Vanoxerine
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Also known as GBR 12909GBR-12909VanoxerinaSID11111021SID11111022SID11113492SID26751714SID90341225SID50104404SID124879806VanoredxineVANOXERINE HYDROCHLORIDEGBR12909
Summary
Vanoxerine (CHEMBL281594) is a phase-3 clinical-stage small-molecule dopamine uptake inhibitor targeting SIGMAR1, TMEM97, and SLC6A3; indicated across 4 conditions including atrial fibrillation and atrial flutter.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 3 (SIGMAR1, TMEM97, SLC6A3)
- Indications: 4 conditions
- Clinical trials: 6
- Chemistry: 450.6 Da · C28H32F2N2O
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL281594 |
| Name | Vanoxerine |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 3455 |
| ChEBI | CHEBI:64089 |
| Molecular formula | C28H32F2N2O |
| Molecular weight | 450.6 |
| InChIKey | NAUWTFJOPJWYOT-UHFFFAOYSA-N |
SMILES: C1CN(CCN1CCCC2=CC=CC=C2)CCOC(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F
IUPAC name: 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine
ChEBI definition: An N-alkylpiperazine that consists of piperazine bearing 2-bis(4-fluorophenyl)methoxy]ethyl and 3-phenylpropyl groups at positions 1 and 4 respectively. Potent, competitive inhibitor of dopamine uptake (Ki = 1 nM for inhibition of striatal dopamine uptake). Has > 100-fold lower affinity for the noradrenalin and 5-HT uptake carriers. Also a potent sigma ligand (IC50 = 48 nM). Centrally active following systemic administration.
Pharmacological roles (ChEBI): dopamine uptake inhibitor.
Also known as: GBR 12909, GBR-12909, Vanoxerina, Vanoxerine, SID11111021, SID11111022, SID11113492, SID26751714, SID90341225, SID50104404, SID124879806, Vanoredxine
Parent form; salt/anhydrous children: CHEMBL153260, CHEMBL543876, CHEMBL542933, CHEMBL1973367
Patent coverage: 334 distinct patent families (1,128 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 |
|---|---|---|---|---|---|
| SIGMAR1 | sigma non-opioid intracellular receptor 1 | Binding | 7.32 | 2.6% | Q99720 |
| TMEM97 | σ2 | Binding | 7.32 | 8% | Q5BJF2 |
| SLC6A3 | DAT | Inhibition | 9 | 0.2% | Q01959 |
Broader ChEMBL bioactivity targets: 38 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Microtubule-associated protein tau, Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Thrombopoietin, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A.
Bioactivity
ChEMBL activities: 148 potent at pChembl ≥ 5 of 194 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P23977 | 10.22 | Ki | 0.06 | nM | CHEMBL_ACT_924015 |
| SLC6A3 | 9.44 | Ki | 0.36 | nM | CHEMBL_ACT_1049725 |
| P23977 | 9.37 | IC50 | 0.43 | nM | CHEMBL_ACT_1616573 |
| SLC6A3 | 9.15 | IC50 | 0.71 | nM | CHEMBL_ACT_18221601 |
| P23977 | 9.06 | Ki | 0.88 | nM | CHEMBL_ACT_1111797 |
| SIGMAR1 | 9 | IC50 | 1 | nM | CHEMBL_ACT_1171142 |
| P23977 | 9 | IC50 | 1 | nM | CHEMBL_ACT_333811 |
| P23977 | 8.76 | IC50 | 1.75 | nM | CHEMBL_ACT_128938 |
| P23977 | 8.75 | Ki | 1.77 | nM | CHEMBL_ACT_2259675 |
| P23977 | 8.64 | IC50 | 2.3 | nM | CHEMBL_ACT_1222532 |
| P23977 | 8.58 | IC50 | 2.63 | nM | CHEMBL_ACT_128939 |
| P23977 | 8.52 | IC50 | 3 | nM | CHEMBL_ACT_333813 |
| P23977 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_1066081 |
| P23977 | 8.43 | IC50 | 3.7 | nM | CHEMBL_ACT_128933 |
| P23977 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_2054284 |
| SLC6A3 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_2210943 |
| P23977 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_377400 |
| P23977 | 8.43 | IC50 | 3.7 | nM | CHEMBL_ACT_404700 |
| SLC6A3 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_484167 |
| P23977 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_609330 |
| P23977 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_656118 |
| P23977 | 8.43 | Ki | 3.7 | nM | CHEMBL_ACT_917803 |
| P23977 | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_333812 |
| P23977 | 8.37 | IC50 | 4.3 | nM | CHEMBL_ACT_1159101 |
| P23977 | 8.37 | Ki | 4.3 | nM | CHEMBL_ACT_377403 |
| SLC6A3 | 8.37 | IC50 | 4.3 | nM | CHEMBL_ACT_484169 |
| P23977 | 8.37 | IC50 | 4.3 | nM | CHEMBL_ACT_811090 |
| P23977 | 8.37 | IC50 | 4.3 | nM | CHEMBL_ACT_820686 |
| SLC6A3 | 8.33 | Ki | 4.7 | nM | CHEMBL_ACT_24507974 |
| SLC6A3 | 8.29 | Ki | 5.07 | nM | CHEMBL_ACT_2701477 |
Target pathways
Aggregated over 3 target gene(s): SIGMAR1, TMEM97, SLC6A3.
