION	ChEMBL	Phase 4 (approved)	CHRNA7
CARBAMOYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRNA7
MECAMYLAMINE	ChEMBL	Phase 4 (approved)	CHRNA7
NALTREXONE	ChEMBL	Phase 4 (approved)	CHRNA7
NICOTINE	ChEMBL	Phase 4 (approved)	CHRNA7
TROPISETRON	ChEMBL	Phase 4 (approved)	CHRNA7
VARENICLINE	ChEMBL	Phase 4 (approved)	CHRNA7
CYTISINICLINE	ChEMBL + PubChem	Phase 3 (approved)	CHRNA7
DEXMECAMYLAMINE	ChEMBL	Phase 3	CHRNA7
AZD0328	ChEMBL	Phase 2	CHRNA7
AZD1446	ChEMBL	Phase 2	CHRNA7
BRADANICLINE	ChEMBL	Phase 2	CHRNA7
FACINICLINE	ChEMBL	Phase 2	CHRNA7
GTS-21	ChEMBL	Phase 2	CHRNA7
LEVOMENOL	ChEMBL	Phase 2	CHRNA7
LOBELINE	ChEMBL	Phase 2	CHRNA7
RIVANICLINE	ChEMBL	Phase 2	CHRNA7
SSR180711	ChEMBL	Phase 2	CHRNA7
STILONIUM	ChEMBL	Phase 2	CHRNA7
STILONIUM IODIDE	ChEMBL	Phase 2	CHRNA7
TEBANICLINE	ChEMBL	Phase 2	CHRNA7
TILORONE	ChEMBL	Phase 2	CHRNA7
.gamma.-aminobutyric acid	PubChem	Approved	CHRNA7
Cinacalcet	PubChem	Approved	CHRNA7
Mavorixafor	PubChem	Approved	CHRNA7
Sulindac	PubChem	Approved	CHRNA7