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MC4 receptor

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Target not currently curated in GtoImmuPdb

Target id: 285

Nomenclature: MC4 receptor

Family: Melanocortin receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 332 18q21.3 MC4R melanocortin 4 receptor 13,26
Mouse 7 184 18E1 Mc4r melanocortin 4 receptor
Rat 7 332 18p11 Mc4r melanocortin 4 receptor
Database Links Click here for help
Specialist databases
GPCRDB mc4r_human (Hs), mc4r_mouse (Mm), mc4r_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Melanocortin-4 Receptor (MC4R) in complex with SHU9119
PDB Id:  6W25
Ligand:  SHU9119
Resolution:  2.75Å
Species:  Human
References:  43
Associated Proteins Click here for help
Interacting Proteins
Name Effect References
melanocortin-2 receptor accessory protein 2 (MRAP2) Essential for receptor activity and sensitivity to ligands. 23
glucose-regulated protein 78 Chaperone: Involved in the internalization and trafficking of MC4R 42
Natural/Endogenous Ligands Click here for help
ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat}
agouti {Sp: Mouse}
agouti-related protein {Sp: Human}
β-MSH {Sp: Human}
α-MSH {Sp: Human, Mouse, Rat}
γ-MSH {Sp: Human, Mouse, Rat}
β-MSH {Sp: Mouse} , β-MSH {Sp: Rat}
Comments: β-MSH is the principal endogenous agonist. Endogenous antagonists are agouti and agouti-related protein. For representations of the rodent orthologues of these peptides see agouti (mouse), agouti (rat) and agouti-related protein (mouse).
Potency order of endogenous agonists (Human)
β-MSH (POMC, P01189) > α-MSH (POMC, P01189), ACTH (POMC, P01189) > γ-MSH (POMC, P01189)

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]NDP-MSH Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.4 – 8.9 pKd 20,31
pKd 8.4 – 8.9 (Kd 4x10-9 – 1.2x10-9 M) [20,31]
bremelanotide Peptide Approved drug Click here for species-specific activity table Hs Agonist 9.6 pKi 8
pKi 9.6 (Ki 2.5x10-10 M) [8]
Description: Inhibition of 125I-NDP-αMSH binding to membranes from BHK570 cells stably expressing human MC4 receptor.
setmelanotide Peptide Click here for species-specific activity table Hs Agonist 8.7 pKi 22
pKi 8.7 (Ki 2.1x10-9 M) [22]
afamelanotide Peptide Approved drug Click here for species-specific activity table Hs Full agonist 8.5 – 8.8 pKi 1,30,40
pKi 8.5 – 8.8 [1,30,40]
setmelanotide Peptide Rn Agonist 8.6 pKi 22
pKi 8.6 (Ki 2.7x10-9 M) [22]
MT-II Peptide Click here for species-specific activity table Hs Full agonist 8.2 – 8.8 pKi 1-2,40
pKi 8.2 – 8.8 [1-2,40]
α-MSH {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.4 – 8.0 pKi 1,40
pKi 7.4 – 8.0 [1,40]
ACTH {Sp: Human} Peptide Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 6.2 pKi 33
pKi 6.2 (Ki 6.93x10-7 M) [33]
THIQ Small molecule or natural product Hs Full agonist 8.9 pIC50 35
pIC50 8.9 (IC50 1.26x10-9 M) [35]
RY764 Small molecule or natural product Hs Full agonist 8.1 pIC50 41
pIC50 8.1 [41]
View species-specific agonist tables
Agonist Comments
The relative potency of melanocortin peptides at the MC4 is β-MSH>α-MSH=ACTH>γ-MSH [24].

Radioligands commonly used to study the MC4 are [125I]NDP-MSH, [125I]MT-II, [125I]SHU9119, [125I]AGRP(83-132).

RO27-3225 is a selective MC1R and MC4R agonist [4]. cAMP but no binding data were reported.

[125I]NDP-MSH, [125I]MT-II, [125I]SHU9119, [125I]Nle7-α-MSH are common radioligands used to study MC1, 3, 4 and MC 5.

