Setmelanotide
drugOn this page
Also known as BIM-22493ImcivreeRM-493Setmelanotida
Summary
Setmelanotide (CHEMBL3301624) is an approved protein (ATC A08AA12) targeting MC1R, MC3R, and MC4R; indicated across 5 conditions including obesity disorder and bardet-biedl syndrome.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Protein
- ATC class: A08AA12
- Targets: 4 (MC1R, MC3R, MC4R…)
- Indications: 5 conditions
- Clinical trials: 25
- Chemistry: 1117.3 Da · C49H68N18O9S2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL3301624 |
| Name | Setmelanotide |
| Type | Protein |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 11993702 |
| ATC | A08AA12 |
| Molecular formula | C49H68N18O9S2 |
| Molecular weight | 1117.3 |
| InChIKey | HDHDTKMUACZDAA-PHNIDTBTSA-N |
SMILES: C[C@@H]1C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N)CC2=CNC3=CC=CC=C32)CCCN=C(N)N)CC4=CC=CC=C4)CC5=CN=CN5
IUPAC name: (4R,7S,10S,13R,16S,19R,22R)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-13-benzyl-10-[3-(diaminomethylideneamino)propyl]-16-(1H-imidazol-5-ylmethyl)-7-(1H-indol-3-ylmethyl)-19-methyl-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexazacyclotricosane-4-carboxamide
Also known as: BIM-22493, Imcivree, RM-493, Setmelanotida, Setmelanotide, SETMELANOTIDE, setmelanotide
Parent form; salt/anhydrous children: CHEMBL4650273
Patent coverage: 256 distinct patent families (679 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 550 (81%) 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 |
|---|---|---|---|---|---|
| MC1R | MC1 receptor | Agonist | 8.41 | 1% | Q01726 |
| MC3R | MC3 receptor | Agonist | 8 | 0.1% | P41968 |
| MC4R | MC4 receptor | Agonist | 8.68 | 0% | P32245 |
| MC5R | MC5 receptor | Agonist | 6.37 | 0% | P33032 |
Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Melanocortin receptor 4, Melanocortin receptor 4, Melanocyte-stimulating hormone receptor, Melanocortin receptor 5, Melanocortin receptor 3.
Bioactivity
ChEMBL activities: 22 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 |
|---|---|---|---|---|---|
| MC3R | 9.82 | EC50 | 0.15 | nM | CHEMBL_ACT_24362763 |
| MC3R | 9.82 | EC50 | 0.15 | nM | CHEMBL_ACT_24697728 |
| MC1R | 9.8 | EC50 | 0.16 | nM | CHEMBL_ACT_24362735 |
| MC1R | 9.8 | EC50 | 0.16 | nM | CHEMBL_ACT_24697694 |
| MC4R | 9.57 | EC50 | 0.27 | nM | CHEMBL_ACT_25500524 |
| MC4R | 9.57 | IC50 | 0.27 | nM | CHEMBL_ACT_29222748 |
| P70596 | 9.55 | EC50 | 0.28 | nM | CHEMBL_ACT_25500525 |
| MC4R | 9.41 | EC50 | 0.39 | nM | CHEMBL_ACT_24362791 |
| MC4R | 9.4 | EC50 | 0.4 | nM | CHEMBL_ACT_24697759 |
| MC4R | 8.68 | Ki | 2.1 | nM | CHEMBL_ACT_29222747 |
| MC1R | 8.41 | Ki | 3.9 | nM | CHEMBL_ACT_29222751 |
| MC4R | 8.39 | Ki | 4.07 | nM | CHEMBL_ACT_24362875 |
| MC4R | 8.37 | Ki | 4.27 | nM | CHEMBL_ACT_24697663 |
| MC1R | 8.34 | Ki | 4.57 | nM | CHEMBL_ACT_24362819 |
| MC1R | 8.34 | Ki | 4.57 | nM | CHEMBL_ACT_24697601 |
| MC3R | 8.28 | IC50 | 5.3 | nM | CHEMBL_ACT_29222750 |
| MC1R | 8.24 | IC50 | 5.8 | nM | CHEMBL_ACT_29222752 |
| MC3R | 8 | Ki | 10 | nM | CHEMBL_ACT_29222749 |
| MC3R | 7.88 | Ki | 13.18 | nM | CHEMBL_ACT_24362847 |
| MC3R | 7.88 | Ki | 13.18 | nM | CHEMBL_ACT_24697632 |
| MC5R | 5.73 | IC50 | 1862 | nM | CHEMBL_ACT_24697790 |
| MC5R | 5.72 | IC50 | 1905 | nM | CHEMBL_ACT_24362903 |
Target pathways
Aggregated over 4 target gene(s): MC1R, MC3R, MC4R, MC5R.
