Esreboxetine
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Also known as (S,S)-RBX(s,s)-reboxetineEsreboxetinaREBOXETINESs-reboxetineSs-rbxSID11114256
Summary
Esreboxetine (CHEMBL180101) is a phase-3 clinical-stage small molecule targeting SLC6A2; indicated across 4 conditions including fibromyalgia and diabetic neuropathy.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (SLC6A2)
- Indications: 4 conditions
- Clinical trials: 20
- Chemistry: 313.4 Da · C19H23NO3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL180101 |
| Name | Esreboxetine |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 65856 |
| Molecular formula | C19H23NO3 |
| Molecular weight | 313.4 |
| InChIKey | CBQGYUDMJHNJBX-OALUTQOASA-N |
SMILES: CCOC1=CC=CC=C1O[C@H]([C@@H]2CNCCO2)C3=CC=CC=C3
IUPAC name: (2S)-2-[(S)-(2-ethoxyphenoxy)-phenylmethyl]morpholine
Also known as: (S,S)-RBX, (s,s)-reboxetine, Esreboxetina, Esreboxetine, REBOXETINE, S, s-reboxetine, Ss-rbx, (S,S)-reboxetine, SID11114256, ESREBOXETINE, esreboxetine
Parent form; salt/anhydrous children: CHEMBL2103809
Patent coverage: 3,397 distinct patent families (13,337 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 12,834 (96%) 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 |
|---|---|---|---|---|---|
| SLC6A2 | NET | Inhibition | 8 | 0.4% | P23975 |
Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Lysine-specific demethylase 4E, Menin/Histone-lysine N-methyltransferase MLL, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter, Sodium-dependent dopamine transporter, Cytochrome P450 2D6, Sodium-dependent serotonin transporter, Cytochrome P450 2C9, Cytochrome P450 3A4, Aldehyde dehydrogenase 1A1.
Bioactivity
ChEMBL activities: 13 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 |
|---|---|---|---|---|---|
| SLC6A2 | 9.52 | Ki | 0.3 | nM | CHEMBL_ACT_3066012 |
| SLC6A2 | 8.98 | Ki | 1.04 | nM | CHEMBL_ACT_2246861 |
| SLC6A2 | 8.7 | IC50 | 2 | nM | CHEMBL_ACT_12668748 |
| SLC6A2 | 8.52 | IC50 | 3 | nM | CHEMBL_ACT_2243440 |
| SLC6A2 | 8.51 | IC50 | 3.1 | nM | CHEMBL_ACT_2699894 |
| MAPK1 | 7.6 | Potency | 25.1 | nM | CHEMBL_ACT_4524784 |
| SLC6A4 | 6.18 | Ki | 661 | nM | CHEMBL_ACT_2246855 |
| SLC6A4 | 5.5 | IC50 | 3162 | nM | CHEMBL_ACT_12668697 |
| CYP2D6 | 5.5 | IC50 | 3162 | nM | CHEMBL_ACT_12713142 |
| P31652 | 5.28 | IC50 | 5200 | nM | CHEMBL_ACT_2463982 |
| CYP3A4 | 5 | Potency | 10000 | nM | CHEMBL_ACT_4997681 |
| CYP3A4 | 5 | Potency | 10000 | nM | CHEMBL_ACT_5062691 |
| CYP3A4 | 5 | AC50 | 10000 | nM | CHEMBL_ACT_6065779 |
Target pathways
Aggregated over 1 target gene(s): SLC6A2.
Top Reactome pathways
8 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Disease | 1 | SLC6A2 |
| Transport of small molecules | 1 | SLC6A2 |
| R-HSA-425366 | 1 | SLC6A2 |
| SLC-mediated transmembrane transport | 1 | SLC6A2 |
| SLC-mediated transport of neurotransmitters | 1 | SLC6A2 |
| SLC transporter disorders | 1 | SLC6A2 |
| Defective SLC6A2 causes orthostatic intolerance (OI) | 1 | SLC6A2 |
| Disorders of transmembrane transporters | 1 | SLC6A2 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| neurotransmitter transport | 1 |
| amino acid transport | 1 |
| chemical synaptic transmission | 1 |
| response to xenobiotic stimulus | 1 |
| obsolete monoamine transport | 1 |
| obsolete norepinephrine transport | 1 |
| sodium ion transmembrane transport | 1 |
| response to pain | 1 |
| dopamine uptake involved in synaptic transmission | 1 |
| norepinephrine uptake | 1 |
| neuron cellular homeostasis | 1 |
| transmembrane transport | 1 |
| catecholamine uptake | 1 |
| neurotransmitter reuptake | 1 |
| chloride transmembrane 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 |
|---|---|---|---|
| fibromyalgia | 3 | MONDO:0005546 | EFO:0005687 |
| diabetic neuropathy | 2 | MONDO:0006626 | EFO:1000783 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 20.
