Tetrodotoxin

Summary

Tetrodotoxin (CHEMBL507974) is a phase-3 clinical-stage small molecule targeting SCN1A, SCN2A, and SCN3A.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 9 (SCN1A, SCN2A, SCN3A…)
• Clinical trials: 6
• Chemistry: 319.27 Da · C11H17N3O8

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL507974
Name	Tetrodotoxin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11174599
Molecular formula	C11H17N3O8
Molecular weight	319.27
InChIKey	CFMYXEVWODSLAX-QOZOJKKESA-N

SMILES: C([C@@]1([C@H]2[C@@H]3[C@H](N=C(N[C@@]34[C@@H]([C@@H]1O[C@]([C@H]4O)(O2)O)O)N)O)O)O

IUPAC name: (1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol

Also known as: Araregai toxin, Babylonia japonica toxin 1, Bjt 1, Maculotoxin, Pft-1 toxin, Spheroidine, Tarichatoxin, Tectin, Tetrodotoxin, Tetrodotoxina, Tetrodotoxine, TTX

Patent coverage: 524 distinct patent families (1,034 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,031 (100%) 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
SCN1A	Nav1.1	Pore blocker		0%	P35498
SCN2A	Nav1.2	Pore blocker	8	0.1%	Q99250
SCN3A	Nav1.3	Pore blocker	8.4	0.1%	Q9NY46
SCN4A	Nav1.4	Pore blocker	7.6	0%	P35499
SCN5A	Nav1.5	Pore blocker	5.8	0.2%	Q14524
SCN8A	Nav1.6	Pore blocker	8.2	0.7%	Q9UQD0
SCN9A	Nav1.7	Pore blocker	7.6	0%	Q15858
SCN10A	Nav1.8	Pore blocker	4.2	0.1%	Q9Y5Y9
SCN11A	Nav1.9	Pore blocker	4.4	0%	Q9UI33

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Sodium channel protein type 1 subunit alpha, Sodium channel protein type 8 subunit alpha, Sodium channel protein type 5 subunit alpha, Sodium channel protein type 4 subunit alpha, Sodium channel protein type 11 subunit alpha, Sodium channel protein type 2 subunit alpha, Sodium channel protein type 7 subunit alpha, Sodium channel protein type 5 subunit alpha, Voltage-gated sodium channel, Sodium channel protein type 2 subunit alpha.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 22 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SCN3A	9	IC50	1	nM	CHEMBL_ACT_26139600
F1LQQ7	8.74	Kd	1.8	nM	CHEMBL_ACT_19213824
SCN8A	8.64	IC50	2.3	nM	CHEMBL_ACT_18916080
SCN3A	8.4	IC50	4	nM	CHEMBL_ACT_26139550
P04775	8.4	IC50	4	nM	CHEMBL_ACT_970800
SCN1A	8.39	IC50	4.1	nM	CHEMBL_ACT_18916028
SCN3A	8.28	IC50	5.3	nM	CHEMBL_ACT_18916046
Q9WTU3	8.22	IC50	6	nM	CHEMBL_ACT_16863618
SCN9A	8.22	IC50	6	nM	CHEMBL_ACT_6204919
SCN4A	8.12	IC50	7.6	nM	CHEMBL_ACT_18916055
P04774	8	IC50	10	nM	CHEMBL_ACT_16863613
P04775	8	IC50	10	nM	CHEMBL_ACT_16863614
SCN2A	7.85	IC50	14	nM	CHEMBL_ACT_18916039
P04775	7.85	IC50	14	nM	CHEMBL_ACT_316581
P08104	7.82	IC50	15	nM	CHEMBL_ACT_16863615
SCN4A	7.6	IC50	25	nM	CHEMBL_ACT_16863616
SCN9A	7.6	IC50	25	nM	CHEMBL_ACT_16863619
SCN7A	7.44	IC50	36	nM	CHEMBL_ACT_18916016
O88457	6	IC50	1000	nM	CHEMBL_ACT_16863621
SCN5A	6	IC50	1000	nM	CHEMBL_ACT_18916068
P15389	5.7	IC50	2000	nM	CHEMBL_ACT_16863617
SCN5A	5.39	IC50	4110	nM	CHEMBL_ACT_26115725

