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Setmelanotide / Studies
Synthetic analog · 8 amino acids · 1,117.3 Da

Setmelanotide studies and research data

PepBank has 62 setmelanotide studies with results. 60 of them gave setmelanotide, with 332 results, grouped by what the studies measured. In each group, results from studies in people come first. Data as of 2026-10-30.

Searches 332 results and 132 papers. Newer studies from Europe PMC

Results in people
276
83% of 332 results
Results in animals
40
12% of 332 results
Results in lab cells
16
5% of 332 results
From computer models
0
0% of 332 results
The molecule

Setmelanotide identity

Identifiers, parent molecule, targets and development stage, from curated data.

Setmelanotide is a cyclic eight-residue melanocortin-4 receptor agonist. Its label covers selected genetic and acquired hypothalamic obesity conditions.

Kind
Synthetic analog · 8 residues
Identifiers
ChEMBLCHEMBL3301624 (opens in a new tab)PubChem CID11993702 (opens in a new tab)UNIIN7T15V1FUY (opens in a new tab)DrugBankDB11700 (opens in a new tab)CAS920014-72-8
Parent
Analog of Alpha-melanocyte-stimulating hormoneThe US label identifies setmelanotide as an eight-residue cyclic analog of endogenous alpha-MSH. P01189 encodes its human POMC precursor. No contiguous parent segment is assigned to this modified analog.
Development
Approved in the US and EU (Imcivree, 2020)Rhythm PharmaceuticalsImcivree is approved in the US and EU. Approval applies to the specified formulation, patient groups, and indications. Source (opens in a new tab)

Targets

Molecular targets with action and evidence source
TargetActionEvidence
Melanocortin 4 receptorMC4RP32245 (opens in a new tab)AgonistOfficial prescribing information, mechanism of actionSource (opens in a new tab)

Sequence and structure

Residues, differences from the parent, calculated properties and 3D structure. Source values and calculated values are shown separately.

Sequence

8 amino acids · 2 modifications · 1 disulfide bond

Residues 1 to 8:
RCHRWC
  • HydrophobicA V I L M
  • AromaticF W Y
  • PositiveK R H
  • SpecialC G P
  • Modified residue
  • Disulfide partner

Modifications

Residue 3
D-amino acid
D-Ala
Residue 5
D-amino acid
D-Phe
Cys2–Cys8
Disulfide bond

Alignment to Alpha-melanocyte-stimulating hormone

Calculated from the two sequences. Curated notes are shown as given.

3 of 8 aligned residues identical (38%) · 3 substitutions · 2 non-canonical residues · Alpha-melanocyte-stimulating hormone 3–10

  • Top row: Alpha-melanocyte-stimulating hormone (parent)
  • Bottom row: Setmelanotide
HRW
  • Same as parent
  • Substituted
  • Non-canonical or D-form
  • Added
  • Gap
  • Modified side chain or end
  • Parent context

Differences from the parent

  1. 1Parent 3 · analog 1Ser → Arg · Substitution
  2. 2Parent 4 · analog 2Met → Cys · Substitution
  3. 3Parent 5 · analog 3Glu → D-Ala · D-amino acidD-Ala
  4. 4Parent 7 · analog 5Phe → D-Phe · D-amino acidD-Phe
  5. 5Parent 10 · analog 8Gly → Cys · Substitution

Basis: The US label identifies setmelanotide as an eight-residue cyclic analog of endogenous alpha-MSH. P01189 encodes its human POMC precursor. No contiguous parent segment is assigned to this modified analog.

Calculated from the two sequences with @pepdb/chem alignToParent (ungapped unless a gap scores higher). The record’s curated notes are shown as given.