Phase distribution
| Phase | Trials |
|---|---|
| Not specified | 5 |
| PHASE4 | 4 |
| PHASE3 | 4 |
| PHASE2 | 4 |
| PHASE1 | 3 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00209807 | PHASE4 | UNKNOWN | Effect of Escitalopram vs. Reboxetine on Gastro-intestinal Sensitivity of Patients With Major Depressive Disorder |
| NCT00426946 | PHASE4 | UNKNOWN | Reboxetine Treatment in Depressed Children and Adolescents an 8-Week, Open Study |
| NCT00853866 | PHASE4 | COMPLETED | Enhancement of Motor Function with Reboxetine and Transcranial Direct Current Stimulation |
| NCT01300364 | PHASE4 | UNKNOWN | Reboxetine and Citalopram as an Adjunct Treatment to Second Generation Antipsychotics in the Treatment of Negative Symptoms of Schizophrenia |
| NCT05880342 | PHASE3 | RECRUITING | The Role of the Brain in Mental and Physical Fatigue |
| NCT00796601 | PHASE3 | WITHDRAWN | Maintenance of Efficacy. |
| NCT02179268 | PHASE3 | COMPLETED | Antidepressants and Bone Mineral Density |
| NCT02374567 | PHASE3 | TERMINATED | Pharmacovigilance in Gerontopsychiatric Patients |
| NCT05133804 | PHASE2 | RECRUITING | Efficacy of Reboxetine and Methylphenidate Treatment on Attentional, Sensory and Emotional Dysregulation in Adults With PTSD |
| NCT00138749 | PHASE2 | COMPLETED | An 8 Week Study Looking At The Efficacy, Toleration And Safety Of SS-RBX For Stress Urinary Incontinence. |
| NCT00141128 | PHASE2 | COMPLETED | Evaluation Of A Novel Methodology In The Assessment Of Urethral Function Using SS-RBX. |
| NCT00752505 | PHASE2 | COMPLETED | A Study To Assess Esreboxetine’s Effect On Concentration, Memory, Decision Making And Problem Solving In Patients With Fibromyalgia. |
| NCT00809289 | PHASE1 | COMPLETED | Phase 1 Thorough QT (TQT) Study in Young Healthy Volunteers |
| NCT00886886 | PHASE1 | COMPLETED | Interaction Between Reboxetine and 3,4-Methylenedioxymethamphetamine: Pharmacodynamics (PD) and Pharmacokinetics (PK) |
| NCT04097288 | PHASE1 | COMPLETED | Effects of Single Dose Citalopram and Reboxetine on Urethral and Anal Closure Function on Healthy Female Subjects |
| NCT00421369 | Not specified | COMPLETED | Augmentation of the Antidepressant Action of Sertraline With Triiodothyronine (T3)and Reboxetine: Clinical Efficacy, Adverse Effects and Predictors of Response. |
| NCT00993876 | Not specified | COMPLETED | Cognitive Flexibility in Major Depression in the Course of Pharmacological and Psychotherapeutic Treatment |
| NCT03957174 | Not specified | COMPLETED | Noradrenaline, Acetylcholine and Dynamic Learning in Healthy Humans |
| NCT04371146 | Not specified | COMPLETED | The Role of Dopaminergic and Noradrenergic Neurotransmission in Value- and Salience-based Decision-Making |
| NCT04384562 | Not specified | COMPLETED | Studying the Role of Brain Molecules for Decision Making |
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.
486 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| AMITRIPTYLINE | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| DACOMITINIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| PIMAVANSERIN | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| REGORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| TAFENOQUINE | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| UMECLIDINIUM | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| VORAPAXAR | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ALFACALCIDOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ALFUZOSIN | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMBENONIUM | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMINOCAPROIC ACID | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMODIAQUINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AMPHETAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ASENAPINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| ATRACURIUM | ChEMBL | Phase 4 (approved) | SLC6A2 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENOXINATE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENZIODARONE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENZPHETAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENZYDAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BENZYL BENZOATE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BROMHEXINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BUPROPION | ChEMBL | Phase 4 (approved) | SLC6A2 |
| BUTENAFINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CALCIPOTRIENE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CALCITRIOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CARBINOXAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CASPOFUNGIN | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CELECOXIB | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CETIRIZINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CHLOROXINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
| CHLORPHENTERMINE | ChEMBL | Phase 4 (approved) | SLC6A2 |
Related Atlas pages
- Genes: SLC6A2
- Diseases: fibromyalgia
- Drugs: Amitriptyline, Crizotinib, Dacomitinib, Pimavanserin, Regorafenib, Tafenoquine, Umeclidinium, Vorapaxar, Acetophenazine, Alectinib, Alfacalcidol, Alfuzosin, Ambenonium, Aminocaproic Acid, Amiodarone, Amlodipine, Amodiaquine, Amoxapine, Amphetamine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Atracurium, Azelastine, Bazedoxifene, Benfluorex, Benoxinate, Benperidol, Benziodarone, Benzphetamine, Benztropine, Benzydamine, Benzyl Benzoate, Bepridil, Bexarotene, Bithionol, Bosutinib, Brexpiprazole, Bromhexine, Bromodiphenhydramine, Bromperidol, Brompheniramine, Bupropion, Butenafine, Cabergoline, Calcipotriene, Calcitriol, Candesartan Cilexetil, Cannabidiol, Carbinoxamine, Carvedilol, Caspofungin, Celecoxib, Cetirizine, Chlorhexidine, Chloroxine, Chlorpheniramine, Chlorphentermine