MK-0493 has been reported to be a potent and selective agonist for this receptor [21].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MCL0129 Small molecule or natural product Hs Antagonist 10.1 pKd 6
pKd 10.1 [6]
HS024 Peptide Click here for species-specific activity table Hs Antagonist 9.5 pKd 17
pKd 9.5 [17]
[125I]SHU9119 Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.2 pKd 28
pKd 9.2 (Kd 7x10-10 M) [28]
HS014 Peptide Click here for species-specific activity table Hs Antagonist 8.5 pKd 36
pKd 8.5 (Kd 3.16x10-9 M) [36]
agouti {Sp: Mouse} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Mm Inverse agonist 7.3 pKd 18
pKd 7.3 [18]
SHU9119 Peptide Click here for species-specific activity table Hs Antagonist 9.4 – 9.6 pKi 1,32
pKi 9.4 – 9.6 [1,32]
HS014 Peptide Click here for species-specific activity table Hs Antagonist 8.5 pKi 34
pKi 8.5 (Ki 3.2x10-9 M) [34]
MBP10 Peptide Hs Antagonist 10.0 pIC50 3
pIC50 10.0 (IC50 1x10-10 M) [3]
agouti-related protein {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Inverse agonist 9.3 pIC50 12
pIC50 9.3 [12]
PG-901 Peptide Click here for species-specific activity table Hs Antagonist 8.1 pIC50 15
pIC50 8.1 [15]
View species-specific antagonist tables
Antagonist Comments
The pIC50 of full-length recombinant AGRP expressed in bacteria has been reported to be 7.06 [29].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  13,26
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
G protein (identity unknown) Other - See Comments
Comments:  Melanocortin activation of the MC4 mobilizes intracellular calcium via an incompletely understood pathway.
Non-G protein dependent transduction: Effector/response inwardly rectifying potassium channel, Kir7.1
References:  14,25
Tissue Distribution Click here for help
Pituitary gland.
Species:  Human
Technique:  PCR and hybridisation.
References:  7
Dermal papilla cells.
Species:  Human
Technique:  RT-PCR and immunofluorescence,
References:  5
Spinal cord: Intermediolateral cell column and dorsal horn.
Brain: Diencephalon neuroepithelia, telencephalon, lamina terminalis, spinal trigeminal nucleus.
Species:  Rat
Technique:  in situ hybridisation.
References:  27
Penis, spinal cord, hypothalamus, brainstem and pelvic ganglion.
Species:  Rat
Technique:  RT-PCR and RNase protection assay.
References:  38
Hypothalamus: Anteroventral periventricular, ventromedial preoptic, median preoptic, paraventricular, dorsomedial, and arcuate nuclei as well as the subfornical organ, dorsal hypothalamic, perifornical, and posterior hypothalamic areas.
Extrahypothalamic: Infralimbic and insular cortices, bed nucleus of the stria terminalis, central nucleus of the amygdala, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus (DMV), and intermediolateral nucleus of the spinal cord (IML).
Species:  Rat
Technique:  in situ hybridisation.
References:  19
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of Ca2+ in a HEK 293 cell line transfected with the MC4.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Mobilization of [Ca2+]i.
References:  25
Measurement of cAMP levels in cell lines transfected with the MC4 receptors.
Species:  Human
Tissue:  HEK 293 and COS cells.
Response measured:  Intracellular cAMP accumulation.
References:  13,26,39
Physiological Functions Click here for help
MC4 receptors are involved in the inhibition of feeding behaviour and the regulation of metabolism.
Species:  Mouse
Tissue:  In vivo
References:  9,16
The MC4 receptor is involved in sexual behaviour and male erectile function.
Species:  Mouse
Tissue:  In vivo.
References:  38
Physiological Consequences of Altering Gene Expression Click here for help
MC4 receptor knock-out mice become obese, hyperphagic, hyperinsulinemic, and hyperglycemic.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0002561 abnormal circadian phase PMID: 15596147 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005449 abnormal food intake PMID: 10971147 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
B6.129S4-Mc4r
MGI:99457  MP:0005449 abnormal food intake PMID: 15034587 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005449 abnormal food intake PMID: 16269339 
Mc4rtm1Lowl|Tg(Sim1-cre)1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692524  MGI:99457  MP:0005449 abnormal food intake PMID: 16269339 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0002078 abnormal glucose homeostasis PMID: 9019399 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0003313 abnormal locomotor activation PMID: 15596147 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005288 abnormal oxygen consumption PMID: 16269339 
Mc4rtm1Lowl|Tg(Sim1-cre)1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692524  MGI:99457  MP:0005288 abnormal oxygen consumption PMID: 16269339 
Htr2ctm1Knk|Mc4rtm1Lowl Htr2ctm1Knk/Y,Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6
MGI:96281  MGI:99457  MP:0006086 decreased body mass index PMID: 19036977 
Mc4rGlu3 Mc4rGlu3/Mc4rGlu3
C57BL/6J-Mc4r
MGI:99457  MP:0001262 decreased body weight PMID: 17143585 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0004985 decreased osteoclast cell number PMID: 15724149 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005290 decreased oxygen consumption PMID: 16269339 
Mc4rtm1Lowl|Tg(Sim1-cre)1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692524  MGI:99457  MP:0005290 decreased oxygen consumption PMID: 16269339 
Mc4r+|Mc4rGlu3 Mc4rGlu3/Mc4r+
involves: C57BL/6J
MGI:99457  MP:0001559 hyperglycemia PMID: 12955145 
Mc4r+|Mc4rGlu3 Mc4rGlu3/Mc4r+
involves: 129S6/SvEvTac
