Afamelanotide
drugOn this page
Also known as (nle4,d-phe7)-.alpha.-mshAfamelanotidaCUV-1647CUV1647MelanotanMelanotan iMelanotan-1Ndp-alpha-mshScenesseNDP-MSH[Nle4D-Phe7]R-MSHAc-SYS-Nle-EH-DPhe-RWGKPV-NH2NA
Summary
Afamelanotide (CHEMBL441738) is an approved protein dermatologic drug (ATC D02BB02) targeting MC1R, MC3R, and MC4R; indicated across 7 conditions including erythropoietic protoporphyria and vitiligo.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Protein
- ATC class: D02BB02
- Targets: 4 (MC1R, MC3R, MC4R…)
- Indications: 7 conditions
- Clinical trials: 21
- Chemistry: C78H111N21O19
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL441738 |
| Name | Afamelanotide |
| Type | Protein |
| Max phase | 4 |
| ChEBI | CHEBI:136034 |
| ATC | D02BB02 |
| Molecular formula | C78H111N21O19 |
| InChIKey | UAHFGYDRQSXQEB-LEBBXHLNSA-N |
SMILES: CCCC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1cncn1)C(=O)N[C@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc2ccccc12)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(N)=O)C(C)C
ChEBI definition: A polypeptide comprising of 13 amino acids which is an analogue of α-melanocyte stimulating hormone. It is approved as a dermatologic drug for the prevention of phototoxicity in adult patients with erythropoietic protoporphyria.
Pharmacological roles (ChEBI): dermatologic drug.
Also known as: (nle4,d-phe7)-.alpha.-msh, Afamelanotida, Afamelanotide, CUV-1647, CUV1647, Melanotan, Melanotan i, Melanotan-1, Ndp-alpha-msh, Scenesse, NDP-alpha-MSH, NDP-MSH
Parent form; salt/anhydrous children: CHEMBL4297213
Patent coverage: 266 distinct patent families (602 SureChEMBL compound mentions), from 4 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 |
|---|---|---|---|---|---|
| MC1R | MC1 receptor | Full agonist | 10 | 1% | Q01726 |
| MC3R | MC3 receptor | Full agonist | 8.9 | 0.1% | P41968 |
| MC4R | MC4 receptor | Full agonist | 8.8 | 0% | P32245 |
| MC5R | MC5 receptor | Full agonist | 9 | 0% | P33032 |
Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Adenosine deaminase, Melanocortin receptor 4, Melanocortin receptor 4, Melanocyte-stimulating hormone receptor, Melanocortin receptor 3, Melanocyte-stimulating hormone receptor, Melanocortin receptor 5, Melanocortin receptor 5, Melanocortin receptor 3, Melanocortin receptor 3.
Bioactivity
ChEMBL activities: 229 potent at pChembl ≥ 5 of 229 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| Q01727 | 11 | EC50 | 0.01 | nM | CHEMBL_ACT_18407664 |
| Q01727 | 11 | EC50 | 0.01 | nM | CHEMBL_ACT_19058644 |
| Q01727 | 11 | EC50 | 0.01 | nM | CHEMBL_ACT_22898089 |
| Q01727 | 11 | EC50 | 0.01 | nM | CHEMBL_ACT_25595923 |
| Q01727 | 10.85 | EC50 | 0.01 | nM | CHEMBL_ACT_3009754 |
| Q01727 | 10.82 | EC50 | 0.01 | nM | CHEMBL_ACT_17968722 |
| MC4R | 10.77 | EC50 | 0.02 | nM | CHEMBL_ACT_845198 |
| MC4R | 10.77 | EC50 | 0.02 | nM | CHEMBL_ACT_947080 |
| Q01727 | 10.74 | EC50 | 0.02 | nM | CHEMBL_ACT_1504205 |
| Q01727 | 10.74 | EC50 | 0.02 | nM | CHEMBL_ACT_5302258 |
| Q01727 | 10.7 | EC50 | 0.02 | nM | CHEMBL_ACT_18240726 |
| MC4R | 10.7 | EC50 | 0.02 | nM | CHEMBL_ACT_401816 |
| Q01727 | 10.68 | EC50 | 0.02 | nM | CHEMBL_ACT_18189764 |
| Q01727 | 10.64 | EC50 | 0.02 | nM | CHEMBL_ACT_1842217 |
| Q01727 | 10.64 | EC50 | 0.02 | nM | CHEMBL_ACT_29222669 |
| MC1R | 10.64 | EC50 | 0.02 | nM | CHEMBL_ACT_845196 |
| MC1R | 10.64 | EC50 | 0.02 | nM | CHEMBL_ACT_947078 |
| Q01727 | 10.52 | EC50 | 0.03 | nM | CHEMBL_ACT_1264308 |
| Q01727 | 10.52 | EC50 | 0.03 | nM | CHEMBL_ACT_16577764 |
| P41149 | 10.52 | EC50 | 0.03 | nM | CHEMBL_ACT_5302285 |
| Q01727 | 10.49 | EC50 | 0.03 | nM | CHEMBL_ACT_1507861 |
| Q01727 | 10.42 | EC50 | 0.04 | nM | CHEMBL_ACT_404854 |
| Q01727 | 10.42 | EC50 | 0.04 | nM | CHEMBL_ACT_575718 |
| Q01727 | 10.42 | EC50 | 0.04 | nM | CHEMBL_ACT_650330 |
