Lofepramine
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Also known as LofepraminaSID50111779SID50111780C0164746
Summary
Lofepramine (CHEMBL87708) is an approved small-molecule antidepressant (ATC N06AA07) targeting SLC6A2 and SLC6A4; indicated across 1 condition including depressive disorder.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N06AA07
- Targets: 2 (SLC6A2, SLC6A4)
- Indications: 1 condition
- Chemistry: 419 Da · C26H27ClN2O
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL87708 |
| Name | Lofepramine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 3947 |
| ChEBI | CHEBI:47782 |
| ATC | N06AA07 |
| Molecular formula | C26H27ClN2O |
| Molecular weight | 419 |
| InChIKey | SAPNXPWPAUFAJU-UHFFFAOYSA-N |
SMILES: CN(CCCN1C2=CC=CC=C2CCC3=CC=CC=C31)CC(=O)C4=CC=C(C=C4)Cl
IUPAC name: 1-(4-chlorophenyl)-2-[3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl-methylamino]ethanone
Pharmacological roles (ChEBI): antidepressant.
Also known as: Lofepramina, Lofepramine, SID50111779, SID50111780, LOFEPRAMINE, lofepramine, C0164746
Parent form; salt/anhydrous children: CHEMBL2106638
Patent coverage: 1,967 distinct patent families (8,170 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 8,131 (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 |
|---|---|---|---|---|---|
| SLC6A2 | NET | Inhibition | 8.27 | 0.4% | P23975 |
| SLC6A4 | SERT | Inhibition | 7.22 | 0.7% | P31645 |
Broader ChEMBL bioactivity targets: 28 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, 4’-phosphopantetheinyl transferase ffp, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Beta-2 adrenergic receptor, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, Cannabinoid receptor 1, Sodium-dependent noradrenaline transporter, 5-hydroxytryptamine receptor 2A.
Bioactivity
ChEMBL activities: 18 potent at pChembl ≥ 5 of 32 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| SLC6A2 | 7.66 | AC50 | 22 | nM | CHEMBL_ACT_25144549 |
| SLC6A4 | 7.41 | AC50 | 39 | nM | CHEMBL_ACT_25149886 |
| HRH1 | 6.19 | AC50 | 650 | nM | CHEMBL_ACT_25212044 |
| NR1I2 | 5.92 | AC50 | 1200 | nM | CHEMBL_ACT_25224131 |
| Q63921 | 5.89 | AC50 | 1300 | nM | CHEMBL_ACT_25173940 |
| P22002 | 5.62 | AC50 | 2400 | nM | CHEMBL_ACT_25119238 |
| HTR2C | 5.57 | AC50 | 2700 | nM | CHEMBL_ACT_25131354 |
| DRD3 | 5.52 | AC50 | 3000 | nM | CHEMBL_ACT_25193072 |
| NR1I2 | 5.5 | AC50 | 3200 | nM | CHEMBL_ACT_25187862 |
| KCNH2 | 5.48 | AC50 | 3300 | nM | CHEMBL_ACT_25117163 |
| CNR1 | 5.46 | AC50 | 3500 | nM | CHEMBL_ACT_25230437 |
| ADRA2B | 5.4 | AC50 | 4000 | nM | CHEMBL_ACT_25143246 |
| CHRM1 | 5.37 | AC50 | 4300 | nM | CHEMBL_ACT_25134983 |
| ADRA1A | 5.36 | AC50 | 4400 | nM | CHEMBL_ACT_25217754 |
| CHRM3 | 5.33 | AC50 | 4700 | nM | CHEMBL_ACT_25136248 |
| OPRK1 | 5.32 | AC50 | 4800 | nM | CHEMBL_ACT_25129013 |
| HTR2A | 5.18 | AC50 | 6600 | nM | CHEMBL_ACT_25224749 |
| CNR1 | 5.16 | AC50 | 6900 | nM | CHEMBL_ACT_25181357 |
Target pathways
Aggregated over 2 target gene(s): SLC6A2, SLC6A4.
Top Reactome pathways
12 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| SLC-mediated transport of neurotransmitters | 2 | SLC6A2, SLC6A4 |
| Neurotransmitter clearance | 1 | SLC6A4 |
| Transmission across Chemical Synapses | 1 | SLC6A4 |
| Neuronal System | 1 | SLC6A4 |
| Disease | 1 | SLC6A2 |
| Serotonin clearance from the synaptic cleft | 1 | SLC6A4 |
| Transport of small molecules | 1 | SLC6A2 |
| R-HSA-425366 | 1 | SLC6A2 |
| SLC-mediated transmembrane transport | 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 | 2 |
| amino acid transport | 2 |
| response to xenobiotic stimulus | 2 |
| obsolete monoamine transport | 2 |
| sodium ion transmembrane transport | 2 |
| transmembrane transport | 2 |
| neurotransmitter reuptake | 2 |
| chemical synaptic transmission | 1 |
| obsolete norepinephrine transport | 1 |
| response to pain | 1 |
| dopamine uptake involved in synaptic transmission | 1 |
| norepinephrine uptake | 1 |
| neuron cellular homeostasis | 1 |
| catecholamine uptake | 1 |
| chloride transmembrane transport | 1 |
Indications & clinical
Indications
1 indication (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 |
|---|---|---|---|
| depressive disorder | 4 | MONDO:0002050 | MONDO:0002009 |
Clinical trials
Total trials: 0.
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.
592 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| AMITRIPTYLINE | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| Olodaterol | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| PIMAVANSERIN | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| REGORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| Tadalafil | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| TAFENOQUINE | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| UMECLIDINIUM | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| VORAPAXAR | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AMBENONIUM | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ASENAPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ATRACURIUM | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENZPHETAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENZYDAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMHEXINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BUPROPION | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BUTENAFINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CALCIPOTRIENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CALCITRIOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CARBINOXAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CELECOXIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CETIRIZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPHENTERMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CINACALCET | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOMIPHENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOZAPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| COBIMETINIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| COCAINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CYCLOBENZAPRINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| DANAZOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
Related Atlas pages
- Genes: SLC6A2, SLC6A4
- Diseases: depressive disorder
- Drugs: Amitriptyline, Crizotinib, Olodaterol, Pimavanserin, Regorafenib, Tadalafil, Tafenoquine, Umeclidinium, Vorapaxar, Acetophenazine, Alectinib, Ambenonium, Amiodarone, Amoxapine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Atracurium, Azelastine, Bazedoxifene, Benfluorex, Benzphetamine, Benztropine, Benzydamine, Bepridil, Bosutinib, Brexpiprazole, Bromhexine, Bromodiphenhydramine, Bromperidol, Brompheniramine, Bupropion, Butenafine, Cabergoline, Calcipotriene, Calcitriol, Carbinoxamine, Carvedilol, Celecoxib, Cetirizine, Chlorhexidine, Chlorpheniramine, Chlorphentermine, Chlorpromazine, Chlorprothixene, Cinacalcet, Cinnarizine, Citalopram, Clemastine, Clomiphene, Clomipramine, Clotrimazole, Clozapine, Cobimetinib, Cocaine, Cyclobenzaprine, Cyproheptadine, Danazol