Levorphanol
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Also known as AromaroneIDS-NL-007LevorfanolLevorphan(-)-levorphanol
Summary
Levorphanol (CHEMBL592) is an approved small molecule targeting OPRM1 and GRIN2C; indicated across 1 condition.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- Targets: 2 (OPRM1, GRIN2C)
- Indications: 1 condition
- Clinical trials: 2
- Chemistry: 257.37 Da · C17H23NO
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL592 |
| Name | Levorphanol |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 5359272 |
| Molecular formula | C17H23NO |
| Molecular weight | 257.37 |
| InChIKey | JAQUASYNZVUNQP-USXIJHARSA-N |
SMILES: CN1CC[C@]23CCCC[C@H]2[C@H]1CC4=C3C=C(C=C4)O
IUPAC name: (1R,9R,10R)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol
Also known as: Aromarone, IDS-NL-007, Levorfanol, Levorphan, Levorphanol, levorphanol, (-)-levorphanol, LEVORPHANOL
Parent form; salt/anhydrous children: CHEMBL1628243, CHEMBL2062261, CHEMBL3249801, CHEMBL3989768
Patent coverage: 26,206 distinct patent families (75,131 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 |
|---|---|---|---|---|---|
| OPRM1 | μ receptor | Agonist | 9.89 | 0% | P35372 |
| GRIN2C | GluN2C | 6.22 | 0.2% | Q14957 |
Broader ChEMBL bioactivity targets: 18 (assay-derived). Sample: Alpha-2A adrenergic receptor, Glutamate NMDA receptor, Glutamate [NMDA] receptor, Sodium channel alpha subunits; brain (Types I, II, III), Sodium-dependent serotonin transporter, Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Mu-type opioid receptor.
Bioactivity
ChEMBL activities: 48 potent at pChembl ≥ 5 of 56 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| OPRM1 | 9.89 | IC50 | 0.13 | nM | CHEMBL_ACT_595646 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_10949101 |
| P97266 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_1143444 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_1668591 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_1896200 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_2227168 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_25611554 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_371818 |
| OPRM1 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_731399 |
| P97266 | 9.68 | Ki | 0.21 | nM | CHEMBL_ACT_909107 |
| P42866 | 9.52 | Ki | 0.3 | nM | CHEMBL_ACT_1157104 |
| P97266 | 9.22 | IC50 | 0.6 | nM | CHEMBL_ACT_1118376 |
| O55242 | 8.72 | Ki | 1.9 | nM | CHEMBL_ACT_1157105 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_10949061 |
| P41144 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_1143446 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_1668593 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_1896201 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_2227170 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_25611540 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_371820 |
| OPRK1 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_731401 |
| P41144 | 8.64 | Ki | 2.3 | nM | CHEMBL_ACT_909109 |
| OPRD1 | 8.54 | IC50 | 2.9 | nM | CHEMBL_ACT_1118377 |
| OPRK1 | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_595645 |
| OPRD1 | 8.38 | Ki | 4.2 | nM | CHEMBL_ACT_10949022 |
| OPRD1 | 8.38 | Ki | 4.2 | nM | CHEMBL_ACT_1143445 |
| OPRD1 | 8.38 | Ki | 4.2 | nM | CHEMBL_ACT_1668592 |
| OPRD1 | 8.38 | Ki | 4.2 | nM | CHEMBL_ACT_1896202 |
| OPRD1 | 8.38 | Ki | 4.2 | nM | CHEMBL_ACT_2227169 |
| OPRD1 | 8.38 | Ki | 4.2 | nM | CHEMBL_ACT_25611600 |
Target pathways
Aggregated over 2 target gene(s): OPRM1, GRIN2C.
Top Reactome pathways
12 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Opioid Signalling | 1 | OPRM1 |
| G-protein activation | 1 | OPRM1 |
| Peptide ligand-binding receptors | 1 | OPRM1 |
| G alpha (i) signalling events | 1 | OPRM1 |
| Unblocking of NMDA receptors, glutamate binding and activation | 1 | GRIN2C |
| Interleukin-4 and Interleukin-13 signaling | 1 | OPRM1 |
| Neurexins and neuroligins | 1 | GRIN2C |
| Synaptic adhesion-like molecules | 1 | GRIN2C |
| MECP2 regulates neuronal receptors and channels | 1 | OPRM1 |
| Assembly and cell surface presentation of NMDA receptors | 1 | GRIN2C |
| Negative regulation of NMDA receptor-mediated neuronal transmission | 1 | GRIN2C |
| Long-term potentiation | 1 | GRIN2C |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| G protein-coupled receptor signaling pathway | 1 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 1 |
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | 1 |
| adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| neuropeptide signaling pathway | 1 |
| sensory perception | 1 |
| negative regulation of cell population proliferation | 1 |
| sensory perception of pain | 1 |
| G protein-coupled opioid receptor signaling pathway | 1 |
| negative regulation of nitric oxide biosynthetic process | 1 |
| behavioral response to ethanol | 1 |
| positive regulation of neurogenesis | 1 |
| negative regulation of cytosolic calcium ion concentration | 1 |
| negative regulation of Wnt protein secretion | 1 |
Indications & clinical
Indications
1 indication (0 at ChEMBL trial phase 4).
