Riluzole

Summary

Riluzole (CHEMBL744) is an approved small molecule (ATC N07XX02) targeting KCNN1, KCNN2, and KCNN3; indicated across 25 conditions including amyotrophic lateral sclerosis and multiple system atrophy.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N07XX02
• Targets: 10 (KCNN1, KCNN2, KCNN3…)
• Indications: 25 conditions
• Clinical trials: 73
• Chemistry: 234.2 Da · C8H5F3N2OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL744
Name	Riluzole
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5070
ATC	N07XX02
Molecular formula	C8H5F3N2OS
Molecular weight	234.2
InChIKey	FTALBRSUTCGOEG-UHFFFAOYSA-N

SMILES: C1=CC2=C(C=C1OC(F)(F)F)SC(=N2)N

IUPAC name: 6-(trifluoromethoxy)-1,3-benzothiazol-2-amine

Also known as: BHV-0223, Exservan, NSC-753433, NSC-759823, Rilutek, Riluzol, Riluzole, Riluzole zentiva, RP 54274, RP-54274, Teglutik, Tiglutik

Parent form; salt/anhydrous children: CHEMBL1531817

Patent coverage: 5,001 distinct patent families (20,055 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 19,902 (99%) 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
KCNN1	KCa2.1	Agonist	4.68	1.5%	Q92952
KCNN2	KCa2.2	Agonist	4.89	0%	Q9H2S1
KCNN3	KCa2.3	Agonist	4.9	0%	Q9UGI6
KCNN4	KCa3.1		5.7	0.2%	O15554
TRPC5	TRPC5	Activation	5.04	0%	Q9UL62
KCNK2	K2P2.1			0.2%	O95069
KCNK4	K2P4.1			5.5%	Q9NYG8
KCND2	Kv4.2		3.89	0.3%	Q9NZV8
KCND3	Kv4.3		3.9	5.5%	Q9UK17
KCNH2	Kv11.1	Inhibition	4.3	0.3%	Q12809

Broader ChEMBL bioactivity targets: 30 (assay-derived). Sample: Pyruvate kinase PKM, Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, RecQ-like DNA helicase BLM, NPC intracellular cholesterol transporter 1, Geminin, Ras-related protein Rab-9A, Peripheral myelin protein 22.

Bioactivity

ChEMBL activities: 17 potent at pChembl ≥ 5 of 52 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP1A2	6.5	AC50	316.2	nM	CHEMBL_ACT_6063775
CYP1A2	6.2	AC50	631	nM	CHEMBL_ACT_6068335
SLC6A2	5.76	IC50	1733	nM	CHEMBL_ACT_7826044
SLC6A2	5.76	Ki	1718	nM	CHEMBL_ACT_7826045
SCN2A	5.66	IC50	2200	nM	CHEMBL_ACT_142780
SLC6A2	5.59	AC50	2590	nM	CHEMBL_ACT_25146011
P51450	5.55	Potency	2818	nM	CHEMBL_ACT_4958931
CYP2C9	5.4	Potency	3981	nM	CHEMBL_ACT_5069415
Q01782	5.4	Ki	4000	nM	CHEMBL_ACT_5141241
P04775	5.33	IC50	4730	nM	CHEMBL_ACT_121229
USP2	5.3	Potency	5012	nM	CHEMBL_ACT_4699655
GAA	5.25	Potency	5623	nM	CHEMBL_ACT_4973303
GAA	5.25	Potency	5623	nM	CHEMBL_ACT_5017763
LMNA	5.15	Potency	7080	nM	CHEMBL_ACT_3645950
P51450	5.1	Potency	7943	nM	CHEMBL_ACT_4109504
E9Q401	5	EC50	9900	nM	CHEMBL_ACT_26196579
LMNA	5	Potency	10000	nM	CHEMBL_ACT_3665595

Target pathways

Aggregated over 10 target gene(s): KCNN1, KCNN2, KCNN3, KCNN4, TRPC5, KCNK2, KCNK4, KCND2, KCND3, KCNH2.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	9	KCND2, KCND3, KCNH2, KCNK2, KCNK4, KCNN1, KCNN2, KCNN3, KCNN4
Potassium Channels	9	KCND2, KCND3, KCNH2, KCNK2, KCNK4, KCNN1, KCNN2, KCNN3, KCNN4
Muscle contraction	5	KCND2, KCND3, KCNH2, KCNK2, KCNK4
Cardiac conduction	5	KCND2, KCND3, KCNH2, KCNK2, KCNK4
Ca2+ activated K+ channels	4	KCNN1, KCNN2, KCNN3, KCNN4
Voltage gated Potassium channels	3	KCND2, KCND3, KCNH2
Tandem pore domain potassium channels	2	KCNK2, KCNK4
TWIK related potassium channel (TREK)	2	KCNK2, KCNK4
Phase 4 - resting membrane potential	2	KCNK2, KCNK4
Phase 1 - inactivation of fast Na+ channels	2	KCND2, KCND3
TRP channels	1	TRPC5
Role of second messengers in netrin-1 signaling	1	TRPC5
Phase 3 - rapid repolarisation	1	KCNH2
Sensory processing of sound	1	KCNN2
Sensory processing of sound by outer hair cells of the cochlea	1	KCNN2
Acetylcholine inhibits contraction of outer hair cells	1	KCNN2
Sensory Perception	1	KCNN2

