Samidorphan
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Also known as ALKS 33Alks-33RDC-0313SamidorfanoSAMIDORPHAN COMPONENT OF ALKS-5461
Summary
Samidorphan (CHEMBL426084) is an approved small molecule targeting OPRD1, OPRK1, and OPRM1; indicated across 4 conditions including eating disorder and alcohol abuse.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- Targets: 3 (OPRD1, OPRK1, OPRM1)
- Indications: 4 conditions
- Clinical trials: 5
- Chemistry: 370.4 Da · C21H26N2O4
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL426084 |
| Name | Samidorphan |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 11667832 |
| Molecular formula | C21H26N2O4 |
| Molecular weight | 370.4 |
| InChIKey | RYIDHLJADOKWFM-MAODMQOUSA-N |
SMILES: C1CC1CN2CC[C@]34CC(=O)CC[C@]3([C@H]2CC5=C4C(=C(C=C5)C(=O)N)O)O
IUPAC name: (1R,9R,10S)-17-(cyclopropylmethyl)-3,10-dihydroxy-13-oxo-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4-carboxamide
Also known as: ALKS 33, Alks-33, ALKS-33, RDC-0313, Samidorfano, Samidorphan, SAMIDORPHAN COMPONENT OF ALKS-5461, SAMIDORPHAN
Parent form; salt/anhydrous children: CHEMBL471243, CHEMBL2105749
Patent coverage: 140 distinct patent families (373 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 288 (77%) 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 |
|---|---|---|---|---|---|
| OPRD1 | δ receptor | Antagonist | 8.59 | 0.2% | P41143 |
| OPRK1 | κ receptor | Antagonist | 9.64 | 0% | P41145 |
| OPRM1 | μ receptor | Antagonist | 10.28 | 0% | P35372 |
Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor.
Bioactivity
ChEMBL activities: 3 potent at pChembl ≥ 5 of 3 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| OPRM1 | 10.28 | Ki | 0.05 | nM | CHEMBL_ACT_1519226 |
| OPRK1 | 9.64 | Ki | 0.23 | nM | CHEMBL_ACT_1519228 |
| OPRD1 | 8.59 | Ki | 2.6 | nM | CHEMBL_ACT_1519227 |
Target pathways
Aggregated over 3 target gene(s): OPRD1, OPRK1, OPRM1.
Top Reactome pathways
6 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Peptide ligand-binding receptors | 3 | OPRD1, OPRK1, OPRM1 |
| G alpha (i) signalling events | 3 | OPRD1, OPRK1, OPRM1 |
| Interleukin-4 and Interleukin-13 signaling | 2 | OPRD1, OPRM1 |
| MECP2 regulates neuronal receptors and channels | 2 | OPRK1, OPRM1 |
| Opioid Signalling | 1 | OPRM1 |
| G-protein activation | 1 | OPRM1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| G protein-coupled receptor signaling pathway | 3 |
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | 3 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 3 |
| neuropeptide signaling pathway | 3 |
| G protein-coupled opioid receptor signaling pathway | 3 |
| signal transduction | 3 |
| immune response | 2 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 2 |
| response to nicotine | 2 |
| eating behavior | 2 |
| response to ethanol | 2 |
| sensory perception | 2 |
| sensory perception of pain | 2 |
| adult locomotory behavior | 1 |
| negative regulation of gene expression | 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 |
|---|---|---|---|
| eating disorder | 2 | MONDO:0005451 | EFO:0005203 |
| alcohol abuse | 2 | MONDO:0002046 | MONDO:0007079 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 5.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 4 |
| PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02161718 | PHASE2 | COMPLETED | A Study of ALKS 3831 in Subjects With Schizophrenia and Alcohol Use Disorder |
| NCT00800319 | PHASE1 | COMPLETED | ALK33-001: A Study of RDC-0313 Administered to Healthy Adults |
| NCT01046539 | PHASE1 | COMPLETED | Phase 1 Study to Evaluate RDC-0313 Coadministered With Buprenorphine to Opioid-Experienced Healthy Adults |
| NCT01366001 | PHASE1 | COMPLETED | ALK33BUP-101: Safety and Pharmacodynamic Effects of ALKS 33-BUP Administered Alone and When Co-administered With Cocaine |
| NCT02218021 | PHASE1 | COMPLETED | A Study of the Abuse Liability Potential of Samidorphan in Healthy, Non-Dependent, Recreational Opioid Users |
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.
612 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| Dihydroergotamine | ChEMBL + PubChem | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| PROPOXYPHENE | ChEMBL + PubChem | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| TAFAMIDIS | ChEMBL + PubChem | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| ALVIMOPAN | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| BUPRENORPHINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| BUTORPHANOL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| CODEINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| ECONAZOLE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| FENTANYL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| FLUPHENAZINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| FLUSPIRILENE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| HYDROCODONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| HYDROMORPHONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| LANSOPRAZOLE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| LEVORPHANOL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| LOPERAMIDE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| LOXAPINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| MEPERIDINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| METHADONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| METHYLNALTREXONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| MICONAZOLE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| MORPHINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NAFTOPIDIL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NALBUPHINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NALFURAFINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NALMEFENE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NALOXONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NALTREXONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| NELFINAVIR | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| OLICERIDINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| OXYCODONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| OXYMORPHONE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| PAROXETINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| PASIREOTIDE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| PENTAZOCINE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| PIMOZIDE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| RALOXIFENE | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| RITONAVIR | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| SAQUINAVIR | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| SUNITINIB | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| TAMOXIFEN | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| TRAMADOL | ChEMBL | Phase 4 (approved) | OPRD1, OPRK1, OPRM1 |
| ASIMADOLINE | ChEMBL | Phase 3 | OPRD1, OPRK1, OPRM1 |
| ATICAPRANT | ChEMBL | Phase 3 | OPRD1, OPRK1, OPRM1 |
| CEBRANOPADOL | ChEMBL | Phase 3 | OPRD1, OPRK1, OPRM1 |
| NAVACAPRANT | ChEMBL | Phase 3 | OPRD1, OPRK1, OPRM1 |
| TRIMEBUTINE | ChEMBL | Phase 3 | OPRD1, OPRK1, OPRM1 |
| BREMAZOCINE | ChEMBL | Phase 2 | OPRD1, OPRK1, OPRM1 |
| CARFENTANIL | ChEMBL | Phase 2 | OPRD1, OPRK1, OPRM1 |
Related Atlas pages
- Genes: OPRD1, OPRK1, OPRM1
- Drugs: Dihydroergotamine, Propoxyphene, Tafamidis, Alvimopan, Amiodarone, Amlodipine, Amoxapine, Astemizole, Benztropine, Buprenorphine, Butorphanol, Candesartan Cilexetil, Cannabidiol, Chlorpromazine, Cinnarizine, Clotrimazole, Codeine, Diethylstilbestrol, Econazole, Fentanyl, Fluphenazine, Fluspirilene, Hydrocodone, Hydromorphone, Lansoprazole, Levorphanol, Loperamide, Loxapine, Meperidine, Methadone, Methylnaltrexone, Miconazole, Morphine, Naftopidil, Nalbuphine, Nalfurafine, Nalmefene, Naloxone, Naltrexone, Nelfinavir, Oliceridine, Oxycodone, Oxymorphone, Paroxetine, Pasireotide, Pentazocine, Pimozide, Raloxifene, Ritonavir, Saquinavir, Sunitinib, Tamoxifen, Tramadol, Asimadoline, Aticaprant, Cebranopadol, Navacaprant, Trimebutine