Top Reactome pathways
10 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Developmental Biology | 4 | MC1R, MC3R, MC4R, MC5R |
| Signal Transduction | 4 | MC1R, MC3R, MC4R, MC5R |
| Signaling by GPCR | 4 | MC1R, MC3R, MC4R, MC5R |
| Class A/1 (Rhodopsin-like receptors) | 4 | MC1R, MC3R, MC4R, MC5R |
| Peptide ligand-binding receptors | 4 | MC1R, MC3R, MC4R, MC5R |
| GPCR downstream signalling | 4 | MC1R, MC3R, MC4R, MC5R |
| G alpha (s) signalling events | 4 | MC1R, MC3R, MC4R, MC5R |
| GPCR ligand binding | 4 | MC1R, MC3R, MC4R, MC5R |
| MITF-M-regulated melanocyte development | 4 | MC1R, MC3R, MC4R, MC5R |
| Transcriptional and post-translational regulation of MITF-M expression and activity | 4 | MC1R, MC3R, MC4R, MC5R |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | 4 |
| signal transduction | 4 |
| G protein-coupled receptor signaling pathway | 4 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 3 |
| regulation of feeding behavior | 3 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 2 |
| adenylate cyclase-modulating G protein-coupled receptor signaling pathway | 2 |
| UV protection | 1 |
| sensory perception of pain | 1 |
| negative regulation of tumor necrosis factor production | 1 |
| intracellular signal transduction | 1 |
| melanin biosynthetic process | 1 |
| pigmentation | 1 |
| positive regulation of transcription by RNA polymerase II | 1 |
| positive regulation of melanin biosynthetic process | 1 |
Indications & clinical
Indications
5 indications (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 |
|---|---|---|---|
| obesity disorder | 4 | MONDO:0011122 | EFO:0001073 |
| Bardet-Biedl syndrome | 3 | MONDO:0015229 | MONDO:0015229 |
| Prader-Willi syndrome | 2 | MONDO:0008300 | MONDO:0008300 |
| morbid obesity | 1 | MONDO:0005139 | EFO:0001074 |
| kidney failure | 1 | MONDO:0001106 | HP:0000083 |
Clinical trials
Total trials: 25.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE3 | 9 |
| PHASE2 | 9 |
| PHASE1 | 3 |
| PHASE4 | 1 |
| PHASE2/PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05046132 | PHASE4 | COMPLETED | Study of Setmelanotide Effects on QTc (Corrected QT) Interval in Healthy Participants |
| NCT05093634 | PHASE3 | ACTIVE_NOT_RECRUITING | EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway |
| NCT05774756 | PHASE3 | ACTIVE_NOT_RECRUITING | A Trial of Setmelanotide in Acquired Hypothalamic Obesity |
| NCT06596135 | PHASE3 | ENROLLING_BY_INVITATION | Open-Label Extension Study of Setmelanotide |
| NCT06760546 | PHASE3 | RECRUITING | A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756) |
| NCT02896192 | PHASE3 | COMPLETED | Setmelanotide for the Treatment of Early-Onset Pro-Opiomelanocortin (POMC) Deficiency Obesity |
| NCT03287960 | PHASE3 | COMPLETED | Setmelanotide for the Treatment of Leptin Receptor (LEPR) Deficiency Obesity |
| NCT03651765 | PHASE2/PHASE3 | COMPLETED | Long Term Extension Trial of Setmelanotide |
| NCT03746522 | PHASE3 | COMPLETED | Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity |
| NCT04966741 | PHASE3 | COMPLETED | Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity |
| NCT05194124 | PHASE3 | COMPLETED | Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway |
| NCT06772597 | PHASE2 | ACTIVE_NOT_RECRUITING | A Study of Setmelanotide in Patients With Prader-Willi Syndrome |
| NCT07496463 | PHASE2 | NOT_YET_RECRUITING | Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a) |
| NCT01749137 | PHASE2 | COMPLETED | Phase 2 Study to Evaluate Safety and Efficacy of RM-493 in Obese Participants |
| NCT02041195 | PHASE1/PHASE2 | COMPLETED | Phase 1b/2a Study to Evaluate Safety and Efficacy of Setmelanotide in Obese Patients |
| NCT02311673 | PHASE2 | COMPLETED | Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome |
| NCT02507492 | PHASE2 | UNKNOWN | RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients |
| NCT03013543 | PHASE2 | COMPLETED | Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity |
| NCT03262610 | PHASE2 | COMPLETED | Setmelanotide in a Single Patient With Partial Lipodystrophy |
| NCT04725240 | PHASE2 | COMPLETED | Open-Label Study of Setmelanotide in Hypothalamic Obesity |
| NCT04963231 | PHASE2 | COMPLETED | DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway |
| NCT01867437 | PHASE1 | COMPLETED | Effects of RM-493 on Energy Expenditure in Obese Individuals |
| NCT02431442 | PHASE1 | COMPLETED | Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RM-493 Administered to Healthy, Obese, Non-diabetic Volunteers |
| NCT04348175 | PHASE1 | COMPLETED | A Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment |
| NCT05183802 | Not specified | APPROVED_FOR_MARKETING | An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS) |
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.
