MC3R

Summary

MC3R (melanocortin 3 receptor, HGNC:6931) is a protein-coding gene on chromosome 20q13.2, encoding Melanocortin receptor 3 (P41968). G protein-coupled receptor for melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and corticotropin/ACTH, which are peptide products of the POMC precursor.

This gene encodes a G-protein-coupled receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone that is expressed in tissues other than the adrenal cortex and melanocytes. This gene maps to the same region as the locus for benign neonatal epilepsy. Mice deficient for this gene have increased fat mass despite decreased food intake, suggesting a role for this gene product in the regulation of energy homeostasis. Mutations in this gene are associated with a susceptibility to obesity in humans.

Source: NCBI Gene 4159 — RefSeq curated summary.

At a glance

• Gene–disease (curated): body mass index quantitative trait locus 9 (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 134 total
• Phenotypes (HPO): 1
• Druggable target: yes — 86 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_019888

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6931
Approved symbol	MC3R
Name	melanocortin 3 receptor
Location	20q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MC3
Ensembl gene	ENSG00000124089
Ensembl biotype	protein_coding
OMIM	155540
Entrez	4159

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000243911

RefSeq mRNA: 1 — MANE Select: NM_019888 NM_019888

CCDS: CCDS13449

Canonical transcript exons

ENST00000243911 — 1 exons

Exon	Start	End
ENSE00000845681	56248732	56249815

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 61.62.

Top tissues by expression

169 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	61.62	silver quality
deltoid	UBERON:0001476	60.35	silver quality
pleura	UBERON:0000977	58.76	silver quality
quadriceps femoris	UBERON:0001377	56.05	gold quality
vastus lateralis	UBERON:0001379	55.67	gold quality
cartilage tissue	UBERON:0002418	55.01	gold quality
epithelium of esophagus	UBERON:0001976	54.28	gold quality
squamous epithelium	UBERON:0006914	54.08	gold quality
dorsal plus ventral thalamus	UBERON:0001897	54.05	gold quality
nasal cavity epithelium	UBERON:0005384	54.04	gold quality
myocardium	UBERON:0002349	53.69	gold quality
trachea	UBERON:0003126	53.64	gold quality
male germ cell	CL:0000015	53.54	gold quality
epithelium of bronchus	UBERON:0002031	53.26	gold quality
thymus	UBERON:0002370	53.17	gold quality
layer of synovial tissue	UBERON:0007616	52.79	gold quality
epithelium of mammary gland	UBERON:0003244	52.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.84	gold quality
pancreatic ductal cell	CL:0002079	51.02	silver quality
epithelial cell of pancreas	CL:0000083	49.64	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
ileal mucosa	UBERON:0000331	48.52	silver quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. (PMID:11889220)
• An association between an insertion polymorphism was observed with fat mass, percent body fat, and total abdominal fat. (PMID:12142547)
• variaton in a Maori kindred with obesity and early onset type 2 diabetes (PMID:12161058)
• functional characterization of the I183N mutated MC3R compared with that of the wild-type MC3R after transfection in HEK293 cells (PMID:15276649)
• MC3R mutation might be genetic factor that confers susceptibility to obesity, likely due to haploinsufficiency. We identify a residue that is critical for activation of G protein-coupled receptors. (PMID:15292330)
• Outlining the ligand recognition sites in the melanocortin receptors. (PMID:15470082)
• melanocortin receptors (MC1R and MC3R) exist as constitutively pre-formed dimers (PMID:15582585)
• Single-nucleotide polymorphisms found in anorexia nervosa. (PMID:16314751)
• Our results suggest that TM3 and TM6 are important for NDP-MSH binding, while D121 in TM2 and D332 in TM7 are crucial for receptor activity and signaling.and thus provide molecular determinants of hMC3R responsible for ligand binding and receptor signals (PMID:16430209)
• in addition to its inverse agonistic activities, Agrp exhibits agonistic properties on the endocytosis pathway of melanocortin-3 and -4 receptors (PMID:17041250)
• SNPs of MC3R may regulate substrate oxidation and first-phase insulin secretion. (PMID:17192297)
• results suggest a gene-diet interaction between the MC3R C17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity (PMID:17413091)
• Further structure-activity studies of lactam derivatives of MT-II and SHU-9119 were made at MC3R. (PMID:17482720)
• MC3R mutations may not result in autosomal dominant forms of obesity but may contribute as a predisposing factor to childhood obesity. (PMID:17639020)
• highly conserved N/DPxxY motif, was critical for multiple aspects of the MC3R function, including cell surface expression, ligand binding, and signaling. (PMID:17964765)
• In the Maori kindred, the D20S32e polymorphism is significantly associated with insulin resistance but not with the metabolic syndrome. (PMID:18180070)
• in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity (PMID:18231126)
• there is a link between MC3R and cell growth pathways that may involve the alteration of AKT signaling pathway (PMID:18291523)
• unlikely that MC3R gene plays a major role in tuberculosis susceptibility in African populations (PMID:18420963)
• acidic residues in transmembrane (TM) domains 1 and 3 are important for ligand binding whereas the acidic residues in TMs 2 and 7 are important for both ligand binding and signaling (PMID:18614155)
• Mutations in MC4R are a significant cause of severe obesity but MC3R mutations are not associated with severe obesity in North American population. (PMID:19091795)
• Body mass index and fat mass were greater in those with double homozygosity for C17A + G241A (P = 0.001). After accounting for covariates…the number of minor C17A + G241A alleles was associated with significantly greater energy intake… (PMID:19656839)
• There is not sufficient evidence to support the contribution for common melanocortin-3 receptor variants in childhood obesity. However, our results are concordant for a role of melanocortin-3 receptor variants in some dimensions of eating behavior. (PMID:20144537)
• A role of the MC3R gene in the pathogenesis of obesity in a small subset of patients. (PMID:20539302)
• While MC3R is an important regulator of energy homeostasis, mutations in the MC3R gene remain controversially associated with human obesity pathogenesis.[Review] (PMID:20882712)
• data are consistent with the involvement of rs3746619 in weight regulation among obese individuals (PMID:20972733)
• in the populations studied functionally significant MC3R variants are associated with obesity (PMID:21047972)
• Polymorphisms in MC3R promoter and CTSZ 3’UTR are associated with tuberculosis susceptibility. (PMID:21368909)
• The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss. (PMID:21695122)
• We demonstrated that the MC3R polymorphisms have a protective effect on metabolic traits. (PMID:21920079)
• Carriers of the MC3R 6Lys-81Ile haplotype showed higher respiratory quotient and higher glucose oxidation compared with non-carriers after standardization for fat-free mass. (PMID:21983807)
• Extracellular cysteine residue C305, C311 and C313 are crucial for receptor expression and the transmembrane cysteine residue, C115 and 162 are important for ligand binding and signaling. (PMID:22079958)
• Interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. (PMID:22327910)
• The polymorphism T6K is not located in the coding region of the human MC3R and has no influence on translation initiation which makes an impact on body weight unlikely. (PMID:22433616)
• we provided detailed data of these novel human MC3R mutations leading to a better understanding of structure-function relationship of MC3R and the role of MC3R mutation in obesity (PMID:22884546)
• Overall, the total prevalence of rare MC3R variants was 1 % in Belgian obese children and adolescents compared to 1.02 % in lean controls. (PMID:23264184)
• while MC3R mutations are unlikely to result in an autosomal dominant form of monogenic obesity given lack of strong cosegregation in family studies, the studies provided evidence that MC3R can be one of the genes which contributes to increased adiposity [review] (PMID:23280863)
• Data suggest that specific amino acid residues (M247, R252, H254, K256, R257, A259) in 3rd intracellular loop (ICL3) of MC3R are important for ligand binding/signal transduction; studies used mutant, recombinant MC3R expressed in HEK293T cell line. (PMID:23323615)
• results suggest MC3R rs6127698 has no direct role in tuberculosis susceptibility. The possibility remains that this polymorphism is linked to an adjacent functional genetic variant, acting as a surrogate marker for disease risk (PMID:23497691)
• Suggest MC3R rs6127698 polymorphism is associated with pulmonary tuberculosis in a sample Iranian population. (PMID:23827504)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mc3r	ENSDARG00000021369
mus_musculus	Mc3r	ENSMUSG00000038537
rattus_norvegicus	Mc3r	ENSRNOG00000004451

