Protein / target

Melanocyte-stimulating hormone receptor

Encoded byMC1RQ01726Homo sapiensSwiss-Prot

UniProt: Q01726 Ensembl: ENSG00000258839 HGNC: HGNC:6929 NCBI Gene: 4157

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Advanced Clinical

Protein at a glance

Biological role

Melanocyte-stimulating hormone receptor

Strongest disease association

Skin Neoplasms

Via encoding gene MC1R · Genetic evidence · score 0.88

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein.

View complete UniProt function annotation

G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein (PubMed:11442765, PubMed:11707265, PubMed:1325670, PubMed:1516719, PubMed:8463333). Upon activation, MC1R couples with the G(s) protein, stimulating adenylate cyclase and activating the cAMP-dependent signaling pathway. This activation promotes melanogenesis, resulting in the production of eumelanin (black/brown) and pheomelanin (red/yellow) in melanocytes (PubMed:11707265, PubMed:1325670, PubMed:16463023, PubMed:19737927, PubMed:31097585, PubMed:34453129). MC1R interacts with G protein-coupled receptor opsin 3/OPN3, which couples to G(i) proteins and inhibits the alpha-MSH-induced cAMP response, thereby reducing melanin synthesis (PubMed:31097585). Binding to Agouti/ASP precludes alpha-MSH-induced signaling, thereby downregulating melanogenesis (By similarity). Additionally, interaction with MGRN1 displaces the G(s) protein, further suppressing MC1R signaling (PubMed:19737927)

Subcellular location

Cell membrane

Domains and Gene Ontology detail (22)

Gene Ontology

Ccytoplasm
Cplasma membrane
Fcorticotropin receptor activity
FG protein-coupled peptide receptor activity
Fhormone binding
Fmelanocortin receptor activity
Fmelanocyte-stimulating hormone receptor activity
Fmetal ion binding
Fubiquitin protein ligase binding
Padenylate cyclase-activating G protein-coupled receptor signaling pathway
PG protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
Pintracellular signal transduction

317 aa · 35 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingUniProt · GO

View supporting evidence

G protein-coupled signalling

·G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and…
·G protein-coupled peptide receptor activity
·adenylate cyclase-activating G protein-coupled receptor signaling pathway
·G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messen…

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Protoporphyria, Erythropoietic1 medicine

afamelanotide

2 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

afamelanotide

Narrow target profileApprovedAgonist

Melanocortin receptor 1 agonist

Indicated for Protoporphyria, Erythropoietic

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene MC1R

Gene-level evidence surfaced through the gene MC1Rthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Skin Neoplasms

0.89Well supported

Genetic evidence dominant · Open Targets 0.58

Hair color

0.85Well supported

Genetic evidence dominant · Open Targets 0.52

Actinic keratosis

0.85Well supported

Genetic evidence dominant · Open Targets 0.52

Basal cell carcinoma

0.84Well supported

Genetic evidence dominant · Open Targets 0.51

Skin Diseases

0.84Well supported

Genetic evidence dominant · Open Targets 0.51

View evidence synthesis (5)

Skin NeoplasmsWell supported

0.89

agreement 0.75–1.00

Genetic90%Literature10%

Open Targets aggregate 0.58 · 2 independent evidence families

Hair colorWell supported

0.85

agreement 0.73–0.97

Genetic100%

Open Targets aggregate 0.52 · 1 independent evidence family

Actinic keratosisWell supported

0.85

agreement 0.71–0.99

Genetic99%Literature1%

Open Targets aggregate 0.52 · 2 independent evidence families

Basal cell carcinomaWell supported

0.84

agreement 0.70–0.98

Genetic97%Literature3%

Open Targets aggregate 0.51 · 2 independent evidence families

Skin DiseasesWell supported

0.84

agreement 0.70–0.97

Genetic96%Literature4%

Open Targets aggregate 0.51 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Skin Neoplasms0.58

Cutaneous melanoma0.56

Actinic keratosis0.52

Hair color0.52

Skin Diseases0.51

Basal cell carcinoma0.51

Drug development

4 compounds recorded · 2 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (4)

AFAMELANOTIDEApproval

MODIMELANOTIDEPhase 2

DERSIMELAGONPhase 3

AFAMELANOTIDE ACETATEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and High-Quality Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (9)

SM · Advanced ClinicalSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Phase III, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)PHASE3

COMPLETED · via afamelanotide · NCT01605136

A Phase III, Safety Extension Study in Patients With Erythropoietic Protoporphyria (EPP)PHASE3