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	10
monoatomic ion transmembrane transport	10
potassium ion transport	9
potassium ion transmembrane transport	9
monoatomic cation transmembrane transport	4
transmembrane transport	4
chemical synaptic transmission	3
neuronal action potential	3
membrane repolarization	3
regulation of potassium ion transmembrane transport	2
calcium ion transport	2
positive regulation of potassium ion transmembrane transport	2
memory	2
detection of mechanical stimulus involved in sensory perception of touch	2
cellular response to hypoxia	2

Indications & clinical

Indications

25 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
amyotrophic lateral sclerosis	4	MONDO:0004976	MONDO:0004976
multiple system atrophy	3	MONDO:0007803	EFO:1001050
spinal cord disorder	3	MONDO:0002545	HP:0002196
Huntington disease	3	MONDO:0007739	MONDO:0007739
progressive supranuclear palsy	3	MONDO:0019037	MONDO:0019037
autism spectrum disorder	2	MONDO:0005258	EFO:0003756
cutaneous melanoma	2	MONDO:0005012	EFO:0000389
obsessive-compulsive disorder	2	MONDO:0008114	EFO:0004242
peripheral neuropathy	2	MONDO:0005244	EFO:0003100
secondary progressive multiple sclerosis	2	MONDO:0000450	EFO:0008522
spinal muscular atrophy	2	MONDO:0001516	EFO:0008525
cerebellar ataxia	2	MONDO:0000437	MONDO:0000437
major depressive disorder	2	MONDO:0002009	MONDO:0002009
depressive disorder	2	MONDO:0002050	MONDO:0002050
atrial fibrillation	2	MONDO:0004981	EFO:0000275
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
multiple sclerosis	2	MONDO:0005301	MONDO:0005301
bipolar disorder	2	MONDO:0004985	MONDO:0004985
spinal cord injury	2	MONDO:0043797	MONDO:0043797
post-traumatic stress disorder	1	MONDO:0005146	EFO:0001358
breast neoplasm	1	MONDO:0021100	MONDO:0007254
neoplasm	1	MONDO:0005070	EFO:0000616

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

Clinical trials

Total trials: 73.