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Melanocortin receptor 3 — P41968 (reviewed: P41968)

All UniProt accessions (1): P41968

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and corticotropin/ACTH, which are peptide products of the POMC precursor. Upon activation, couples to G(s) protein, stimulating adenylate cyclase and the cAMP-dependent signaling pathway, which contributes to the regulation of energy homeostasis. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain. Binding of the Agouti-related protein/AGPR antagonist precludes alpha-MSH-induced signaling, blocking cAMP production.

Subcellular location. Cell membrane.

Tissue specificity. Brain, placental, and gut tissues.

Polymorphism. Genetic variations in MC3R define the body mass index quantitative trait locus 9 (BMIQ9) [MIM:602025]. Variance in body mass index is a susceptibility factor for obesity.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_063941* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001671	Melcrt_ACTH_rcpt	Family
IPR001908	MC3-5R	Family
IPR002122	Mcort_3_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (60 total): mutagenesis site 18, helix 10, topological domain 8, transmembrane region 7, binding site 3, glycosylation site 3, sequence variant 3, strand 3, disulfide bond 2, chain 1, lipid moiety-binding region 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9K3F	ELECTRON MICROSCOPY	2.75
8IOC	ELECTRON MICROSCOPY	2.86
8W8W	ELECTRON MICROSCOPY	2.9
8W8X	ELECTRON MICROSCOPY	2.9
8W8Y	ELECTRON MICROSCOPY	2.9
8KIG	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41968-F1	84.32	0.62

Antibody-complex structures (SAbDab): 5 — 8IOC, 8W8W, 8W8X, 8W8Y, 9K3F

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 94; 117; 121

Post-translational modifications (1): 315

Disulfide bonds (2): 35–276, 268–274

Glycosylation sites (3): 2, 16, 28

Mutagenesis-validated functional residues (18):

