Target family: Melanocortin receptors (type: gpcr)
Target: MC<sub>5</sub> receptor

Ligand: [125I]NDP-MSH (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 8.6 pKd
Reference (Journal): Co-operative regulation of ligand binding to melanocortin receptor subtypes: evidence for interacting binding sites.
Published in: Eur J Pharmacol

Ligand: SHU9119 (Peptide)
Interaction type: Agonist
Action: Partial agonist
Ligand approved: no
Median affinity: 9 pKd
Reference (Journal): Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119.
Published in: Neuropeptides

Ligand: setmelanotide (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2020), EMA (2021)
Primary target: no
Median affinity: 6.369999885559082 pKi
Reference (Journal): Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice.
Published in: Peptides

Ligand: PG-901 (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 10.5 pIC50
Reference (Journal): Structure-activity studies of the melanocortin peptides: discovery of potent and selective affinity antagonists for the hMC3 and hMC4 receptors.
Published in: J Med Chem

Ligand: MT-II (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 9 pIC50
Reference (Journal): The role of melanocortins in body weight regulation: opportunities for the treatment of obesity.
Published in: Eur J Pharmacol

Ligand: HS024 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.5 pKd
Reference (Journal): Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo.
Published in: Endocrinology

Ligand: bremelanotide (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2019)
Primary target: no
Median affinity: 7.769999980926514 pKi
Reference (Journal): Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective α-melanocyte-stimulating hormone (α-MSH) analogues.
Published in: J Med Chem

Ligand: α-MSH (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 6.9 pKd
Reference (Journal): The role of melanocortins in body weight regulation: opportunities for the treatment of obesity.
Published in: Eur J Pharmacol

Ligand: agouti-related protein (Peptide)
Interaction type: Antagonist
Action: Inverse agonist
Ligand approved: no
Median affinity: 6.5 pIC50
Reference (Journal): Characterization of Agouti-related protein binding to melanocortin receptors.
Published in: Mol Endocrinol

Ligand: agouti (Peptide)
Interaction type: Antagonist
Action: Inverse agonist
Ligand approved: no
Median affinity: 4.9 pKd
Reference (Journal): Melanocortin receptor binding determinants in the agouti protein.
Published in: Biochemistry

Ligand: afamelanotide (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: EMA (2014), FDA (2019)
Median affinity: 9 pIC50
Reference (Journal): The role of melanocortins in body weight regulation: opportunities for the treatment of obesity.
Published in: Eur J Pharmacol

Ligand: ACTH (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (1950)
Primary target: no
Median affinity: 5 pKi
Reference (Journal): Characterisation of melanocortin receptor subtypes by radioligand binding analysis.
Published in: Eur J Pharmacol

Ligand: Ac-c[Cys-Glu-His-D-Phe-Arg-Trp-D-Cys]-Pro-Pro-Lys-Asp-NH2 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8 pIC50
Reference (Journal): Structure-activity relationships of novel cyclic alpha-MSH/beta-MSH hybrid analogues that lead to potent and selective ligands for the human MC3R and human MC5R.
Published in: J Med Chem