Top Reactome pathways
17 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Disease | 2 | SIGMAR1, SLC6A3 |
| Neurotransmitter clearance | 1 | SLC6A3 |
| Transmission across Chemical Synapses | 1 | SLC6A3 |
| Neuronal System | 1 | SLC6A3 |
| Dopamine clearance from the synaptic cleft | 1 | SLC6A3 |
| Transport of small molecules | 1 | SLC6A3 |
| R-HSA-425366 | 1 | SLC6A3 |
| SLC-mediated transmembrane transport | 1 | SLC6A3 |
| SLC-mediated transport of neurotransmitters | 1 | SLC6A3 |
| Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | 1 | SLC6A3 |
| SLC transporter disorders | 1 | SLC6A3 |
| Disorders of transmembrane transporters | 1 | SLC6A3 |
| Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | 1 | SLC6A3 |
| Infectious disease | 1 | SIGMAR1 |
| Potential therapeutics for SARS | 1 | SIGMAR1 |
| SARS-CoV Infections | 1 | SIGMAR1 |
| Viral Infection Pathways | 1 | SIGMAR1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| lipid transport | 1 |
| nervous system development | 1 |
| regulation of neuron apoptotic process | 1 |
| protein homotrimerization | 1 |
| response to alcohol | 1 |
| regulation of postsynapse assembly | 1 |
| G protein-coupled opioid receptor signaling pathway | 1 |
| regulation of cell growth | 1 |
| regulation of intracellular lipid transport | 1 |
| regulation of intracellular cholesterol transport | 1 |
| cholesterol homeostasis | 1 |
| positive regulation of wound healing | 1 |
| positive regulation of lipoprotein transport | 1 |
| neurotransmitter transport | 1 |
| amino acid transport | 1 |
Indications & clinical
Indications
4 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 |
|---|---|---|---|
| atrial fibrillation | 3 | MONDO:0004981 | EFO:0000275 |
| atrial flutter | 2 | MONDO:0005310 | EFO:0003911 |
| cocaine dependence | 1 | MONDO:0005186 | EFO:0002610 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 6.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 4 |
| PHASE3 | 1 |
| PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02454283 | PHASE3 | TERMINATED | Safety and Efficacy of Vanoxerine for the Conversion of Subjects With Recent Onset Atrial Fibrillation or Flutter to Normal Sinus Rhythm |
| NCT01691313 | PHASE2 | COMPLETED | Safety and Efficacy of Vanoxerine for Conversion of Atrial Fibrillation or Flutter to Normal Sinus Rhythm |
| NCT00051896 | PHASE1 | UNKNOWN | Assessment of the Potential Interactions Between Cocaine and GBR 12909 - 1 |
| NCT00089687 | PHASE1 | UNKNOWN | GBR 12909 Study in Cocaine Experienced African American Volunteers - 1 |
| NCT00100113 | PHASE1 | UNKNOWN | Assessment of Potential Interactions Between GBR 12909 and Cocaine - 1 |
| NCT00218049 | PHASE1 | TERMINATED | Interaction Between Vanoxerine (GBR 12909) and Cocaine in Cocaine Dependent Individuals |
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.