MGI:99457  MP:0001559 hyperglycemia PMID: 12955145 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001559 hyperglycemia PMID: 9019399 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001257 increased body length PMID: 16269339 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001264 increased body size PMID: 9019399 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001260 increased body weight PMID: 15596147  9019399 
Mc4rI194F Mc4rI194F/Mc4rI194F
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0001260 increased body weight PMID: 16720677 
Mc4r+|Mc4rI194F Mc4rI194F/Mc4r+
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0001260 increased body weight PMID: 16720677 
Mc4r+|Mc4rY302C Mc4rY302C/Mc4r+
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0001260 increased body weight PMID: 16720677 
Mc4rY302C Mc4rY302C/Mc4rY302C
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0001260 increased body weight PMID: 16720677 
Mc4rtm1Lowl|Tg(Sim1-cre)1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692524  MGI:99457  MP:0001260 increased body weight PMID: 16269339 
Mc4rGlu3 Mc4rGlu3/Mc4rGlu3
C57BL/6J-Mc4r
MGI:99457  MP:0001260 increased body weight PMID: 17143585 
Mc4r+|Mc4rGlu3 Mc4rGlu3/Mc4r+
C57BL/6J-Mc4r
MGI:99457  MP:0001260 increased body weight PMID: 17143585 
Mc4rm1Btlr Mc4rm1Btlr/Mc4rm1Btlr
C57BL/6J-Mc4r
MGI:99457  MP:0001260 increased body weight PMID: 17143585 
Mc3rtm1Lvp|Mc4rtm1Dhu Mc3rtm1Lvp/Mc3rtm1Lvp,Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6J
MGI:96929  MGI:99457  MP:0001260 increased body weight PMID: 10973258 
Mc4rtm1Dhu|Pomctm1Low Mc4rtm1Dhu/Mc4rtm1Dhu,Pomctm1Low/Pomctm1Low
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6
MGI:97742  MGI:99457  MP:0001260 increased body weight PMID: 12697680 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005605 increased bone mass PMID: 15724149 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0002079 increased circulating insulin level PMID: 9019399 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0002079 increased circulating insulin level PMID: 16269339 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005669 increased circulating leptin level PMID: 9019399 
Mc4rtm1Lowl|Tg(Sim1-cre)1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692524  MGI:99457  MP:0003960 increased lean body mass PMID: 16269339 
Mc4rGlu3 Mc4rGlu3/Mc4rGlu3
C57BL/6J-Mc4r
MGI:99457  MP:0005458 increased percent body fat PMID: 17143585 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0005658 increased susceptibility to diet-induced obesity PMID: 11369941 
Mc4r+|Mc4rGlu3 Mc4rGlu3/Mc4r+
involves: C57BL/6J
MGI:99457  MP:0005455 increased susceptibility to weight gain PMID: 12955145 
Mc4r+|Mc4rGlu3 Mc4rGlu3/Mc4r+
involves: 129S6/SvEvTac
MGI:99457  MP:0005455 increased susceptibility to weight gain PMID: 12955145 
Mc4rI194F Mc4rI194F/Mc4rI194F
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0005455 increased susceptibility to weight gain PMID: 16720677 
Mc4r+|Mc4rI194F Mc4rI194F/Mc4r+
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0005455 increased susceptibility to weight gain PMID: 16720677 
Mc4r+|Mc4rY302C Mc4rY302C/Mc4r+
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0005455 increased susceptibility to weight gain PMID: 16720677 
Mc4rY302C Mc4rY302C/Mc4rY302C
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0005455 increased susceptibility to weight gain PMID: 16720677 
Mc4rtm1Lowl|Tg(Nes-cre)1Kln Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Nes-cre)1Kln/0
involves: 129S4/SvJae * C57BL/6 * SJL
MGI:2176172  MGI:99457  MP:0002169 no abnormal phenotype detected PMID: 16269339 
Mc4rtm1Lowl|Tg(Zp3-cre)3Mrt Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Zp3-cre)3Mrt/0
involves: 129S4/SvJae * C57BL/6J * FVB/N
MGI:2176051  MGI:99457  MP:0002169 no abnormal phenotype detected PMID: 16269339 
Mc4rI194F Mc4rI194F/Mc4rI194F
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0001261 obese PMID: 16720677 
Mc4rY302C Mc4rY302C/Mc4rY302C
involves: C3HeB/FeJ * C57BL/6J
MGI:99457  MP:0001261 obese PMID: 16720677 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001261 obese PMID: 16269339 
Mc4rtm1Lowl|Tg(Sim1-cre)1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692524  MGI:99457  MP:0001261 obese PMID: 16269339 
Mc4rtm1Lowl|Tg(Sim1-cre)2Lowl Mc4rtm1Lowl/Mc4rtm1Lowl,Tg(Sim1-cre)2Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB
MGI:3692525  MGI:99457  MP:0001261 obese PMID: 16269339 
Mc4rGlu3 Mc4rGlu3/Mc4rGlu3
C57BL/6J-Mc4r
MGI:99457  MP:0001261 obese PMID: 17143585 
Mc4rm1Btlr Mc4rm1Btlr/Mc4rm1Btlr
C57BL/6J-Mc4r
MGI:99457  MP:0001261 obese PMID: 17143585 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001433 polyphagia PMID: 15596147  9019399 
Mc4rtm1Lowl Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001433 polyphagia PMID: 16269339 
Htr2ctm1Knk|Mc4rtm1Lowl Htr2ctm1Knk/Y,Mc4rtm1Lowl/Mc4rtm1Lowl
involves: 129S4/SvJae * C57BL/6
MGI:96281  MGI:99457  MP:0001433 polyphagia PMID: 19036977 
Mc4rtm1Dhu|Pomctm1Low Mc4rtm1Dhu/Mc4rtm1Dhu,Pomctm1Low/Pomctm1Low
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6
MGI:97742  MGI:99457  MP:0001433 polyphagia PMID: 12697680 
Mc4rtm1Dhu Mc4rtm1Dhu/Mc4rtm1Dhu
involves: 129S4/SvJae * C57BL/6J
MGI:99457  MP:0001921 reduced fertility PMID: 15596147 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Obesity due to melanocortin 4 receptor deficiency
Synonyms: Obesity [OMIM: 601665] [Disease Ontology: DOID:9970]
Disease Ontology: DOID:9970
OMIM: 601665
Orphanet: ORPHA71529
Comments: 
References:  10-11,37