Target pathways

Aggregated over 9 target gene(s): SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A, SCN10A, SCN11A.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
L1CAM interactions	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Muscle contraction	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Axon guidance	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Interaction between L1 and Ankyrins	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Cardiac conduction	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Phase 0 - rapid depolarisation	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Nervous system development	9	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Sensory Perception	3	SCN2A, SCN3A, SCN9A
Sensory perception of taste	3	SCN2A, SCN3A, SCN9A
Sensory perception of sweet, bitter, and umami (glutamate) taste	3	SCN2A, SCN3A, SCN9A

Dominant GO biological processes

GO term	Targets
sodium ion transport	9
sodium ion transmembrane transport	9
cardiac muscle cell action potential involved in contraction	9
monoatomic ion transport	9
monoatomic ion transmembrane transport	9
transmembrane transport	9
monoatomic cation transmembrane transport	8
action potential	7
regulation of heart rate	6
membrane depolarization during action potential	5
neuronal action potential	4
regulation of membrane potential	4
cardiac muscle cell action potential	4
regulation of muscle system process	4
behavioral response to pain	3

Indications & clinical

Indications

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE3	2
PHASE2	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00725114	PHASE3	COMPLETED	Safety & Efficacy Study of Subcutaneous Tetrodotoxin for Moderate to Severe Inadequately Controlled Cancer-related Pain
NCT00726011	PHASE3	COMPLETED	Tetrodotoxin Open-label Efficacy and Safety Continuation Study
NCT01655823	PHASE2	TERMINATED	The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From Chemotherapy Treatment
NCT05359133	PHASE2	TERMINATED	A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
NCT01527734	PHASE1	COMPLETED	Comparison Study of Liquid and Lyophilized Formulations of Subcutaneous Tetrodotoxin (TTX) in Healthy Volunteers
NCT04083833	PHASE1	COMPLETED	A Phase 1, Single Ascending Dose, Randomized, Double-Blind, Placebo and Positive Controlled Study to Evaluate the Cardiovascular Effect of Tetrodotoxin in Healthy Adult Subjects

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.

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

Molecule	Source	Status	Shared targets
AMIODARONE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
DILTIAZEM	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
MEXILETINE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
MIBEFRADIL	ChEMBL	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
SERTINDOLE	ChEMBL	Phase 4 (approved)	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
AJMALINE	ChEMBL	Phase 3	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
NITRENDIPINE	ChEMBL	Phase 3	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
TEDISAMIL	ChEMBL	Phase 3	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
CIFENLINE	ChEMBL	Phase 2	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Lamotrigine	ChEMBL + PubChem	Phase 4 (approved)	SCN10A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
ELECLAZINE	ChEMBL	Phase 3	SCN10A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
VIXOTRIGINE	ChEMBL	Phase 3	SCN10A, SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
PF-05089771	ChEMBL	Phase 2	SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A
Dofetilide	PubChem	Approved	SCN10A, SCN11A, SCN1A, SCN2A, SCN3A, SCN4A, SCN8A
Carbamazepine	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN9A
Lidocaine	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN4A, SCN5A, SCN9A
TETRACAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A
PHENYTOIN	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN4A, SCN5A
FUNAPIDE	ChEMBL	Phase 2	SCN10A, SCN2A, SCN5A, SCN8A, SCN9A
DESIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
DIBUCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
DIPHENHYDRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
DROPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
FELODIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
FLUPHENAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
LOPERAMIDE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
NISOLDIPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
QUINIDINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
RILUZOLE	ChEMBL + PubChem	Phase 4 (approved)	SCN2A, SCN4A, SCN5A, SCN9A
THIORIDAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
VERAPAMIL	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
BEPRIDIL	ChEMBL	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
ETIDOCAINE	ChEMBL	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
PRENYLAMINE	ChEMBL	Phase 4 (approved)	SCN1A, SCN2A, SCN3A, SCN5A
DS-1971	ChEMBL	Phase 2	SCN2A, SCN5A, SCN8A, SCN9A
MEPRYLCAINE	ChEMBL	Phase 2	SCN1A, SCN2A, SCN3A, SCN5A
PF-04531083	ChEMBL	Phase 2	SCN10A, SCN1A, SCN5A, SCN9A
BROMPHENIRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
CHLORPHENIRAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
COCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
CYPROHEPTADINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
DICYCLOMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
LEVORPHANOL	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PHENOXYBENZAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PHENTOLAMINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PRAMOXINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PRAZOSIN	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PRILOCAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PROMETHAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
PROPARACAINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
QUININE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
RESERPINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
TETRABENAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A
TRIFLUOPERAZINE	ChEMBL + PubChem	Phase 4 (approved)	SCN1A, SCN2A, SCN3A