573 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| CLEMASTINE | ChEMBL + PubChem | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| Dihydroergotamine | ChEMBL + PubChem | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| HALOPERIDOL | ChEMBL + PubChem | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| CINACALCET | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| LOPERAMIDE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| PITOLISANT | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| TEGASEROD | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| VILAZODONE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3, TMEM97 |
| FANANSERIN | ChEMBL | Phase 2 | SIGMAR1, SLC6A3, TMEM97 |
| NIGULDIPINE | ChEMBL | Phase 2 | SIGMAR1, SLC6A3, TMEM97 |
| RITANSERIN | ChEMBL | Phase 2 | SIGMAR1, SLC6A3, TMEM97 |
| SPIRAMIDE | ChEMBL | Phase 2 | SIGMAR1, SLC6A3, TMEM97 |
| CHLOROQUINE | ChEMBL + PubChem | Phase 4 (approved) | SIGMAR1, TMEM97 |
| HYDROXYCHLOROQUINE | ChEMBL + PubChem | Phase 4 (approved) | SIGMAR1, TMEM97 |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | SIGMAR1, TMEM97 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| BETAXOLOL | ChEMBL | Phase 4 (approved) | SIGMAR1, TMEM97 |
| BROMHEXINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | SLC6A3, TMEM97 |
| CARBETAPENTANE | ChEMBL | Phase 4 (approved) | SIGMAR1, TMEM97 |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | SLC6A3, TMEM97 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| COCAINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| DEXCHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| DIMENHYDRINATE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| DOBUTAMINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| DONEPEZIL | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| ECONAZOLE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| FENTANYL | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| FLUOXETINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| FLUPHENAZINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| FLUVOXAMINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| ILOPERIDONE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| INDACATEROL | ChEMBL | Phase 4 (approved) | SLC6A3, TMEM97 |
| KETANSERIN | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| LABETALOL | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| LASMIDITAN | ChEMBL | Phase 4 (approved) | SIGMAR1, TMEM97 |
| MAZINDOL | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| MEPAZINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| NAFTIFINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| NEFAZODONE | ChEMBL | Phase 4 (approved) | SLC6A3, TMEM97 |
| OXYBUTYNIN | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| PAROXETINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| PENTAZOCINE | ChEMBL | Phase 4 (approved) | SIGMAR1, TMEM97 |
| PERHEXILINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| PINDOLOL | ChEMBL | Phase 4 (approved) | SLC6A3, TMEM97 |
| PRAZOSIN | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| PROCHLORPERAZINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| PROPAFENONE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| PROPRANOLOL | ChEMBL | Phase 4 (approved) | SIGMAR1, TMEM97 |
| PYRILAMINE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
| RALOXIFENE | ChEMBL | Phase 4 (approved) | SIGMAR1, SLC6A3 |
Related Atlas pages
- Genes: SIGMAR1, TMEM97, SLC6A3
- Diseases: atrial fibrillation
- Drugs: Clemastine, Dihydroergotamine, Haloperidol, Astemizole, Azelastine, Brexpiprazole, Cinacalcet, Loperamide, Pitolisant, Tegaserod, Vilazodone, Chloroquine, Hydroxychloroquine, Pramipexole, Amiodarone, Amitriptyline, Benztropine, Betaxolol, Bromhexine, Cannabidiol, Carbetapentane, Cariprazine, Chlorpromazine, Cinnarizine, Citalopram, Clomipramine, Cocaine, Dexchlorpheniramine, Dimenhydrinate, Dobutamine, Donepezil, Econazole, Fentanyl, Fluoxetine, Fluphenazine, Fluvoxamine, Iloperidone, Indacaterol, Ketanserin, Labetalol, Lasmiditan, Mazindol, Mepazine, Naftifine, Nefazodone, Oxybutynin, Paroxetine, Pentazocine, Perhexiline, Pindolol, Prazosin, Prochlorperazine, Propafenone, Propranolol, Pyrilamine, Raloxifene