References

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1. Adan RA, Szklarczyk AW, Oosterom J, Brakkee JH, Nijenhuis WA, Schaaper WM, Meloen RH, Gispen WH. (1999) Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat. Eur J Pharmacol, 378: 249-258. [PMID:10493100]

2. Al-Obeidi F, Hruby VJ, Castrucci AM, Hadley ME. (1989) Design of potent linear α-melanotropin 4-10 analogues modified in positions 5 and 10. J Med Chem., 32: 174-179. [PMID:2535874]

3. Bednarek MA, MacNeil T, Kalyani RN, Tang R, Van der Ploeg LH, Weinberg DH. (2001) Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. J. Med. Chem., 44 (22): 3665-72. [PMID:11606131]

4. Benoit SC, Schwartz MW, Lachey JL, Hagan MM, Rushing PA, Blake KA, Yagaloff KA, Kurylko G, Franco L, Danhoo W et al.. (2000) A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci., 20 (9): 3442-8. [PMID:10777807]

5. Böhm M, Eickelmann M, Li Z, Schneider SW, Oji V, Diederichs S, Barsh GS, Vogt A, Stieler K, Blume-Peytavi U et al.. (2005) Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of alpha-melanocyte-stimulating hormone in human dermal papilla cells. Endocrinology, 146 (11): 4635-46. [PMID:16081629]

6. Chaki S, Hirota S, Funakoshi T, Suzuki Y, Suetake S, Okubo T, Ishii T, Nakazato A, Okuyama S. (2003) 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. J. Pharmacol. Exp. Ther., 304 (2): 818-26. [PMID:12538838]

7. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem. Mol. Biol. Int., 38 (1): 73-80. [PMID:8932521]

8. Conde-Frieboes K, Thøgersen H, Lau JF, Sensfuss U, Hansen TK, Christensen L, Spetzler J, Olsen HB, Nilsson C, Raun K et al.. (2012) 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. J. Med. Chem., 55 (5): 1969-77. [PMID:22335602]

9. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature, 385 (6612): 165-8. [PMID:8990120]

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