The 1 indication record carries no mapped disease name (EFO/MeSH-only); none shown.
Clinical trials
Total trials: 2.
Phase distribution
| Phase | Trials |
|---|---|
| EARLY_PHASE1 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03579446 | EARLY_PHASE1 | TERMINATED | Levorphanol as a Second Line Opioid in Reducing Pain in Patients With Cancer |
| NCT00275249 | Not specified | COMPLETED | Evolution of Analgesic Tolerance With Opioids |
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.
422 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| CHLORPROMAZINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2C, OPRM1 |
| DEXTROMETHORPHAN | ChEMBL + PubChem | Phase 4 (approved) | GRIN2C, OPRM1 |
| KETAMINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2C, OPRM1 |
| ORPHENADRINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2C, OPRM1 |
| ESMETHADONE | ChEMBL | Phase 3 | GRIN2C, OPRM1 |
| BUDIPINE | ChEMBL | Phase 2 | GRIN2C, OPRM1 |
| DEXTRORPHAN | ChEMBL | Phase 2 | GRIN2C, OPRM1 |
| AMANTADINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2C |
| Dihydroergotamine | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| ELUXADOLINE | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| MAVORIXAFOR | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| MEMANTINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2C |
| PIMAVANSERIN | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| PROPOXYPHENE | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| REGORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| VORAPAXAR | ChEMBL + PubChem | Phase 4 (approved) | OPRM1 |
| ALFENTANIL | ChEMBL | Phase 4 (approved) | OPRM1 |
| ALOGLIPTIN | ChEMBL | Phase 4 (approved) | OPRM1 |
| ALPIDEM | ChEMBL | Phase 4 (approved) | OPRM1 |
| ALVIMOPAN | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMBENONIUM | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMILORIDE | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMODIAQUINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | OPRM1 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | OPRM1 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | OPRM1 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BENZIODARONE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BENZYDAMINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | OPRM1 |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | OPRM1 |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | OPRM1 |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | OPRM1 |
| BUPRENORPHINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| BUTORPHANOL | ChEMBL | Phase 4 (approved) | OPRM1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | OPRM1 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | OPRM1 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | OPRM1 |
| CASPOFUNGIN | ChEMBL | Phase 4 (approved) | OPRM1 |
| CETRORELIX | ChEMBL | Phase 4 (approved) | OPRM1 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | OPRM1 |
| CINACALCET | ChEMBL | Phase 4 (approved) | OPRM1 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | OPRM1 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | OPRM1 |
| CLOMIPHENE | ChEMBL | Phase 4 (approved) | OPRM1 |
Related Atlas pages
- Genes: OPRM1, GRIN2C
- Drugs: Chlorpromazine, Dextromethorphan, Ketamine, Orphenadrine, Esmethadone, Amantadine, Dihydroergotamine, Eluxadoline, Mavorixafor, Memantine, Pimavanserin, Propoxyphene, Regorafenib, Vorapaxar, Alfentanil, Alogliptin, Alpidem, Alvimopan, Ambenonium, Amiloride, Amiodarone, Amitriptyline, Amlodipine, Amodiaquine, Amoxapine, Antazoline, Aripiprazole, Astemizole, Atomoxetine, Azelastine, Bazedoxifene, Benfluorex, Benzbromarone, Benziodarone, Benztropine, Benzydamine, Bepridil, Bexarotene, Bithionol, Bosutinib, Bromocriptine, Bromodiphenhydramine, Bromperidol, Buprenorphine, Butorphanol, Candesartan Cilexetil, Cannabidiol, Carvedilol, Caspofungin, Cetrorelix, Chlorhexidine, Chlorprothixene, Cinacalcet, Cinnarizine, Citalopram, Clemastine, Clomiphene