Position	Phenotype
45	over 100-fold decrease in gamma-msh potency.
94	loss of gamma-msh potency.
94	decreased gamma-msh-induced camp accumulation.
98	10 to 100-fold decrease in gamma-msh potency.
113	2 to 10 fold decrease in gamma-msh potency.
117	10 to 100-fold decrease in gamma-msh potency.
117	decreased gamma-msh-induced camp accumulation.
121	10 to 100-fold decrease in gamma-msh potency.
121	loss of gamma-msh-induced camp accumulation.
180	10 to 100-fold decrease in gamma-msh potency.
189	2 to 10 fold decrease in gamma-msh potency.
192	2 to 10 fold decrease in gamma-msh potency.
258	10 to 100-fold decrease in gamma-msh potency.
261	10 to 100-fold decrease in gamma-msh potency.
265	3-fold decrease in gamma-msh potency.
265	18-fold decrease in gamma-msh potency.
265	4-fold decrease in gamma-msh potency.
281	2 to 10 fold decrease in gamma-msh potency.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 97 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_BEHAVIOR, GOBP_REGULATION_OF_FEEDING_BEHAVIOR, GOBP_REGULATION_OF_HEART_RATE, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SODIUM_ION_HOMEOSTASIS, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_RHYTHMIC_BEHAVIOR

GO Biological Process (14): regulation of heart rate (GO:0002027), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), regulation of blood pressure (GO:0008217), circadian regulation of gene expression (GO:0032922), homoiothermy (GO:0042309), locomotor rhythm (GO:0045475), sodium ion homeostasis (GO:0055078), regulation of feeding behavior (GO:0060259), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), rhythmic process (GO:0048511)

GO Molecular Function (6): melanocortin receptor activity (GO:0004977), melanocyte-stimulating hormone receptor activity (GO:0004980), peptide hormone binding (GO:0017046), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
MITF-M-regulated melanocyte development	1
Signal Transduction	1
GPCR ligand binding	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
regulation of biological quality	2
hormone binding	2
cellular anatomical structure	2
regulation of heart contraction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
blood circulation	1
circadian rhythm	1
regulation of gene expression	1
temperature homeostasis	1
locomotory behavior	1
circadian behavior	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
feeding behavior	1
regulation of behavior	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activity	1
biological_process	1
G protein-coupled peptide receptor activity	1
melanocortin receptor activity	1
peptide binding	1
transmembrane signaling receptor activity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MC3R	POMC	P01189	998
MC3R	AGRP	O00253	996
MC3R	ATP7A	Q04656	896
MC3R	CTSZ	Q9UBR2	850
MC3R	GHSR	Q92847	849
MC3R	GHRL	Q9UBU3	838
MC3R	NPY	P01303	828
MC3R	LEP	P41159	826
MC3R	MRAP2	Q96G30	775
MC3R	ASIP	P42127	757
MC3R	PYY	P10082	753
MC3R	PCSK1	P29120	748
MC3R	FTO	Q9C0B1	701
MC3R	SH2B1	Q9NRF2	693
MC3R	MT2A	P02795	684

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MRAP	MC3R	psi-mi:“MI:0915”(physical association)	0.400
MRAP2	MC3R	psi-mi:“MI:0915”(physical association)	0.400
CFTR	MC3R	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): MC3R (Proximity Label-MS), MC3R (Reconstituted Complex), MC3R (PCA)

ESM2 similar proteins: B0V1P1, O19037, O77616, O97504, P32244, P32245, P33032, P33033, P34974, P35345, P41149, P41968, P41983, P55167, P56442, P56450, P56451, P70115, P70596, P79166, Q01718, Q01727, Q0Z8I9, Q29154, Q64326, Q6A155, Q80SS9, Q80SZ5, Q864F7, Q864F8, Q864G9, Q864H1, Q864H2, Q864H3, Q864H4, Q864H5, Q864I1, Q864I2, Q864I3, Q864K7

Diamond homologs: B0V1P1, O19037, O77616, O97504, P32244, P32245, P33032, P33033, P34974, P35345, P41149, P41968, P41983, P47798, P55167, P56442, P56443, P56444, P56445, P56446, P56447, P56448, P56450, P56451, P70115, P70596, P79166, Q01718, Q01726, Q01727, Q0Q460, Q0Z8I9, Q29154, Q64326, Q6A155, Q80SS9, Q80SZ5, Q864F4, Q864F5, Q864F6

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
AGRP	“down-regulates activity”	MC3R	binding
MC3R	“up-regulates activity”	GNAS
MC3R	“up-regulates activity”	GNAL	binding
MC3R	“up-regulates activity”	GNAI3	binding
MC3R	“up-regulates activity”	GNAO1	binding
MC3R	“up-regulates activity”	GNAZ	binding
MC3R	“up-regulates activity”	GNAQ	binding
MC3R	“up-regulates activity”	GNA14	binding
MC3R	“up-regulates activity”	GNA15	binding
MC3R	“up-regulates activity”	GNA12	binding
“MSH release-inhibiting hormone”	“up-regulates activity”	MC3R	“chemical activation”
MC3R	“up-regulates activity”	GNAS	binding
ASIP	“down-regulates activity”	MC3R	binding
POMC	“up-regulates activity”	MC3R	binding
Corticotropin	“up-regulates activity”	MC3R	binding
AGRP	down-regulates	MC3R	binding
MRAP	“down-regulates activity”	MC3R	binding
MRAP2	“down-regulates activity”	MC3R	binding
“Melanotan II”	“up-regulates activity”	MC3R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

134 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	37
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

96 predictions. Top by Δscore:

