MC<sub>4</sub> receptor | Melanocortin receptors | IUPHAR/BPS Guide to PHARMACOLOGY

MC4 receptor

Target id: 285

Nomenclature: MC4 receptor

Family: Melanocortin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for MC4 receptor in GtoImmuPdb

Gene and Protein Information
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 12,23
Mouse 7 184 18E1 Mc4r melanocortin 4 receptor
Rat 7 332 18p11 Mc4r melanocortin 4 receptor
Database Links
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
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat}
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 ligands (Human)
β-MSH (POMC, P01189) > α-MSH (POMC, P01189), ACTH (POMC, P01189) > γ-MSH (POMC, P01189)

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]NDP-MSH Hs Full agonist 8.4 – 8.9 pKd 18,29
pKd 8.4 – 8.9 (Kd 4x10-9 – 1.2x10-9 M) [18,29]
setmelanotide Hs Agonist 8.7 pKi 20
pKi 8.7 (Ki 2.1x10-9 M) [20]
afamelanotide Hs Full agonist 8.5 – 8.8 pKi 1,27,37
pKi 8.5 – 8.8 [1,27,37]
setmelanotide Rn Agonist 8.6 pKi 20
pKi 8.6 (Ki 2.7x10-9 M) [20]
MT-II Hs Full agonist 8.2 – 8.8 pKi 1-2,37
pKi 8.2 – 8.8 [1-2,37]
α-MSH {Sp: Human, Mouse, Rat} Hs Full agonist 7.4 – 8.0 pKi 1,37
pKi 7.4 – 8.0 [1,37]
ACTH {Sp: Human} Hs Agonist 6.2 pKi 30
pKi 6.2 (Ki 6.93x10-7 M) [30]
THIQ Hs Full agonist 8.9 pIC50 32
pIC50 8.9 (IC50 1.26x10-9 M) [32]
RY764 Hs Full agonist 8.1 pIC50 38
pIC50 8.1 [38]
View species-specific agonist tables
Agonist Comments
The relative potency of melanocortin peptides at the MC4 is β-MSH>α-MSH=ACTH>γ-MSH [21].

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 [19].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
MCL0129 Hs Antagonist 10.1 pKd 6
pKd 10.1 [6]
HS024 Hs Antagonist 9.5 pKd 15
pKd 9.5 [15]
[125I]SHU9119 Hs Antagonist 9.2 pKd 25
pKd 9.2 (Kd 7x10-10 M) [25]
HS014 Hs Antagonist 8.5 pKd 33
pKd 8.5 (Kd 3.16x10-9 M) [33]
agouti {Sp: Mouse} Mm Inverse agonist 7.3 pKd 16
pKd 7.3 [16]
SHU9119 Hs Antagonist 9.4 – 9.6 pKi 1,28
pKi 9.4 – 9.6 [1,28]
HS014 Hs Antagonist 8.5 pKi 31
pKi 8.5 (Ki 3.2x10-9 M) [31]
MBP10 Hs Antagonist 10.0 pIC50 3
pIC50 10.0 (IC50 1x10-10 M) [3]
agouti-related protein {Sp: Human} Hs Inverse agonist 9.3 pIC50 11
pIC50 9.3 [11]
PG-901 Hs Antagonist 8.1 pIC50 13
pIC50 8.1 [13]
View species-specific antagonist tables
Antagonist Comments
The pIC50 of full-length recombinant AGRP expressed in bacteria has been reported to be 7.06 [26].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  12,23
Secondary Transduction Mechanisms
Transducer Effector/Response
G protein (identity unknown) Other - See Comments
Comments:  Melanocortin activation of the MC4 mobilizes intracellular calcium via an incompletely understood pathway.
References:  22
Tissue Distribution
Dermal papilla cells.
Species:  Human
Technique:  RT-PCR and immunofluorescence,
References:  5
Pituitary gland.
Species:  Human
Technique:  PCR and hybridisation.
References:  7
Spinal cord: Intermediolateral cell column and dorsal horn.
Brain: Diencephalon neuroepithelia, telencephalon, lamina terminalis, spinal trigeminal nucleus.
Species:  Rat
Technique:  in situ hybridisation.
References:  24
Penis, spinal cord, hypothalamus, brainstem and pelvic ganglion.
Species:  Rat
Technique:  RT-PCR and RNase protection assay.
References:  35
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:  17
Expression Datasets

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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
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:  12,23
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:  22
Measurment of cAMP levels in cell lines transfected with the MC4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in cAMP.
References:  36
Physiological Functions
MC4 receptors are involved in the inhibition of feeding behaviour and the regulation of metabolism.
Species:  Mouse
Tissue:  In vivo
References:  8,14
The MC4 receptor is involved in sexual behaviour and male erectile function.
Species:  Mouse
Tissue:  In vivo.
References:  35
Physiological Consequences of Altering Gene Expression
MC4 receptor knock-out mice become obese, hyperphagic, hyperinsulinemic, and hyperglycemic.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
Phenotypes, Alleles and Disease Models 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
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:  9-10,34

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: 3665-3672. [PMID:11606131]

4. Benoit SC, Schwartz MW, Lachey JL, Hagan MM, Rushing PA, Blake KA, Yagaloff KA, Kurylko G, Franco L, Danhoo W, Seeley RJ. (2000) A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci., 20: 3442-3448. [PMID:10777807]

5. Bohm M, Eickelmann M, Li Z, Schneider SW, Oji V, Diederichs S, Barsh GS, Vogt A, Stieler K, Blume-Peytavi U, Luger TA. (2005) Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of {alpha}-melanocyte-stimulating hormone in human dermal papilla cells. Endocrinology,: -. [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-[2-methoxynaphthalen -1-yl) butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor. J. Pharmacol. Exp. Ther., 304: 818-826. [PMID:12538838]

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

8. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature, 385: 165-168. [PMID:8990120]

9. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med., 348: 1085-1095. [PMID:12646665]

10. Farooqi IS, O'Rahilly S. (2008) Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab, 4 (10): 569-77. [PMID:18779842]

11. Fong TM, Mao C, MacNeil T, Kalyani R, Smith T, Weinberg D, Tota MR, Van der Ploeg LH. (1997) ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors. Biochem. Biophys. Res. Commun., 237: 629-631. [PMID:9299416]

12. Gantz I, Konda Y, Tashiro T, Shimoto Y, Miwa H, Munzert G, Watson SJ, DelValle J, Yamada T. (1993) Molecular cloning of a novel melanocortin receptor. J. Biol. Chem., 268: 8246-8250. [PMID:8463333]

13. Grieco P, Lavecchia A, Cai M, Trivedi D, Weinberg D, MacNeil T, Van der Ploeg LH, Hruby VJ. (2002) Structure-activity studies of the melanocortin peptides: discovery of potent and selective affinity antagonists for the hMC3 and hMC4 receptors. J. Med. Chem., 45: 5287-5294. [PMID:12431055]

14. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 88: 131-141. [PMID:9019399]

15. Kask A, Mutulis F, Muceniece R, Pähkla R, Mutule I, Wikberg JE, Rägo L, Schiöth HB. (1998) Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology, 139: 5006-5014. [PMID:9832440]

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Tung M. Fong, Helgi Schiöth, Ira Gantz, Roger D. Cone, Sadaf Farooqi, Carrie Haskell-Luevano, Victor J. Hruby, Kathleen G. Mountjoy, Jeffrey B. Tatro, Jarl E. S. Wikberg.
Melanocortin receptors: MC4 receptor. Last modified on 20/02/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=285.