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Melanocortin-4 receptor (MC4R) agonist peptide

Setmelanotide

Setmelanotide is a synthetic cyclic octapeptide that selectively activates the melanocortin-4 receptor (MC4R), a signaling hub in the brain's appetite pathway.

By The Peptides Codex Editorial TeamIndividual review date not recorded

Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.

Length
8 aa
Class
Melanocortin-4 receptor (MC4R) agonist peptide
Function
Selective activation of the MC4 receptor in appetite pathways
Context
Prescription medicine approved for rare genetic conditions

A cyclic MC4R agonist approved for specific rare genetic disorders.

Also known as: Imcivree · RM-493

Part of the Metabolic & GLP-1 peptides cluster

Overview

Setmelanotide is a synthetic cyclic octapeptide that selectively activates the melanocortin-4 receptor (MC4R), a signaling hub in the brain's appetite pathway. Sold as Imcivree, it is an approved prescription medicine for certain rare genetic conditions. This page is educational and not medical advice.

Source & context

Biological / chemical source: Synthetic cyclic octapeptide

Primary research or clinical context: Prescription medicine approved for rare genetic conditions

Receptor target

The MC4 receptor sits within the leptin-melanocortin pathway that helps regulate energy balance. Setmelanotide is engineered as a cyclic, disulfide-containing octapeptide to bind MC4R with high selectivity. Its design reflects decades of melanocortin peptide chemistry aimed at receptor specificity.

Approval and status

Setmelanotide received FDA approval in 2020 and EU approval in 2021 for narrowly defined rare genetic disorders, and is a prescription-only therapeutic. It is used strictly under specialist supervision. This summary describes the peptide and its target for educational purposes and makes no therapeutic claims.

Sequence

One-letter sequence commonly cited for Setmelanotide (educational; isoforms and modifications may differ):

RCAHFRWC

RCAHFRWC

Setmelanotide8 aa · C49H68N18O9S2 · ≈ 1,117.3 DaPEPTIDESCODEX.COMN-terminus →→ C-terminusR+1C2A3H4F5R+6W7C8nonpolarpolaracidicbasicGly / Pronon-canonical (X)Hydropathy (Kyte–Doolittle): ▮ hydrophobic (cyan) / ▮ hydrophilic (rose) · Side-chain charge at pH 7: + / −
Setmelanotide — Structure cardDownload SVG
R1C2A3H4F5R6W7C8
Helical wheel projection

Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.

Analyze sequences in the playground →

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.

Molecular form
Setmelanotide (source record; form not independently established)
Species
Not established by this molecular identity audit
Termini (N / C)
Not specified / Not specified

Average reference mass

Reference policy updated: 2026-10-05

Molecular formula
C49H68N18O9S2
Average reference mass
≈ 1,117.3
Status
Approved medicine in at least one jurisdiction (IUPHAR record)
Identifiers

Chemistry values: IUPHAR/BPS Guide to Pharmacology, PubChem · fetched 2026-10-01.

Clinical development snapshot

ClinicalTrials.gov lists 27 registered studies with “Setmelanotide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.

Registered studies
27
Highest phase reached
Phase 4
Active in latest 100
5
Most recent update
2026-08-10
Most recently updated studies
NCTTitlePhaseStatusUpdated
NCT05774756A Trial of Setmelanotide in Acquired Hypothalamic ObesityPhase 3active not recruiting2026-08-10
NCT05093634EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R PathwayPhase 3completed2026-08-06
NCT07496463Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)Phase 2enrolling by invitation2026-07-23
NCT06596135Open-Label Extension Study of SetmelanotidePhase 3completed2026-07-15
NCT07674290Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic ObesityPhase 4recruiting2026-06-29
NCT06760546A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)Phase 3recruiting2026-02-12
See all on ClinicalTrials.gov →
Concentration math

Setmelanotide — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Setmelanotide (source record; form not independently established)Average reference mass: 1,117.3 Da

Syringe graduation
Solution concentration
5 mg/mL5,000 mcg/mL
mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Setmelanotide calculator on its own page →

FAQ about Setmelanotide

What is Setmelanotide?+

Setmelanotide is a synthetic cyclic octapeptide that selectively activates the melanocortin-4 receptor (MC4R), a signaling hub in the brain's appetite pathway. Sold as Imcivree, it is an approved prescription medicine for certain rare genetic conditions. This page is educational and not medical advice.

What Canadian product status is recorded for Setmelanotide?+

Canadian product status for Setmelanotide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Setmelanotide?+

Setmelanotide is commonly described as approximately 8 amino acids (Melanocortin-4 receptor (MC4R) agonist peptide).

Related peptides

Thymalin
Thymus-derived polypeptide complex (mixture)
Thymalin is a polypeptide complex extracted from thymus tissue and studied as an immunomodulatory 'thymic bioregulator.' Developed in the former USSR, it appears in immune and aging research, mostly outside Western regulatory systems. It is not authorized by Health Canada.
BPC-157
Research pentadecapeptide (gastric-juice-derived sequence)
BPC-157 (Body Protection Compound-157) is a synthetic 15-residue peptide, GEPPPGKPADDAGLV, derived from a sequence found in human gastric juice. Hundreds of rodent studies, most from a single Zagreb group, report accelerated healing of tendon, muscle, ligament, gut and skin injuries via VEGFR2, nitric-oxide and ERK1/2 pathways. Human evidence is limited to a small safety study and a retrospective chart review; the first phase 2 efficacy trial began recruiting in 2026. It is not approved anywhere and the FDA barred it from compounding in 2023.
TB-500
Synthetic thymosin β4 fragment (research peptide)
TB-500 is the synthetic, N-acetylated heptapeptide Ac-Leu-Lys-Lys-Thr-Glu-Thr-Gln (Ac-LKKTETQ), corresponding to residues 17–23 of thymosin β4, the protein's actin-binding motif. It first appeared as a veterinary preparation and is sold as a research chemical; its metabolism has been characterised in rats. A 2026 rat tendon study reported benefits with vendor-labelled TB-500 whose sequence was not characterized, so it does not establish efficacy of Ac-LKKTETQ. The fragment has no published human efficacy data. No product-specific authorization record has been verified in this profile; human trial registration does not establish approval. Its first registered human trial began recruiting in 2026.
Tirzepatide
Incretin dual agonist
Tirzepatide is a 39-amino-acid synthetic peptide (C225H348N48O68, ≈4,814 Da) that activates both the GIP and GLP-1 receptors. Its backbone is derived from GIP, with an exendin-4-like C-terminal tail, Aib residues at positions 2 and 13, and a C20 fatty diacid on Lys20 that binds albumin for a half-life of about 5 days. Approved as Mounjaro (type 2 diabetes, 2022) and Zepbound (weight management, 2023; obstructive sleep apnoea, 2024).

References & further reading

  1. 1.Haqq et al. (2022). Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol
  2. 2.Markham (2021). Setmelanotide: First Approval. Drugs
  3. 3.Roth et al. (2024). Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol
  4. 4.Miller et al. (2026). Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med
  5. 5.Clément et al. (2020). Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol
  6. 6.Collet et al. (2017). Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Mol Metab
  7. 7.Argente et al. (2025). Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol
  8. 8.Pressley et al. (2022). Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity. J Pharm Technol
  9. 9.PubChem — compound summary for Setmelanotide (CID 11993702)
  10. 10.Wikipedia — Setmelanotide
Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.
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