Variant	Effect	Δscore
20:56249561:G:GT	donor_gain	0.7200
20:56249588:G:GT	donor_gain	0.6800
20:56249557:G:GT	donor_gain	0.6400
20:56249496:TC:T	donor_gain	0.6100
20:56249564:G:T	donor_gain	0.5800
20:56249427:T:G	acceptor_gain	0.5500
20:56249532:T:TA	donor_gain	0.5200
20:56249439:T:TA	acceptor_gain	0.5100
20:56249564:G:GT	donor_gain	0.5100
20:56249494:C:G	acceptor_gain	0.5000
20:56249533:G:GA	donor_gain	0.5000
20:56249590:C:T	donor_gain	0.4800
20:56249452:G:A	acceptor_gain	0.4700
20:56249472:T:G	acceptor_gain	0.4700
20:56249266:CAG:C	donor_loss	0.4500
20:56249269:GTAC:G	donor_loss	0.4500
20:56249270:T:A	donor_loss	0.4500
20:56249450:ATG:A	acceptor_gain	0.4500
20:56249486:C:CA	acceptor_gain	0.4500
20:56249438:AT:A	acceptor_gain	0.4300
20:56249484:C:CA	acceptor_gain	0.4300
20:56249451:T:TA	acceptor_gain	0.4200
20:56249628:T:TA	acceptor_gain	0.4200
20:56249562:G:T	donor_gain	0.4100
20:56249588:G:T	donor_gain	0.4100
20:56249359:C:CA	acceptor_gain	0.4000
20:56249407:C:A	donor_gain	0.4000
20:56249625:ACCT:A	acceptor_gain	0.4000
20:56249439:T:G	acceptor_gain	0.3900
20:56249450:AT:A	acceptor_gain	0.3800

AlphaMissense

2159 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:56249078:A:C	S79R	0.999
20:56249080:C:A	S79R	0.999
20:56249080:C:G	S79R	0.999
20:56249105:A:C	S88R	0.999
20:56249107:T:A	S88R	0.999
20:56249107:T:G	S88R	0.999
20:56248997:A:C	S52R	0.998
20:56248999:T:A	S52R	0.998
20:56248999:T:G	S52R	0.998
20:56249095:C:A	D84E	0.995
20:56249095:C:G	D84E	0.995
20:56249348:T:A	W169R	0.995
20:56249348:T:C	W169R	0.995
20:56249606:T:A	W255R	0.995
20:56249606:T:C	W255R	0.995
20:56249613:C:G	P257R	0.995
20:56249730:C:A	P296Q	0.995
20:56249011:C:A	N56K	0.994
20:56249011:C:G	N56K	0.994
20:56249613:C:A	P257H	0.994
20:56249010:A:C	N56T	0.993
20:56249019:T:A	V59D	0.993
20:56249093:G:C	D84H	0.993
20:56249094:A:C	D84A	0.993
20:56249245:C:A	N134K	0.993
20:56249245:C:G	N134K	0.993
20:56249588:G:C	G249R	0.993
20:56249594:T:C	F251L	0.993
20:56249596:C:A	F251L	0.993
20:56249596:C:G	F251L	0.993

dbSNP variants (sampled 300 via entrez): RS1000156919 (20:56248880 A>G,T), RS1000172340 (20:56248740 T>C), RS1001856286 (20:56247162 G>A,T), RS1003533870 (20:56248427 G>T), RS1004386634 (20:56247098 C>A), RS1004737036 (20:56248194 A>G), RS1005603165 (20:56248126 C>T), RS1006394773 (20:56249601 T>A), RS1008793152 (20:56247737 C>T), RS1008988795 (20:56247996 G>A,T), RS1009523658 (20:56248941 C>T), RS1010576767 (20:56247460 C>T), RS1010939849 (20:56250297 G>A,C,T), RS1010983722 (20:56247713 C>T), RS1012345545 (20:56246800 ATGTGCGTGTGTGTG>A)

Disease associations

OMIM: gene MIM:155540 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
body mass index quantitative trait locus 9	Limited	Unknown

Mondo (2): obesity disorder (MONDO:0011122), (MONDO:0044272)

Orphanet (3): NON RARE IN EUROPE: Obesity due to MC3R deficiency (Orphanet:217031), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001513	Obesity

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005950_8	Body mass index x sex x age interaction (4df test)	2.000000e-06
GCST005951_199	Body mass index	7.000000e-06
GCST005953_2	Body mass index (age <50)	9.000000e-08
GCST009391_26	Metabolite levels	2.000000e-06
GCST010988_330	Adult body size	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010350	cholesteryl ester 22:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111323 (SELECTIVITY GROUP), CHEMBL4523974 (SELECTIVITY GROUP), CHEMBL4644 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

86 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 686,976 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL113	CAFFEINE	4	200,591
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1198857	VILANTEROL	4	2,552
CHEMBL1200661	UNOPROSTONE ISOPROPYL	4	2,396
CHEMBL1201284	CINACALCET	4	5,917
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201309	NAFARELIN	4
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1305	ANTAZOLINE	4	9,182
CHEMBL13280	FLUNITRAZEPAM	4	11,549
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1373	MODAFINIL	4	14,293
CHEMBL1378	THIETHYLPERAZINE	4
CHEMBL1401	NITAZOXANIDE	4
CHEMBL1423	PIMOZIDE	4
CHEMBL1491	AMLODIPINE	4
CHEMBL1492500	DOTHIEPIN	4
CHEMBL1617	RIFAXIMIN	4
CHEMBL1626	CLEMASTINE	4
CHEMBL1651990	FENTICONAZOLE	4
CHEMBL17157	TERFENADINE	4
CHEMBL178	DAUNORUBICIN	4

