Azetukalner

Summary

Azetukalner (CHEMBL5095264) is a phase-3 clinical-stage small molecule targeting KCNQ2 and KCNQ3; indicated across 5 conditions including visual epilepsy and epilepsy with generalized tonic-clonic seizures.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (KCNQ2, KCNQ3)
• Indications: 5 conditions
• Clinical trials: 12
• Chemistry: 368.5 Da · C23H29FN2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5095264
Name	Azetukalner
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	24743936
Molecular formula	C23H29FN2O
Molecular weight	368.5
InChIKey	FJNPZKZPWVVSON-UHFFFAOYSA-N

SMILES: CC1=CC(=CC(=C1NC(=O)CC(C)(C)C)C)N2CCC3=C(C2)C=CC(=C3)F

IUPAC name: N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide

Also known as: Azetukalner, Encukalner, XEN-1101, XEN1101, AZETUKALNER

Patent coverage: 40 distinct patent families (115 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 75 (65%) 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
KCNQ2	Kv7.2	Activation		0%	O43526
KCNQ3	Kv7.3	Activation		0.1%	O43525

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Potassium voltage-gated channel subfamily KQT member 2.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
KCNQ2	7.01	EC50	98	nM	CHEMBL_ACT_28721174

Target pathways

Aggregated over 2 target gene(s): KCNQ2, KCNQ3.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNQ2, KCNQ3
Developmental Biology	2	KCNQ2, KCNQ3
Potassium Channels	2	KCNQ2, KCNQ3
Voltage gated Potassium channels	2	KCNQ2, KCNQ3
L1CAM interactions	2	KCNQ2, KCNQ3
Axon guidance	2	KCNQ2, KCNQ3
Interaction between L1 and Ankyrins	2	KCNQ2, KCNQ3
Nervous system development	2	KCNQ2, KCNQ3

Dominant GO biological processes

GO term	Targets
chemical synaptic transmission	2
potassium ion transmembrane transport	2
monoatomic ion transport	2
potassium ion transport	2
monoatomic ion transmembrane transport	2
transmembrane transport	2
action potential	1
nervous system development	1
protein targeting	1
protein import into nucleus	1
exocytosis	1
endocytosis	1
sensory perception of sound	1
gene expression	1
response to auditory stimulus	1

Indications & clinical

Indications

5 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
visual epilepsy	3	MONDO:0001386	HP:0001250
epilepsy with generalized tonic-clonic seizures	3	MONDO:0005754	HP:0002069
major depressive disorder	2	MONDO:0002009	MONDO:0002009
focal epilepsy	2	MONDO:0005384	EFO:0004263

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

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE3	9
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05667142	PHASE3	RECRUITING	A Study to Evaluate XEN1101 as Adjunctive Therapy in Primary Generalized Tonic-Clonic Seizures
NCT05716100	PHASE3	RECRUITING	A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)
NCT05718817	PHASE3	ENROLLING_BY_INVITATION	An Open-label Study of XEN1101 in Epilepsy
NCT06775379	PHASE3	RECRUITING	A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder
NCT06922110	PHASE3	ENROLLING_BY_INVITATION	An Open-Label Study of Azetukalner in Major Depressive Disorder
NCT07076407	PHASE3	RECRUITING	A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)
NCT07172516	PHASE3	RECRUITING	A Randomized Study of Azetukalner Versus Placebo in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression)
NCT07217860	PHASE3	ENROLLING_BY_INVITATION	An Open-label Study of Azetukalner in Bipolar I or II Depression (X-CEED-OLE)
NCT05614063	PHASE3	COMPLETED	A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures
NCT03796962	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy
NCT04827901	PHASE2	COMPLETED	XEN1101 for Major Depressive Disorder
NCT05376150	PHASE2	COMPLETED	A Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 in Major Depressive Disorder

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.

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

Molecule	Source	Status	Shared targets
EZOGABINE	ChEMBL	Phase 4 (approved)	KCNQ2, KCNQ3
FLUPIRTINE	ChEMBL	Phase 4 (approved)	KCNQ2, KCNQ3
FLINDOKALNER	ChEMBL	Phase 3	KCNQ2, KCNQ3
Quinidine	PubChem	Approved	KCNQ2