Phase distribution

Phase	Trials
PHASE2	25
PHASE1	11
PHASE2/PHASE3	10
PHASE3	8
PHASE4	6
Not specified	6
EARLY_PHASE1	4
PHASE1/PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00283309	PHASE4	TERMINATED	Memantine or Riluzole Prophylaxis for Corticosteroid-induced Mood and Declarative Memory Changes
NCT00419003	PHASE4	COMPLETED	Research Study for Major Depressive Disorder: Investigation of Glutamate Medications
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00895752	PHASE4	COMPLETED	Riluzole in Fragile X Syndrome
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT02796755	PHASE4	COMPLETED	Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03660917	PHASE2/PHASE3	RECRUITING	Riluzole in Patients With Spinocerebellar Ataxia Type 7
NCT07174492	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients
NCT00211224	PHASE3	TERMINATED	Neuroprotection and Natural History in Parkinson’s Plus Syndromes (NNIPPS)
NCT00277602	PHASE3	COMPLETED	Riluzole in Huntington’s Disease
NCT00353665	PHASE2/PHASE3	COMPLETED	Memantine for Disability in Amyotrophic Lateral Sclerosis (MEDALS)
NCT00774423	PHASE2/PHASE3	COMPLETED	Study to Evaluate the Efficacy of Riluzole in Children and Young Adults With Spinal Muscular Atrophy (SMA)
NCT00818389	PHASE2/PHASE3	TERMINATED	Study to Investigate the Safety and Efficacy of Lithium in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT01104649	PHASE2/PHASE3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT01257828	PHASE3	COMPLETED	Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-Protect)
NCT01597518	PHASE2/PHASE3	TERMINATED	Riluzole in Spinal Cord Injury Study
NCT02588677	PHASE2/PHASE3	COMPLETED	Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)
NCT03017508	PHASE2/PHASE3	COMPLETED	Acute Anxiolytic Effects of Riluzole on Subjects With Social Anxiety Disorder
NCT03272802	PHASE2/PHASE3	UNKNOWN	Treatment Effect of Edaravone in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03347344	PHASE3	COMPLETED	Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)
NCT04745299	PHASE3	COMPLETED	Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS
NCT04950933	PHASE2/PHASE3	UNKNOWN	The Treatment of Amyotrophic Lateral Sclerosis With Huollingshengji Granules
NCT05292209	PHASE2	RECRUITING	RiLuzole to Reduce Atrial FIb Study Using Holter Monitoring
NCT06580002	PHASE2	RECRUITING	Repurposing Riluzole for Cancer-Related Cognitive Impairment: A Pilot Trial
NCT07142291	PHASE2	RECRUITING	PHENOGENE-1A (Cromolyn) Treatment in Patients With Mild to Moderate ALS
NCT07414212	PHASE1/PHASE2	RECRUITING	Evaluation of the Combined Therapy of EH-301 and N-acetylcysteine Together With Riluzole in Amyotrophic Lateral Sclerosis (ALS)
NCT07447050	PHASE2	RECRUITING	Riluzole For Preventing Cognitive Dysfunction in Ca Pts Receiving Chemo (REFOCUS): Pilot Trial
NCT00026052	PHASE2	COMPLETED	Riluzole to Treat Major Depression
NCT00054704	PHASE2	TERMINATED	Riluzole to Treat Depression in Bipolar Disorder
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00251303	PHASE2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00376220	PHASE2	COMPLETED	A Double-Blind Placebo Controlled Trial of Riluzole in Bipolar Depression
NCT00501943	PHASE2	COMPLETED	Neuroprotection With Riluzole Patients With Early Multiple Sclerosis
NCT00523718	PHASE2	COMPLETED	Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder
NCT00805493	PHASE2	TERMINATED	Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder
NCT00866840	PHASE2	COMPLETED	Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
NCT01204918	PHASE2	COMPLETED	Efficacy and Tolerability of Riluzole in Treatment Resistant Depression
NCT01486849	PHASE2	COMPLETED	Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
PROPAFENONE	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2, KCNK2
AMLODIPINE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
CLOTRIMAZOLE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNN4
DARIFENACIN	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
DARUNAVIR	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
Dofetilide	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
DULOXETINE	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
Etravirine	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
FLUOXETINE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
glyburide	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
Lapatinib	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
MEXILETINE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
Moxifloxacin	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
NEBIVOLOL	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
Nelfinavir	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
Nilotinib	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
Palonosetron	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
Quinine	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, KCNK2
Rosiglitazone	ChEMBL + PubChem	Phase 4 (approved)	KCNH2, TRPC5
Sildenafil	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
Silodosin	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
SOLIFENACIN	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
SUNITINIB	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
TOLTERODINE	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
VARDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	KCND3, KCNH2
BEPRIDIL	ChEMBL	Phase 4 (approved)	KCNH2, KCNK2
VERNAKALANT	ChEMBL	Phase 4 (approved)	KCND2, KCNH2
FLUPENTIXOL	ChEMBL	Phase 3	KCNH2, KCNK2
CEPHARANTHINE	ChEMBL	Phase 2	KCNN2, KCNN3
Tadalafil	PubChem	Approved	KCND3, KCNH2
Tubocurarine	PubChem	Approved	KCNN2, KCNN3
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
CARVEDILOL	ChEMBL + PubChem	Phase 4 (approved)	KCNK2
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	KCNK2
DEFERASIROX	ChEMBL + PubChem	Phase 4 (approved)	KCND3
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
FLUPHENAZINE	ChEMBL + PubChem	Phase 4 (approved)	KCNK2
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
LOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	KCNK2
MAVORIXAFOR	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
RELUGOLIX	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
RIOCIGUAT	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	KCNH2
ABEMACICLIB	ChEMBL	Phase 4 (approved)	KCNH2
ACENOCOUMAROL	ChEMBL	Phase 4 (approved)	KCNH2
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	KCNH2
ACLIDINIUM BROMIDE	ChEMBL	Phase 4 (approved)	KCNH2
ALBENDAZOLE	ChEMBL	Phase 4 (approved)	KCNH2
ALMOTRIPTAN	ChEMBL	Phase 4 (approved)	KCNH2
ALOSETRON	ChEMBL	Phase 4 (approved)	KCNH2
ALPIDEM	ChEMBL	Phase 4 (approved)	KCNH2
AMBENONIUM	ChEMBL	Phase 4 (approved)	KCNH2
AMCINONIDE	ChEMBL	Phase 4 (approved)	KCNH2
AMIODARONE	ChEMBL	Phase 4 (approved)	KCNH2