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Melanocortin receptors

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
[125I]NDP-MSH	Full agonist	9.7	pKd
PG-901	Antagonist	9.7	pIC50
SHU9119	Antagonist	9.1	pKi
afamelanotide	Full agonist	8.9	pKi
γ-MSH	Full agonist	8.5	pKd
α-MSH	Full agonist	8.4	pKi
MT-II	Full agonist	8.3	pKi
HS024	Antagonist	8.3	pKd
[D-Trp8]γ-MSH	Full agonist	8.2	pIC50
setmelanotide	Agonist	8.0	pKi
agouti-related protein	Inverse agonist	7.7	pIC50
HS014	Antagonist	7.3	pKd
bremelanotide	Agonist	7.28	pKi
ACTH	Agonist	7.06	pKi
agouti	Inverse agonist	6.7	pIC50
PG-106	Antagonist	6.7	pIC50
AP1189	Biased agonist	6.44	pKd

Binding affinities (BindingDB)

35 measured of 38 human assays (38 total across all organisms); most potent 35 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CAS_75921-69-6	KI	0.224 nM
alpha-MSH, [Nle4, D-Phe7]	KI	0.224 nM
desacetyl-alpha-MSH	KI	3.68 nM
Gamma1-MSH	KI	7.06 nM
alpha-MSH, [Nle4]	KI	9.85 nM
Gamma3-MSH	KI	10.9 nM
beta MSH, human	KI	13.4 nM
CAS_72711-43-4	KI	17.7 nM
CAS_10466-28-1	KI	20.7 nM
ACTH	KI	86.9 nM
ACTH-(1-10)	KI	145 nM
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2-fluoro-4-methylphenyl)propanoic acid	EC50	180 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2,6-difluoro-4-methylphenyl)propanoic acid	EC50	330 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-4-(2,4-difluorophenyl)-1-(1-methyl-6-oxopyridazin-3-yl)pyrrolidine-3-carbonyl]-3-[2-(dimethylamino)ethyl]piperazin-1-yl]-3-naphthalen-2-ylpropanoic acid	EC50	580 nM	US-10301286: Piperazine derivative
(2S,3S)-2-[(3S)-4-[(3S,4R)-4-(4-chloro-2-fluorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(4-methylphenyl)butanoic acid	EC50	680 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2,4,6-trimethylphenyl)propanoic acid	EC50	780 nM	US-10301286: Piperazine derivative
NSC_123787	KI	784 nM
(2S)-2-[(3S)-4-[(3S,4R)-4-(4-chloro-2-fluorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2-fluoro-4,6-dimethylphenyl)propanoic acid	EC50	880 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonyl]-3-propylpiperazin-1-yl]-3-naphthalen-2-ylpropanoic acid	EC50	910 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-4-(4-chloro-2-fluorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2-fluoro-4-methylphenyl)propanoic acid	EC50	920 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-4-(2,4-difluorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2-fluoro-4-methylphenyl)-2-methylpropanoic acid	EC50	1000 nM	US-10301286: Piperazine derivative
(E)-3-(4-chlorophenyl)-N-[[(3R,5R)-1-(2,2-diphenylethyl)-2-oxo-3-(2-piperidin-1-ylethyl)-1,4-diazepan-5-yl]methyl]prop-2-enamide	IC50	1500 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor
N-[[(3R,5R)-3-[3-(diaminomethylideneamino)propyl]-1-(2,2-diphenylethyl)-2-oxo-1,4-diazepan-5-yl]methyl]naphthalene-2-carboxamide	IC50	1750 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor
(2S)-2-[(3S)-4-[(3S,4R)-4-(4-chloro-2-fluorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(4-cyclopropyl-2-fluorophenyl)propanoic acid	EC50	1800 nM	US-10301286: Piperazine derivative
(E)-3-(4-chlorophenyl)-N-[[(3R,5R)-1-(2-ethylbutyl)-2-oxo-3-(2-piperidin-1-ylethyl)-1,4-diazepan-5-yl]methyl]prop-2-enamide	IC50	1830 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor
N-[[(3R,5R)-1-(2,2-diphenylethyl)-2-oxo-3-(3-piperidin-1-ylpropyl)-1,4-diazepan-5-yl]methyl]naphthalene-2-carboxamide	IC50	2240 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-cyclohexylpropanoic acid	EC50	2400 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2-fluoro-4-methoxyphenyl)propanoic acid	EC50	2900 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(4-methylphenyl)propanoic acid	EC50	3700 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2,3-dihydro-1H-inden-5-yl)propanoic acid	EC50	4200 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-[4-(trifluoromethyl)phenyl]propanoic acid	EC50	5000 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-1-tert-butyl-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-[4-(difluoromethoxy)phenyl]propanoic acid	EC50	5300 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[(3S,4R)-4-(2,4-difluorophenyl)-1-(1-hydroxy-2-methylpropan-2-yl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2,3-dihydro-1H-inden-5-yl)propanoic acid	EC50	10000 nM	US-10301286: Piperazine derivative
(2S)-2-[(3S)-4-[1-tert-butyl-4-(4-cyano-2-fluorophenyl)pyrrolidine-3-carbonyl]-3-methylpiperazin-1-yl]-3-(2,3-dihydro-1H-inden-5-yl)propanoic acid	EC50	11000 nM	US-10301286: Piperazine derivative
N-adamantan-2-yl-N-(4-amino-butyl)-2-[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-acetamide	KI	19000 nM