COMPLETED · via afamelanotide · NCT04578496

A Phase III, Randomised, Double Blind, Placebo Controlled, Parallel Group Study, to Evaluate the Safety and Efficacy of Subcutaneous Implants of Afamelanotide (16 mg) in Patients Suffering From Polymorphic Light Eruption (PLE)PHASE3

COMPLETED · via afamelanotide · NCT04704713

A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)PHASE3

COMPLETED · via afamelanotide · NCT00979745

View all trials (15)

A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 Implants in Patients With Erythropoietic Protoporphyria (EPP)PHASE3

COMPLETED · via afamelanotide · NCT04053270

Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP)-Related Skin Disease.PHASE2

COMPLETED · via afamelanotide · NCT05854784

An Open Label, Phase II Study to Assess the Changes in Pigmentation and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants in the Treatment of Vitiligo on the FacePHASE2

UNKNOWN · via afamelanotide · NCT05210582

A Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety and Efficacy of Subcutaneous Implants of Afamelanotide in Patients With Xeroderma Pigmentosum C and V (XPC and XPV)PHASE2

UNKNOWN · via afamelanotide · NCT05370235

A Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety and Efficacy of Subcutaneous Implants of Afamelanotide in Patients With Xeroderma Pigmentosum (XP)PHASE2

UNKNOWN · via afamelanotide · NCT05159752

A Proof of Concept, Phase IIa, Open Label Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS) Due to Distal [M2 Segment and Beyond] Arterial Large Vessel Occlusion (LVO) or Perforator Occlusion and Who Are Ineligible for Intravenous Thrombolysis (IVT) or Endovascular Thrombectomy (EVT)PHASE2

COMPLETED · via afamelanotide · NCT04962503

A Two-Arm, Randomized, Double-Blind, Phase IIb Study to Compare the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants Plus Narrow-Band Ultraviolet B (NB-UVB) Light Source With Narrow-Band Ultraviolet B (NB-UVB) Light Source in the Treatment of Nonsegmental Vitiligo AND A Single-Arm, Open Label, Phase IIb Study to Evaluate the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants Plus Narrow-Band Ultraviolet B (NB-UVB) Light Source in the Treatment of Nonsegmental VitiligoPHASE2

COMPLETED · via afamelanotide · NCT04525157

A Phase II Randomised Pilot Study to Compare the Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants and Narrow-Band Ultraviolet B (NB-UVB) Light in the Treatment of Nonsegmental VitiligoPHASE2

COMPLETED · via afamelanotide · NCT01382589

A Phase II, Randomised, Open Label Pilot Study to Evaluate the Efficacy and Safety of Two Dosage Regimens of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Mild to Moderate Acne VulgarisPHASE2

COMPLETED · via afamelanotide · NCT04943159

A Phase II, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)PHASE2

COMPLETED · via afamelanotide · NCT01097044

A Phase II, Open Label Pilot Study to Evaluate the Safety and Efficacy of A Bioresorbable Subcutaneous Implant of CUV1647 in Patients With Solar Urticaria (SU)PHASE2

COMPLETED · via afamelanotide · NCT00859534

A Phase II, Multicentre, Double-blind, Placebo Controlled, Pilot Study to Evaluate the Safety and Efficacy of CUV1647 (Afamelanotide) as Adjunctive Therapy in Patients Undergoing Photodynamic Therapy (PDT) Utilising Porfimer SodiumPHASE2

COMPLETED · via afamelanotide · NCT04425746

A Multicentre, Randomised, Double-Blind, Placebo Controlled, Phase II Study to Evaluate the Safety and Efficacy of Subcutaneous Bioresorbable Implants of Afamelanotide (CUV1647) for the Prophylactic Treatment of Pre-Cancerous Skin Lesions of the Head, Forearms and Hands in Immune Compromised, Organ Transplant Patients.PHASE2

UNKNOWN · via afamelanotide · NCT00829192

A Mechanistic Study to Evaluate Impact of Subcutaneous Implants of Afamelanotide on Ultraviolet Radiation-induced DNA Damage and DNA Repair Capacity in Healthy Volunteers With Skin Types I-IIIPHASE1

COMPLETED · via afamelanotide · NCT05368857

Proof of Concept Study to Compare Efficacy and Safety of Subcutaneous, Bioresorbable Afamelanotide Implants and Narrow-Band Ultraviolet B (NB-UVB) Light Versus NB-UVB Light Alone in the Treatment of Nonsegmental VitiligoPHASE1

COMPLETED · via afamelanotide · NCT01430195

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

Regulatory approval2014-12-22
Approval: Scenesse (EMA)
ema · regulatory · ema · via afamelanotide

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.