| Q01727 | 10.4 | EC50 | 0.04 | nM | CHEMBL_ACT_18226003 |
| MC1R | 10.34 | Ki | 0.05 | nM | CHEMBL_ACT_10992016 |
| Q01727 | 10.34 | EC50 | 0.05 | nM | CHEMBL_ACT_189933 |
| Q01727 | 10.3 | EC50 | 0.05 | nM | CHEMBL_ACT_12653184 |
| Q01727 | 10.29 | EC50 | 0.05 | nM | CHEMBL_ACT_19485471 |
| P41149 | 10.21 | EC50 | 0.06 | nM | CHEMBL_ACT_1842241 |
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
7 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 |
|---|---|---|---|
| erythropoietic protoporphyria | 4 | MONDO:0001676 | MONDO:0001676 |
| vitiligo | 2 | MONDO:0008661 | EFO:0004208 |
| urticaria | 2 | MONDO:0005492 | EFO:0005531 |
| acne | 2 | MONDO:0011438 | EFO:0003894 |
| xeroderma pigmentosum | 2 | MONDO:0019600 | MONDO:0019600 |
| variegate porphyria | 2 | MONDO:0008297 | MONDO:0008297 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 21.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 12 |
| PHASE3 | 6 |
| PHASE1 | 2 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06109649 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study to Compare the Efficacy and Safety of SCENESSE and Narrow-Band Ultraviolet (NB-UVB) Light Versus NB-UVB Light Alone in Patients With Vitiligo |
| NCT00979745 | PHASE3 | COMPLETED | Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP) |
| NCT01605136 | PHASE3 | COMPLETED | Phase III Confirmatory Study in Erythropoietic Protoporphyria |
| NCT04053270 | PHASE3 | COMPLETED | Multicentre Phase III Erythropoietic Protoporphyria Study |
| NCT04578496 | PHASE3 | COMPLETED | A Safety Extension Study in Patients With Erythropoietic Protoporphyria (EPP) |
| NCT04704713 | PHASE3 | COMPLETED | Afamelanotide in Patients Suffering From Polymorphic Light Eruption (PLE) |
| NCT00829192 | PHASE2 | UNKNOWN | Phase II AK Study in Organ Transplant Patients |
| NCT00859534 | PHASE2 | COMPLETED | Phase II Solar Urticaria (SU) Pilot Study |
| NCT01097044 | PHASE2 | COMPLETED | Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP) |
| NCT01382589 | PHASE2 | COMPLETED | Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Light in the Treatment of Nonsegmental Vitiligo |
| NCT04425746 | PHASE2 | COMPLETED | Afamelanotide as Adjunctive Therapy in Patients Undergoing Photodynamic Therapy (PDT) Utilising Porfimer Sodium |
| NCT04525157 | PHASE2 | COMPLETED | Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Phototherapy in the Treatment of Nonsegmental Vitiligo (NSV) |
| NCT04943159 | PHASE2 | COMPLETED | Afamelanotide in Patients Suffering With Acne Vulgaris |
| NCT04962503 | PHASE2 | COMPLETED | A Proof of Concept Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS) |
| NCT05159752 | PHASE2 | UNKNOWN | A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum (XP) |
| NCT05210582 | PHASE2 | UNKNOWN | A Study to Assess the Changes in Pigmentation and Safety of Afamelanotide in Patients With Vitiligo on the Face |
| NCT05370235 | PHASE2 | UNKNOWN | A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum C and V |
| NCT05854784 | PHASE2 | COMPLETED | Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP) |
| NCT01430195 | PHASE1 | COMPLETED | Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Light in the Treatment of Nonsegmental Vitiligo (NSV) |
| NCT05368857 | PHASE1 | COMPLETED | DNA Repair Capacity of Afamelanotide on Ultraviolet Radiation-induced DNA Damage in Healthy Volunteers |
| NCT00472901 | Not specified | COMPLETED | Phase III Trial of CUV1647 in Polymorphic Light Eruption (PLE) |
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.
173 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| SETMELANOTIDE | 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: erythropoietic protoporphyria
- Drugs: Setmelanotide, 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