ChEMBL bioactivities

1461 potent at pChembl≥5 of 1748 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.66	Ki	0.02188	nM	CHEMBL4777048
10.66	Ki	0.022	nM	CHEMBL4777048
10.60	Kd	0.02512	nM	CHEMBL253364
10.51	Ki	0.0309	nM	CHEMBL4794121
10.51	Ki	0.031	nM	CHEMBL4794121
10.49	Ki	0.03236	nM	CHEMBL4798971
10.49	Ki	0.032	nM	CHEMBL4798971
10.21	EC50	0.06166	nM	MELATONAN
10.20	EC50	0.063	nM	CHEMBL413212
9.98	EC50	0.1047	nM	CHEMBL5185775
9.97	EC50	0.1072	nM	CHEMBL5185945
9.96	Ki	0.11	nM	CHEMBL414718
9.89	Ki	0.1288	nM	CHEMBL3422426
9.89	Ki	0.129	nM	CHEMBL3422426
9.89	EC50	0.13	nM	AFAMELANOTIDE
9.88	EC50	0.132	nM	AFAMELANOTIDE
9.87	Ki	0.1349	nM	CHEMBL4794168
9.87	Ki	0.135	nM	CHEMBL4794168
9.82	EC50	0.1514	nM	SETMELANOTIDE
9.80	Kd	0.1585	nM	CHEMBL398665
9.80	EC50	0.1585	nM	CHEMBL5172738
9.74	EC50	0.182	nM	CHEMBL5191309
9.72	IC50	0.19	nM	CHEMBL1161322
9.72	EC50	0.191	nM	CHEMBL428615
9.70	Ki	0.2	nM	CHEMBL2370968
9.69	EC50	0.2042	nM	MELATONAN
9.68	IC50	0.21	nM	CHEMBL1161313
9.64	Ki	0.23	nM	CHEMBL442504
9.64	Ki	0.23	nM	CHEMBL415165
9.64	EC50	0.2291	nM	CHEMBL5195641
9.64	IC50	0.23	nM	CHEMBL2096742
9.62	EC50	0.24	nM	MELATONAN
9.62	EC50	0.24	nM	AFAMELANOTIDE
9.57	EC50	0.27	nM	MELATONAN
9.56	EC50	0.2754	nM	CHEMBL5178164
9.52	EC50	0.3	nM	AFAMELANOTIDE
9.52	EC50	0.302	nM	CHEMBL5170533
9.51	EC50	0.309	nM	CHEMBL5175487
9.48	EC50	0.33	nM	CHEMBL405282
9.48	Ki	0.3311	nM	CHEMBL4788071
9.48	Ki	0.33	nM	CHEMBL4788071
9.48	EC50	0.3311	nM	CHEMBL5203986
9.46	EC50	0.3467	nM	CHEMBL5192329
9.45	Ki	0.3548	nM	CHEMBL4794990
9.45	Ki	0.352	nM	CHEMBL4794990
9.44	EC50	0.36	nM	AFAMELANOTIDE
9.44	EC50	0.36	nM	CHEMBL413912
9.42	Ki	0.3802	nM	CHEMBL4791788
9.42	Ki	0.378	nM	CHEMBL4791788
9.41	Ki	0.389	nM	CHEMBL4793821