Properties

From identity sources

Formula
C49H68N18O9S2
Molecular weight
1,117.3 g/mol
Monoisotopic mass
1,116.4858 Da

Calculated from the sequence

Average mass
1,117.31 Da
Sum of ExPASy residue masses + water + N-acetyl, C-amide, 1 disulfide · ExPASy Compute pI/Mw; FindMod
Monoisotopic mass
1,116.4859 Da
Sum of ExPASy residue masses + water + N-acetyl, C-amide, 1 disulfide · ExPASy FindMod
Isoelectric point (pI)
Not calculated
The net charge does not reach zero between pH 0 and 14 (the peptide has no acidic or no basic group in this model).
Net charge at pH 7.4
2.11
Henderson-Hasselbalch, EMBOSS pKa set · EMBOSS iep, Epk.dat
GRAVY (hydropathy)
−0.438
Mean Kyte-Doolittle hydropathy · Kyte and Doolittle 1982
Negative: hydrophilic on average.
Extinction coefficient, 280 nm (Cys reduced)
5,500 M⁻¹ cm⁻¹
5500 x Trp + 1490 x Tyr · Pace et al. 1995 (ExPASy ProtParam)
Extinction coefficient, 280 nm (all Cys as cystines)
5,625 M⁻¹ cm⁻¹
5500 x Trp + 1490 x Tyr + 125 x cystine · Pace et al. 1995 (ExPASy ProtParam)
Instability index
56.78
Dipeptide instability weights (DIWV) · Guruprasad et al. 1990
Above 40: classed as possibly unstable (ExPASy).
Aliphatic index
12.5
Mole % A + 2.9 V + 3.9 (I + L) · Ikai 1980
Boman index
3.10 kcal/mol
Mean solubility value (negated) · Boman 2003
Above 2.48: high protein-binding potential (Boman).
Hydrophobic moment (μH)
Not calculated
The sequence is too short for this method.
  • D-amino acids have the same mass and charge as L forms. Hydrophobicity scales were measured on L forms.
  • Defined and validated for proteins; use with care for short peptides.
  • Assumes an ideal alpha helix. Many short peptides are not helical.

@pepdb/chem 0.2.0 · EMBOSS pKa set · ExPASy residue masses

Net charge by pH

Net charge at pH 7.4: 2.11

Point or use arrow keys

Net charge of Setmelanotide from pH 0 to 14 (EMBOSS pKa set). Net charge at pH 7.4: 2.11.−10+1+2+302468101214pHNet chargepH 7.4

Henderson-Hasselbalch, EMBOSS pKa set, N-acetyl, C-amide, 1 disulfide. Calculated, not measured.

Show as table
pHNet charge
03.00
13.00
23.00
33.00
43.00
52.97
62.76
72.24
82.03
92.00
101.99
111.94
121.52
130.48
140.06

Composition

  • Hydrophobic13% (1)
  • Aromatic25% (2)
  • Positive38% (3)
  • Special25% (2)

8 residues. Each residue counts in one class; F and W count as aromatic.

A Ala1 · 13%
I Ile0 · 0%
L Leu0 · 0%
M Met0 · 0%
V Val0 · 0%
F Phe1 · 13%
W Trp1 · 13%
Y Tyr0 · 0%
H His1 · 13%
K Lys0 · 0%
R Arg2 · 25%
D Asp0 · 0%
E Glu0 · 0%
N Asn0 · 0%
Q Gln0 · 0%
S Ser0 · 0%
T Thr0 · 0%
C Cys2 · 25%
G Gly0 · 0%
P Pro0 · 0%

3D structure

PredictedAlphaFold DB · P01189

Loads the 3D viewer (3Dmol.js, about 150 KB) and the model file from AlphaFold DB (EMBL-EBI).

  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

Predicted model of the whole UniProt entry P01189, not an experimental structure of Setmelanotide.

AlphaFold DB, EMBL-EBI and Google DeepMind · CC BY 4.0

2D structure

Draws the structure in your browser with RDKit (about 2.3 MB, loaded once).

SMILES fromPubChem CID 11993702(opens in a new tab)

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
Results by area

What the studies measured

People first in each area, then animals, then lab cells. Counts are exact and come from studies that gave the peptide.

Trials and papers
Status and safety
Data