173 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| AFAMELANOTIDE | ChEMBL + PubChem | Phase 4 (approved) | MC1R, MC3R, MC4R, MC5R |
| BREMELANOTIDE | ChEMBL | Phase 4 (approved) | MC1R, MC3R, MC4R, MC5R |
| INTERMEDINE | ChEMBL | Phase 2 | MC1R, MC3R, MC4R, MC5R |
| AMIODARONE | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| COLISTIN | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| FLUPHENAZINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| MICONAZOLE | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| SERTRALINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| TAMOXIFEN | ChEMBL | Phase 4 (approved) | MC3R, MC4R, MC5R |
| CLOZAPINE | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| Ivacaftor | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| Linagliptin | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| PIMOZIDE | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| PYRAZINAMIDE | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| TEGASEROD | ChEMBL + PubChem | Phase 4 (approved) | MC3R, MC4R |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| DULOXETINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| ECONAZOLE | ChEMBL | Phase 4 (approved) | MC3R, MC5R |
| FENOTEROL | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| FLUSPIRILENE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| GRAMICIDIN | ChEMBL | Phase 4 (approved) | MC4R, MC5R |
| HALOPERIDOL | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| IMIPRAMINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| LIDOCAINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| MEFLOQUINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| MITOXANTRONE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| MODAFINIL | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| NAFARELIN | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| PROCHLORPERAZINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| PROMETHAZINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| RIFAXIMIN | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| RIMONABANT | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| ROSIGLITAZONE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| TERFENADINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| THIORIDAZINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| TRIFLUOPERAZINE | ChEMBL | Phase 4 (approved) | MC3R, MC4R |
| PL-8177 | ChEMBL | Phase 2 | MC1R, MC4R |
| Abiraterone | PubChem | Approved | MC3R, MC4R |
| Aclidinium Bromide | PubChem | Approved | MC3R, MC4R |
| Acyclovir | PubChem | Approved | MC3R, MC4R |
| Allopurinol | PubChem | Approved | MC3R, MC4R |
| Alogliptin | PubChem | Approved | MC3R, MC4R |
| Amiloride | PubChem | Approved | MC3R, MC4R |
| Anagrelide | PubChem | Approved | MC3R, MC4R |
| Aprepitant | PubChem | Approved | MC3R, MC4R |
| Atazanavir | PubChem | Approved | MC3R, MC4R |
| Betamethasone Valerate | PubChem | Approved | MC3R, MC4R |
| Bosentan | PubChem | Approved | MC3R, MC4R |
Related Atlas pages
- Genes: MC1R, MC3R, MC4R, MC5R
- Diseases: obesity disorder, Bardet-Biedl syndrome
- Drugs: Afamelanotide, Bremelanotide, Amiodarone, Astemizole, Chlorpromazine, Colistin, Fluphenazine, Miconazole, Sertraline, Tamoxifen, Clozapine, Crizotinib, Desloratadine, Ivacaftor, Linagliptin, Pimozide, Pyrazinamide, Tegaserod, Amitriptyline, Amlodipine, Antazoline, Bepridil, Bosutinib, Carvedilol, Chlorhexidine, Clemastine, Clomipramine, Duloxetine, Econazole, Fenoterol, Fluspirilene, Gramicidin, Haloperidol, Imipramine, Lidocaine, Mefloquine, Mitoxantrone, Modafinil, Nafarelin, Prochlorperazine, Promethazine, Rifaximin, Rimonabant, Rosiglitazone, Terfenadine, Thioridazine, Trifluoperazine, Abiraterone, Aclidinium Bromide, Acyclovir, Allopurinol, Alogliptin, Amiloride, Anagrelide, Aprepitant, Atazanavir, Betamethasone Valerate, Bosentan