Target family: Melanocortin receptors (type: gpcr)
Target: MC<sub>4</sub> receptor

Ligand: THIQ (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Primary target: no
Median affinity: 8.899999618530273 pIC50
Reference (Journal): Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist.
Published in:  J Med Chem

Ligand: [125I]SHU9119 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.2 pKd
Reference (Journal): Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity.
Published in: J Pharmacol Exp Ther

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

Ligand: [125I]NDP-MSH (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Characterisation of melanocortin receptor subtypes by radioligand binding analysis.
Published in: Eur J Pharmacol

Ligand: SHU9119 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.
Published in: Eur J Pharmacol

Ligand: SHU9119 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKi
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: 8.569999694824219 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: setmelanotide (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2020), EMA (2021)
Primary target: no
Median affinity: 8.680000305175781 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: setmelanotide (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2020), EMA (2021)
Primary target: no
Median affinity: 8.680000305175781 pKi
Reference (Journal): 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.
Published in: Lancet Diabetes Endocrinol

Ligand: RY764 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 8.1 pIC50
Reference (Journal): Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist.
Published in: Bioorg Med Chem Lett

Ligand: PG-901 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.1 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:  pKi
Reference (Journal): Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.
Published in: Eur J Pharmacol

Ligand: MT-II (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Molecular determinants of ligand binding to the human melanocortin-4 receptor.
Published in: Biochemistry

Ligand: MT-II (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Design of potent linear &alpha;-melanotropin 4-10 analogues modified in positions 5 and 10.
Published in: J Med Chem

Ligand: MCL0129 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 10.1 pKd
Reference (Journal): Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor.
Published in: J Pharmacol Exp Ther

Ligand: MBP10 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 10 pIC50
Reference (Journal): Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro.
Published in: J Med Chem

Ligand: HS024 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 9.5 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: HS014 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.5 pKi
Reference (Journal): Discovery of novel melanocortin4 receptor selective MSH analogues.
Published in: Br J Pharmacol

Ligand: HS014 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.5 pKd
Reference (Journal): Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist.
Published in: Br J Pharmacol

Ligand: bremelanotide (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2019)
Primary target: no
Median affinity: 9.600000381469727 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: bremelanotide (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (2019)
Primary target: no
Median affinity: 9.600000381469727 pKi
Reference (Journal): Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials.
Published in: Obstet Gynecol

Ligand: α-MSH (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Molecular determinants of ligand binding to the human melanocortin-4 receptor.
Published in: Biochemistry

Ligand: α-MSH (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.
Published in: Eur J Pharmacol

Ligand: agouti-related protein (Peptide)
Interaction type: Antagonist
Action: Inverse agonist
Ligand approved: no
Median affinity: 9.3 pIC50
Reference (Journal): ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors.
Published in: Biochem Biophys Res Commun

Ligand: agouti (Peptide)
Interaction type: Antagonist
Action: Inverse agonist
Ligand approved: no
Median affinity: 7.3 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:  pKi
Reference (Journal): Molecular determinants of ligand binding to the human melanocortin-4 receptor.
Published in: Biochemistry

Ligand: afamelanotide (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: EMA (2014), FDA (2019)
Median affinity:  pKi
Reference (Journal): Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.
Published in: Eur J Pharmacol

Ligand: afamelanotide (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: yes
Approval source: EMA (2014), FDA (2019)
Median affinity:  pKi
Reference (Journal): 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.
Published in: Proc Natl Acad Sci USA

Ligand: ACTH (Peptide)
Interaction type: Agonist
Action: Agonist
Ligand approved: yes
Approval source: FDA (1950)
Primary target: no
Median affinity: 6.159999847412109 pKi
Reference (Journal): Characterisation of the melanocortin 4 receptor by radioligand binding.
Published in: Pharmacol Toxicol