Flupirtine

Summary

Flupirtine (CHEMBL255044) is an approved small molecule (ATC N02BG07) targeting KCNQ2; indicated across 3 conditions including relapsing-remitting multiple sclerosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02BG07
• Targets: 1 (KCNQ2)
• Indications: 3 conditions
• Clinical trials: 18
• Chemistry: 304.32 Da · C15H17FN4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL255044
Name	Flupirtine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	53276
ATC	N02BG07
Molecular formula	C15H17FN4O2
Molecular weight	304.32
InChIKey	JUUFBMODXQKSTD-UHFFFAOYSA-N

SMILES: CCOC(=O)NC1=C(N=C(C=C1)NCC2=CC=C(C=C2)F)N

IUPAC name: ethyl N-[2-amino-6-[(4-fluorophenyl)methylamino]-3-pyridinyl]carbamate

Also known as: Flupirtina, Flupirtine, Flupirtinte, W-2964, SID11111201, SID90341043, SID124880149, FLUPIRTINE, SID174006272, Retigabine, Flupirtine (Maleate), flupirtine

Parent form; salt/anhydrous children: CHEMBL543869, CHEMBL1256752

Patent coverage: 1,670 distinct patent families (5,706 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 5,590 (98%) 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		5	0%	O43526

Broader ChEMBL bioactivity targets: 23 (assay-derived). Sample: Alpha-2A adrenergic receptor, Estrogen receptor, Thromboxane A2 receptor, 5-hydroxytryptamine receptor 1A, Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3), Prostaglandin G/H synthase 2, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Adenosine receptor A3, Cytochrome P450 2D6.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 34 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NFKB1	7.55	Potency	28.2	nM	CHEMBL_ACT_3671975
NFKB1	7.55	Potency	28.2	nM	CHEMBL_ACT_4585257
KCNQ3	6.25	EC50	560	nM	CHEMBL_ACT_19051145
SHMT2	6.03	IC50	933.2	nM	CHEMBL_ACT_19333076
KCNQ3	5.72	EC50	1900	nM	CHEMBL_ACT_29127336
PTGS2	5.64	AC50	2300	nM	CHEMBL_ACT_25166605
ESR1	5.52	AC50	3000	nM	CHEMBL_ACT_25167677
HIF1A	5.4	Potency	3981	nM	CHEMBL_ACT_4117580
HIF1A	5.4	Potency	3981	nM	CHEMBL_ACT_4519631
CYP3A4	5.1	Potency	7943	nM	CHEMBL_ACT_4961370
CYP3A4	5.1	Potency	7943	nM	CHEMBL_ACT_5026859
CYP3A4	5.1	AC50	7943	nM	CHEMBL_ACT_6036517
CASP7	5	Potency	10000	nM	CHEMBL_ACT_3802548

Target pathways

Aggregated over 1 target gene(s): KCNQ2.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	1	KCNQ2
Developmental Biology	1	KCNQ2
Potassium Channels	1	KCNQ2
Voltage gated Potassium channels	1	KCNQ2
L1CAM interactions	1	KCNQ2
Axon guidance	1	KCNQ2
Interaction between L1 and Ankyrins	1	KCNQ2
Nervous system development	1	KCNQ2

Dominant GO biological processes

GO term	Targets
action potential	1
chemical synaptic transmission	1
nervous system development	1
potassium ion transmembrane transport	1
monoatomic ion transport	1
potassium ion transport	1
monoatomic ion transmembrane transport	1
transmembrane transport	1

Indications & clinical

Indications

3 indications (2 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
relapsing-remitting multiple sclerosis	2	MONDO:0005314	EFO:0003929

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

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE1	6
PHASE3	5
PHASE2	3
Not specified	2
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01607346	PHASE4	TERMINATED	An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures
NCT00232596	PHASE3	COMPLETED	Retigabine (Adjunctive Therapy) Efficacy and Safety Study for Partial Onset Refractory Seizures in Epilepsy
NCT00235755	PHASE3	COMPLETED	Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy
NCT01648101	PHASE3	TERMINATED	Assessment of the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures
NCT01668654	PHASE3	TERMINATED	Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects (>= 12 Years Old) With POS or LGS
NCT01823159	PHASE3	COMPLETED	Cortical Excitability Changes Induced by Retigabine: a Transcranial Magnetic Stimulation Study
NCT00612105	PHASE2	COMPLETED	Safety/Efficacy Study of Retigabine vs. Placebo in Post-Herpetic Neuralgia (PHN)
NCT00623415	PHASE2	TERMINATED	Flupirtine as Oral Treatment in Multiple Sclerosis
NCT01494584	PHASE2	TERMINATED	Study in Pediatric Subjects With Epilepsy
NCT01450865	PHASE1	COMPLETED	Effect of the Kv7-channel Opener Flupirtine on the Excitability of Human Peripheral Myelinated Axons in Vivo
NCT01462669	PHASE1	COMPLETED	Crossover Study to Evaluate the Pharmacokinetics of Ezogabine/Retigabine in Taiwanese Subjects
NCT01480609	PHASE1	COMPLETED	Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and Its N-acetyl Metabolite
NCT01583036	PHASE1	COMPLETED	An Open-label, Single-centre Study Evaluating the Pharmacokinetics of Digoxin Alone and When Administered at Various Doses of Ezogabine/Retigabine in Healthy Adults. The Pharmacokinetics of Ezogabine/Retigabine and the N-acetyl Metabolite of Ezogabine/Retigabine (NAMR) Will Also be Assessed
NCT01676246	PHASE1	COMPLETED	Pharmacokinetics, Metabolism and Analgesic Effects of Flupirtine
NCT01691872	PHASE1	WITHDRAWN	Pharmacokinetic Study of Retigabine Extended Release (XR) Formulation in Healthy Adult Japanese and Caucasian Subjects
NCT06971250	EARLY_PHASE1	COMPLETED	Peripheral KV7 Activation for Pain Relief
NCT01457989	Not specified	COMPLETED	Meta-Analysis Plan for Pooled Data for Studies VRX-RET-E22-303 and VRX-RET-E22-304
NCT01587339	Not specified	COMPLETED	Systematic Review: Retigabine for Adjunctive Therapy in Partial Epilepsy

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 2 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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
AZETUKALNER	ChEMBL	Phase 3	KCNQ2
FLINDOKALNER	ChEMBL	Phase 3	KCNQ2
Quinidine	PubChem	Approved	KCNQ2