PubChem BioAssay actives

1427 with measured affinity, of 4072 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-3-[(6-chloro-1H-indol-3-yl)methyl]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	<0.0001	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-3-[(7-chloro-1H-indol-3-yl)methyl]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	<0.0001	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-3-[(6-fluoro-1H-indol-3-yl)methyl]-12-(1H-imidazol-5-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	<0.0001	uM
(2S,5S,8S,11R,14S,23S)-23-amino-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-5-(naphthalen-2-ylmethyl)-3,6,9,12,20,24-hexaoxo-1,4,7,10,13,19-hexazacyclotetracosane-14-carboxamide	312481: Antagonist activity at human MC3 receptor expressed in HEK293 cells assessed as inhibition of MT2 induced intracellular cAMP accumulation	kd	<0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	108779: Effective concentration required for the biological activity against human Melanocortin 3 receptor	ec50	0.0001	uM
(6S,9S,12S,15R,18S,21S)-21-[[(2S)-2-acetamidohexanoyl]amino]-12-[3-(diaminomethylideneamino)propyl]-18-(1H-imidazol-5-ylmethyl)-9-(1H-indol-3-ylmethyl)-15-(naphthalen-2-ylmethyl)-8,11,14,17,20-pentaoxo-1,7,10,13,16,19,24,25-octazabicyclo[21.2.1]hexacosa-23(26),24-diene-6-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0001	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-53-[2-[2-(2-aminoethoxy)ethoxy]ethylcarbamoyloxymethyl]-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,59-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,61,62-heptadecazapentacyclo[26.17.15.248,58.049,57.052,54]dohexaconta-48(62),49(57),58(61)-trien-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0001	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S,49Z)-49-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethylamino]-2-oxoethoxy]imino-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,51-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazabicyclo[26.17.7]dopentacontan-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0001	uM
(3R,6S,9R,12S,15S,23R)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-[(4-chlorophenyl)methyl]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	108781: Evaluated for agonist activity at cloned Melanocortin 3 receptor	ec50	0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[(2S)-2-[[(2S)-6-amino-1-[[(2S)-1-amino-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	239512: Inhibition of [125I]-NDP-alpha-MSH binding to melanocortin-3 receptor expressed in HEK293 cells	ki	0.0001	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1812558: Agonist activity at human melanocortin receptor 3 expressed in human T-REx-293 cells assessed as stimulation of intracellular cAMP accumulation incubated for 45 mins by LANCE cAMP assay	ec50	0.0001	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0001	uM
Setmelanotide	1812558: Agonist activity at human melanocortin receptor 3 expressed in human T-REx-293 cells assessed as stimulation of intracellular cAMP accumulation incubated for 45 mins by LANCE cAMP assay	ec50	0.0002	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-50-hex-5-ynyl-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,49,51-heptadecaoxo-47,53-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,50-hexadecazatricyclo[26.17.9.048,52]tetrapentacont-48(52)-en-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0002	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,48-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazabicyclo[26.17.4]nonatetracontan-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0002	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,52-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,49,50,54,55-nonadecazatricyclo[26.17.8.248,51]pentapentaconta-48(55),49,51(54)-trien-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0002	uM
(3R,6S,9R,12S,15S,23R)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-9-[(4-fluorophenyl)methyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	108781: Evaluated for agonist activity at cloned Melanocortin 3 receptor	ec50	0.0002	uM
(3R,6S,9S,12S,15S,23R)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	223526: Binding affinity against human melanocortin receptor 3 (hMC3R) (concentration of the peptide at 50% specific binding)	ki	0.0002	uM
(3R,11S,14S,17R,20S,23R)-3-[[(2R)-2-acetamidohexanoyl]amino]-17-[3-(diaminomethylideneamino)propyl]-22-hydroxy-14-(1H-indol-3-ylmethyl)-20-(naphthalen-2-ylmethyl)-2,5,13,16,19-pentaoxo-1,6,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	109606: Binding affinity for human Melanocortin-3 receptor	ic50	0.0002	uM
(3R,11S,14S,17R,20S,23R)-3-[[(2R)-2-acetamidohexanoyl]amino]-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-20-(naphthalen-2-ylmethyl)-2,5,13,16,19,22-hexaoxo-1,6,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	109606: Binding affinity for human Melanocortin-3 receptor	ic50	0.0002	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-(carboxymethylamino)-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-3-carboxy-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-oxopentanoic acid	239512: Inhibition of [125I]-NDP-alpha-MSH binding to melanocortin-3 receptor expressed in HEK293 cells	ki	0.0002	uM
(7S,10R,13S,16S,19S)-13-[3-(diaminomethylideneamino)propyl]-16-(1H-indol-3-ylmethyl)-10-(naphthalen-2-ylmethyl)-2,8,11,14,17,28-hexaoxo-3,9,12,15,18,24-hexazatricyclo[27.4.0.03,7]tritriaconta-1(33),29,31-triene-19-carboxamide	312481: Antagonist activity at human MC3 receptor expressed in HEK293 cells assessed as inhibition of MT2 induced intracellular cAMP accumulation	kd	0.0002	uM
(3S,6S,9R,12S,15R,23S)-15-[[(2R)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	109606: Binding affinity for human Melanocortin-3 receptor	ic50	0.0002	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-1-[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	108799: Binding affinity against human Melanocortin 3 receptor by gamma-MCH displacement.	ki	0.0002	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-3-[(7-fluoro-1H-indol-3-yl)methyl]-12-(1H-imidazol-5-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0003	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,51-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazabicyclo[26.17.7]dopentacontan-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0003	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-49,50,54,55-tetrafluoro-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,52-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazatricyclo[26.17.8.248,51]pentapentaconta-48,50,54-trien-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0003	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,55-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazatricyclo[26.17.11.149,53]heptapentaconta-49,51,53(57)-trien-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0003	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,56-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazatricyclo[26.17.12.049,54]heptapentaconta-49,51,53-trien-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0003	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,54-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazatricyclo[26.17.10.249,52]heptapentaconta-49,51,56-trien-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0003	uM
(3S)-3-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]acetyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-[[(2S)-1-[[(2S)-1-(carboxymethylamino)-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	108780: Effective concentration required for intracellular cAMP accumulation against Melanocortin 3 receptor	ec50	0.0003	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-9-[(4-phenylphenyl)methyl]-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0004	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-3-[(5-fluoro-1H-indol-3-yl)methyl]-12-(1H-imidazol-5-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0004	uM
(6S,9S,12S,15R,18S,21S)-21-[[(2S)-2-acetamidohexanoyl]amino]-12-[3-(diaminomethylideneamino)propyl]-18-(1H-imidazol-5-ylmethyl)-9-(1H-indol-3-ylmethyl)-15-(naphthalen-2-ylmethyl)-8,11,14,17,20-pentaoxo-1,7,10,13,16,19,25,26-octazabicyclo[21.3.0]hexacosa-23,25-diene-6-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0004	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,49,51-heptadecaoxo-47,53-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,50-hexadecazatricyclo[26.17.9.048,52]tetrapentacont-48(52)-en-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0004	uM
(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	246074: Agonistic activity against human Melanocortin 3 receptor	ec50	0.0004	uM
(2S)-2-[(3S)-4-[(2R)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]-3-[3-(diaminomethylideneamino)propyl]-2-oxopiperazin-1-yl]-N-methyl-3-naphthalen-2-ylpropanamide	270600: Agonist activity at human MC3R	ec50	0.0004	uM
(2S)-2-acetamido-N-[(2R)-1-[(2S)-2-[3-(diaminomethylideneamino)propyl]-4-[(2S)-1-(methylamino)-3-naphthalen-2-yl-1-oxopropan-2-yl]-3-oxopiperazin-1-yl]-3-(4-fluorophenyl)-1-oxopropan-2-yl]pentanediamide	270600: Agonist activity at human MC3R	ec50	0.0005	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-53-(2-aminoethylcarbamoyloxymethyl)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,59-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,61,62-heptadecazapentacyclo[26.17.15.248,58.049,57.052,54]dohexaconta-48(62),49(57),58(61)-trien-7-yl]acetic acid	1852335: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay	ki	0.0006	uM
3-[2-[2-[2-[2-[[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-7-(carboxymethyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxo-47,59-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,61,62-heptadecazapentacyclo[26.17.15.248,58.049,57.052,54]dohexaconta-48(62),49(57),58(61)-trien-53-yl]methoxycarbonylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0006	uM
(3R,11S,14S,17R,20S,23S)-3-[[(2R)-2-acetamidohexanoyl]amino]-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-20-(naphthalen-2-ylmethyl)-2,5,13,16,19,22-hexaoxo-1,6,12,15,18,21-hexazatricyclo[21.8.0.025,30]hentriaconta-25,27,29-triene-11-carboxamide	109612: pA2 value for human Melanocortin-3 receptor	kd	0.0006	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	108779: Effective concentration required for the biological activity against human Melanocortin 3 receptor	ec50	0.0007	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-3-[(5-chloro-1H-indol-3-yl)methyl]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1743779: Displacement of [125I]-[NIe,DPhe7]-alpha-MSH from human MC3R expressed in HEK293 cell membranes incubated for 120 mins	ki	0.0007	uM
2-[(1R,4S,7S,10S,13S,16S,19S,25S,28R,31S,34S,37S,40S,43S)-16,40-dibenzyl-25-butyl-4,13,31,37-tetrakis(3-carbamimidamidopropyl)-19,43-bis(1H-imidazol-5-ylmethyl)-10,34-bis(1H-indol-3-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,49-hexadecaoxo-47,51-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41,44-pentadecazabicyclo[26.17.7]dopentacontan-7-yl]acetic acid	1852338: Agonist activity at human MC3R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0007	uM
(2S)-2-acetamido-N-[(2R)-1-[[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide	1480173: Agonist activity at human MC3R expressed in low doxycyclin-treated HEK293 cell membranes assessed as increase in cAMP production after 45 mins by HTRF method	ec50	0.0007	uM
3-[(4R,7S,10R,13R,16R,19S,22R)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-13-benzyl-4-carbamoyl-10-[3-(diaminomethylideneamino)propyl]-16-(1H-imidazol-5-ylmethyl)-7-(1H-indol-3-ylmethyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexazacyclotricos-19-yl]propanoic acid	246161: Agonist activity at human Melanocortin-3 receptor as peptide required for 50% maximal cAMP release	ec50	0.0007	uM
Bremelanotide	1812558: Agonist activity at human melanocortin receptor 3 expressed in human T-REx-293 cells assessed as stimulation of intracellular cAMP accumulation incubated for 45 mins by LANCE cAMP assay	ec50	0.0007	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2R)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-1,7-dimethyl-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1239141: Antagonist activity at human MC3 receptor expressed in HEK293 cells assessed as inhibition of MT-II-induced intracellular cAMP accumulation using [3H]-cAMP by luminescence counting	kd	0.0008	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]pentanoic acid	1476997: Agonist activity at human MC3R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins	ec50	0.0008	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	108799: Binding affinity against human Melanocortin 3 receptor by gamma-MCH displacement.	ki	0.0008	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
hydroxyhydroquinone	increases expression	1
sodium arsenite	increases expression	1
indole	affects binding	1
naphthalene	affects binding	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Folic Acid	decreases expression	1
Phthalic Acids	increases methylation	1
Vitallium	decreases expression	1

ChEMBL screening assays

313 unique, capped per target: 170 binding, 139 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL826750	Binding	Ratio of EC50 of Melanocortin 4 receptor to that of Melanocortin 3 receptor	End-capping of the modified melanocortin tetrapeptide (p-Cl)Phe-D-Phe-Arg-Trp-NH2 as a route to hMC4R agonists. — Bioorg Med Chem Lett
CHEMBL1027400	Functional	Agonist activity at human MC3R expressed in HEK293 cells assessed as effect on CRE-driven luminescence by luciferase reporter gene assay	Discovery of orally bioavailable 1,3,4-trisubstituted 2-oxopiperazine-based melanocortin-4 receptor agonists as potential antiobesity agents. — J Med Chem
CHEMBL4032179	ADMET	Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells after 40 mins by gamma counting method	Design of MC1R Selective γ-MSH Analogues with Canonical Amino Acids Leads to Potency and Pigmentation. — J Med Chem

Cellosaurus cell lines

8 cell lines: 3 spontaneously immortalized cell line, 3 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0T4	ACTOne MC3R	Transformed cell line	Female
CVCL_H371	293/MC3/CRE-Luc	Transformed cell line	Female
CVCL_H460	CHO-K1/MC3/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV46	cAMP Hunter CHO-K1 MC3R Gs	Spontaneously immortalized cell line	Female
CVCL_LA68	PathHunter U2OS MC3R beta-arrestin	Cancer cell line	Female
CVCL_LA69	PathHunter U2OS MC3R Total GPCR Internalization	Cancer cell line	Female
CVCL_YK54	U2OS MC3R cAMP-Nomad	Cancer cell line	Female
CVCL_ZK73	GeneBLAzer MC3R-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	PHASE4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	PHASE4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients