MC5R

Summary

MC5R (melanocortin 5 receptor, HGNC:6933) is a protein-coding gene on chromosome 18p11.21, encoding Melanocortin receptor 5 (P33032). 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 member of the seven-pass transmembrane G protein-coupled melanocortin receptor protein family that stimulate cAMP signal transduction. The encoded protein is a receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone and is suggested to play a role in sebum generation.

Source: NCBI Gene 4161 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 57 total — 1 pathogenic
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6933
Approved symbol	MC5R
Name	melanocortin 5 receptor
Location	18p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176136
Ensembl biotype	protein_coding
OMIM	600042
Entrez	4161

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000324750, ENST00000589410

RefSeq mRNA: 1 — MANE Select: NM_005913 NM_005913

CCDS: CCDS11868

Canonical transcript exons

ENST00000589410 — 2 exons

Exon	Start	End
ENSE00002865688	13825727	13827323
ENSE00002868397	13824149	13824274

Expression profiles

Bgee: expression breadth broad, 47 present calls, max score 86.49.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.43	gold quality
amniotic fluid	UBERON:0000173	61.70	gold quality
epithelium of nasopharynx	UBERON:0001951	53.86	gold quality
lower esophagus mucosa	UBERON:0035834	50.73	gold quality
cortical plate	UBERON:0005343	50.56	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
upper leg skin	UBERON:0004262	48.95	silver quality
thymus	UBERON:0002370	48.93	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
esophagus mucosa	UBERON:0002469	48.65	gold quality
metanephric glomerulus	UBERON:0004736	47.83	gold quality
renal glomerulus	UBERON:0000074	47.64	gold quality
quadriceps femoris	UBERON:0001377	47.60	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
vastus lateralis	UBERON:0001379	46.93	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
nephron tubule	UBERON:0001231	46.71	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
nasal cavity epithelium	UBERON:0005384	44.87	gold quality
bone marrow cell	CL:0002092	44.70	gold quality
layer of synovial tissue	UBERON:0007616	44.13	gold quality
body of tongue	UBERON:0011876	44.08	gold quality
sural nerve	UBERON:0015488	44.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB

miRNA regulators (miRDB)

6 targeting MC5R, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-4303	98.01	68.13	2304

Literature-anchored findings (GeneRIF, showing 12)

• Outlining the ligand recognition sites in the melanocortin receptors. (PMID:15470082)
• Variations in the melanocortin 5 receptor gene are unlikely to confer susceptibility to bipolar disorder in this sample. (PMID:16314755)
• Further structure-activity studies of lactam derivatives of MT-II and SHU-9119 were made at MC5R. (PMID:17482720)
• MC5R signals through a PI3K-regulated Akt-independent pathway leading to downstream activation of ERK1/2 (PMID:19428994)
• Data suggest that antagonists of MC1R and MC5R could be effective inhibitors of sebaceous gland differentiation and the production of sebum-specific lipids. (PMID:21602033)
• Melanocortin 5 receptor signaling and internalization: role of MAPK/ERK pathway and beta-arrestins 1/2. (PMID:22871966)
• D115 and D119 in TM3, F195 in TM5, and F254 in TM6 may form a binding pocket for NDP-alpha-MSH binding. (PMID:23414113)
• MC2R and MC1R signals are consecutively required for the regulation of EPO signal transduction in erythroblast differentiation, and MC5R signal transduction is required to induce enucleation. (PMID:25860801)
• melanocortin receptors MC2R, MC3R and MC5R are most abundantly expressed in glandular epithelium of the endometrium (PMID:26223677)
• Mutations in residues S4/S5 and S17/E18 retained MC5R at the ER/Golgi complex and did not affect MC5R homodimerization. (PMID:28396017)
• MCR5 is a modulator of the responses stimulated by glucose in ARPE-19 cells, which might possibly be translated into a modulation of the retinal pigment epithelium response to diabetes in vivo. (PMID:30739530)
• Evaluation of perilipin 2 and melanocortin 5 receptor serum levels with sebogenesis in acne vulgaris patients. (PMID:33765750)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mc5ra	ENSDARG00000031348
danio_rerio	mc5rb	ENSDARG00000054946
mus_musculus	Mc5r	ENSMUSG00000007480
rattus_norvegicus	Mc5r	ENSRNOG00000016685

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Melanocortin receptor 5 — P33032 (reviewed: P33032)

Alternative names: MC-2

All UniProt accessions (1): P33032

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. Also activates ERK1/2 via a PI3K-dependent signaling mechanism. Order of potency of natural melanocortins in receptor activation is alpha-MSH > ACTH > beta-MSH > gamma-MSH. Plays a key role in immune response, and is essential for temperature regulation and exocrine gland function.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the brain but not in the melanoma cells.

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

RefSeq proteins (1): NP_005904* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000621	Melancort_rcpt_5	Family
IPR001671	Melcrt_ACTH_rcpt	Family
IPR001908	MC3-5R	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (67 total): mutagenesis site 17, helix 11, topological domain 8, transmembrane region 7, turn 5, glycosylation site 4, strand 4, binding site 3, sequence conflict 3, lipid moiety-binding region 2, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8IOD	ELECTRON MICROSCOPY	2.59
8INR	ELECTRON MICROSCOPY	2.73
9K3H	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33032-F1	82.70	0.58

Antibody-complex structures (SAbDab): 2 — 8IOD, 9K3H

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 (2): 311, 312

Disulfide bonds (1): 264–270

Glycosylation sites (4): 2, 15, 20, 28

Mutagenesis-validated functional residues (17):

Position	Phenotype
92	over 100 fold decrease in alpha-msh potency.
99	10 to 100 fold alpha-msh potency.
115	impaired alpha-msh potency.
116	2 to 10 fold decrease in alpha-msh potency.
118	2 to 10 fold decrease in alpha-msh potency.
119	over 100 fold decrease in alpha-msh potency.
126	2 to 10 fold decrease in alpha-msh potency.
178	over 100 fold decrease in alpha-msh potency.
181	2 to 10 fold decrease in alpha-msh potency.
186	2 to 10 fold decrease in alpha-msh potency.
187	2 to 10 fold decrease in alpha-msh potency.
190	2 to 10 fold decrease in alpha-msh potency.
235	10% increase of binding to alpha-msh.
254	over 100 fold decrease in alpha-msh potency.
272	690% increase of binding to alpha-msh.
277	10 to 100 fold decrease in alpha-msh potency.
281	10 to 100 fold decrease in alpha-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: 141 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, MORF_FLT1, MORF_MSH3, MORF_BRCA1, MORF_ATRX, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, MORF_ESR1, MORF_RAD51L3, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_EXOCYTOSIS, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (8): temperature homeostasis (GO:0001659), 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), positive regulation of exocytosis (GO:0045921), negative regulation of immune response (GO:0050777), positive regulation of ERK1 and ERK2 cascade (GO:0070374), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (6): melanocortin receptor activity (GO:0004977), corticotropin receptor activity (GO:0004978), melanocyte-stimulating hormone receptor activity (GO:0004980), hormone binding (GO:0042562), 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	2
melanocortin receptor activity	2
hormone binding	2
binding	2
cellular anatomical structure	2
multicellular organismal-level homeostasis	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
exocytosis	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
negative regulation of immune system process	1
immune response	1
negative regulation of response to stimulus	1
regulation of immune response	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	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
G protein-coupled peptide receptor activity	1
neuropeptide receptor activity	1
transmembrane signaling receptor activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MC5R	POMC	P01189	997
MC5R	MRAP2	Q96G30	777
MC5R	AGRP	O00253	687
MC5R	MT2A	P02795	649
MC5R	ASIP	P42127	646
MC5R	MRAP	Q8TCY5	589
MC5R	RHO	P08100	563
MC5R	LEP	P41159	523
MC5R	ATP7A	Q04656	511
MC5R	MC1R	Q01726	500
MC5R	NPY	P01303	490
MC5R	MCHR1	Q99705	483
MC5R	AGT	P01019	452
MC5R	NPY2R	P49146	426
MC5R	SST	P01166	425

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MRAP2	MC5R	psi-mi:“MI:0915”(physical association)	0.400
MRAP	MC5R	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): MC5R (Reconstituted Complex)

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

17 interactions.

A	Effect	B	Mechanism
POMC	up-regulates	MC5R	binding
MC5R	“up-regulates activity”	GNAS	binding
MC5R	“up-regulates activity”	GNAL	binding
MC5R	“up-regulates activity”	GNAI1	binding
MC5R	“up-regulates activity”	GNAI3	binding
MC5R	“up-regulates activity”	GNAZ	binding
MC5R	“up-regulates activity”	GNAQ	binding
MC5R	“up-regulates activity”	GNA14	binding
MC5R	“up-regulates activity”	GNA12	binding
“MSH release-inhibiting hormone”	“up-regulates activity”	MC5R	“chemical activation”
ASIP	“down-regulates activity”	MC5R	binding
AGRP	“down-regulates activity”	MC5R	binding
POMC	“up-regulates activity”	MC5R	binding
Corticotropin	“up-regulates activity”	MC5R	binding
MRAP	“down-regulates activity”	MC5R	binding
MRAP2	“down-regulates activity”	MC5R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564565	GRCh37/hg19 18p11.32-11.21(chr18:136226-15198990)x4	Pathogenic

SpliceAI

198 predictions. Top by Δscore:

Variant	Effect	Δscore
18:13826471:G:GT	donor_gain	0.8100
18:13826317:C:G	donor_gain	0.7500
18:13826473:C:T	donor_gain	0.7100
18:13826317:C:CG	donor_gain	0.6900
18:13826412:TC:T	donor_gain	0.6900
18:13826472:G:T	donor_gain	0.6900
18:13826468:C:T	donor_gain	0.6700
18:13826458:G:GT	donor_gain	0.6600
18:13826498:G:GT	donor_gain	0.6400
18:13826304:ACTC:A	donor_gain	0.6300
18:13826479:C:A	donor_gain	0.6200
18:13826181:ATAG:A	donor_loss	0.6000
18:13826182:TAGG:T	donor_loss	0.6000
18:13826183:AGGTA:A	donor_loss	0.6000
18:13826184:GG:G	donor_loss	0.6000
18:13826185:GTAC:G	donor_loss	0.6000
18:13826186:T:A	donor_loss	0.6000
18:13826475:C:CA	donor_gain	0.6000
18:13826562:A:AG	acceptor_gain	0.6000
18:13826563:G:GG	acceptor_gain	0.6000
18:13826377:G:GG	donor_gain	0.5900
18:13826386:C:G	acceptor_gain	0.5900
18:13826180:GATAG:G	donor_gain	0.5800
18:13826388:T:G	acceptor_gain	0.5800
18:13826480:ACC:A	donor_gain	0.5700
18:13826500:C:T	donor_gain	0.5700
18:13826478:TC:T	donor_gain	0.5500
18:13826495:C:G	donor_gain	0.5500
18:13826352:C:G	donor_gain	0.5400
18:13826381:A:G	donor_gain	0.5400

AlphaMissense

2167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:13825994:A:C	S77R	0.995
18:13825996:C:A	S77R	0.995
18:13825996:C:G	S77R	0.995
18:13826159:A:C	S132R	0.991
18:13826161:C:A	S132R	0.991
18:13826161:C:G	S132R	0.991
18:13826021:A:C	S86R	0.987
18:13826023:C:A	S86R	0.987
18:13826023:C:G	S86R	0.987
18:13825913:A:C	S50R	0.983
18:13825915:C:A	S50R	0.983
18:13825915:C:G	S50R	0.983
18:13826264:T:A	W167R	0.983
18:13826264:T:C	W167R	0.983
18:13826198:T:C	F145L	0.979
18:13826200:C:A	F145L	0.979
18:13826200:C:G	F145L	0.979
18:13825927:C:A	N54K	0.976
18:13825927:C:G	N54K	0.976
18:13826504:T:C	F247L	0.976
18:13826506:T:A	F247L	0.976
18:13826506:T:G	F247L	0.976
18:13826181:A:T	D139V	0.974
18:13826273:T:C	C170R	0.974
18:13826181:A:C	D139A	0.973
18:13825926:A:T	N54I	0.972
18:13825926:A:C	N54T	0.969
18:13826184:G:T	R140M	0.969
18:13825947:T:A	I61K	0.968
18:13826275:C:G	C170W	0.967

dbSNP variants (sampled 300 via entrez): RS1000477574 (18:13823793 A>G), RS1000508528 (18:13823052 C>G,T), RS1001735448 (18:13822558 G>A), RS1002328102 (18:13826450 C>A,T), RS1003768749 (18:13826927 T>C), RS1003977500 (18:13827722 C>T), RS1004717815 (18:13824084 C>G,T), RS1005511237 (18:13826891 T>G), RS1006392894 (18:13822334 C>T), RS1006495183 (18:13824641 C>T), RS1006689447 (18:13826500 C>A,T), RS1007236921 (18:13826152 C>T), RS1007668616 (18:13824303 G>A), RS1007873046 (18:13824840 C>CTAATAAACTATCA), RS1008504766 (18:13824526 G>A)

Disease associations

OMIM: gene MIM:600042 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003830_17	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	8.000000e-07
GCST003830_48	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	5.000000e-07
GCST006427_34	Depression in smokers	5.000000e-06
GCST010922_14	Hip bone mineral density and total body fat mass (bivariate analysis)	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111397 (SELECTIVITY GROUP), CHEMBL4523974 (SELECTIVITY GROUP), CHEMBL4608 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 763,900 (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
CHEMBL11359	CISPLATIN	4
CHEMBL1201469	GRAMICIDIN	4
CHEMBL2070241	BREMELANOTIDE	4	157
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL3301624	SETMELANOTIDE	4	679
CHEMBL428647	PACLITAXEL	4	332,542
CHEMBL441738	AFAMELANOTIDE	4	602
CHEMBL6067481	COLISTIN	4
CHEMBL633	AMIODARONE	4	29,704
CHEMBL71	CHLORPROMAZINE	4	45,827
CHEMBL726	FLUPHENAZINE	4	23,313
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL809	SERTRALINE	4	51,342
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL91	MICONAZOLE	4	45,914
CHEMBL214332	INTERMEDINE	2	2,391
CHEMBL7002	CIGLITAZONE	2	13,404
CHEMBL4802244	DERSIMELAGON PHOSPHATE	1

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 (13 total), top 13:

Ligand	Action	Affinity	Parameter
PG-901	Full agonist	10.5	pIC50
MT-II	Full agonist	9.0	pIC50
afamelanotide	Full agonist	9.0	pIC50
SHU9119	Partial agonist	9.0	pKd
[125I]NDP-MSH	Full agonist	8.6	pKd
HS024	Antagonist	8.5	pKd
Ac-c[Cys-Glu-His-D-Phe-Arg-Trp-D-Cys]-Pro-Pro-Lys-Asp-NH2	Antagonist	8.0	pIC50
bremelanotide	Agonist	7.77	pKi
α-MSH	Full agonist	6.9	pKd
agouti-related protein	Inverse agonist	6.5	pIC50
setmelanotide	Agonist	6.37	pKi
ACTH	Agonist	5.0	pKi
agouti	Inverse agonist	4.9	pKd

Binding affinities (BindingDB)

19 measured of 503 human assays (503 total across all organisms); most potent 19 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
N-[[(3S,5S)-3-[3-(diaminomethylideneamino)propyl]-1-(2,2-diphenylethyl)-2-oxo-1,4-diazepan-5-yl]methyl]naphthalene-2-carboxamide	IC50	500 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor
NSC_123787	KI	784 nM
N-[[(3S,5R)-3-[3-(diaminomethylideneamino)propyl]-1-(2,2-diphenylethyl)-2-oxo-1,4-diazepan-5-yl]methyl]naphthalene-2-carboxamide	IC50	1500 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor
(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
(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
N-[[(3R,5S)-3-[3-(diaminomethylideneamino)propyl]-1-(2,2-diphenylethyl)-2-oxo-1,4-diazepan-5-yl]methyl]naphthalene-2-carboxamide	IC50	3500 nM	US-9340517: Methods of modulating the activity of the MC5 receptor and treatment of conditions related to this receptor

ChEMBL bioactivities

980 potent at pChembl≥5 of 1138 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.57	IC50	0.027	nM	CHEMBL1161313
10.51	EC50	0.031	nM	CHEMBL2371966
10.51	EC50	0.031	nM	CHEMBL1161313
10.51	IC50	0.031	nM	CHEMBL1161322
10.14	EC50	0.072	nM	CHEMBL4792986
10.14	EC50	0.072	nM	CHEMBL1161322
10.05	Ki	0.09	nM	CHEMBL442504
10.05	IC50	0.09	nM	CHEMBL2096742
10.00	IC50	0.1	nM	CHEMBL220018
10.00	IC50	0.1	nM	CHEMBL425442
9.96	IC50	0.11	nM	CHEMBL1161323
9.92	EC50	0.12	nM	CHEMBL442504
9.92	EC50	0.12	nM	CHEMBL2096742
9.82	IC50	0.15	nM	CHEMBL2371966
9.77	Ki	0.17	nM	CHEMBL415165
9.70	EC50	0.2	nM	CHEMBL1161323
9.66	EC50	0.22	nM	CHEMBL408843
9.64	EC50	0.23	nM	CHEMBL2371969
9.64	EC50	0.23	nM	AFAMELANOTIDE
9.59	Ki	0.26	nM	CHEMBL414718
9.54	EC50	0.29	nM	CHEMBL2371971
9.52	EC50	0.3	nM	CHEMBL501592
9.43	EC50	0.37	nM	CHEMBL2371962
9.41	Ki	0.39	nM	CHEMBL408843
9.40	IC50	0.4	nM	CHEMBL218558
9.40	EC50	0.4	nM	AFAMELANOTIDE
9.38	IC50	0.42	nM	CHEMBL4060000
9.35	EC50	0.45	nM	CHEMBL2371967
9.33	Ki	0.47	nM	CHEMBL2070245
9.32	Ki	0.48	nM	AFAMELANOTIDE
9.30	IC50	0.5	nM	CHEMBL218361
9.24	EC50	0.58	nM	AFAMELANOTIDE
9.15	IC50	0.7	nM	CHEMBL501592
9.15	Ki	0.71	nM	CHEMBL1923667
9.14	IC50	0.72	nM	CHEMBL2371962
9.12	Ki	0.76	nM	CHEMBL1923665
9.10	EC50	0.8	nM	CHEMBL3601428
9.10	IC50	0.8	nM	CHEMBL387169
9.08	Ki	0.84	nM	CHEMBL266879
9.07	IC50	0.86	nM	AFAMELANOTIDE
9.05	IC50	0.9	nM	CHEMBL2096742
9.05	IC50	0.89	nM	AFAMELANOTIDE
9.03	EC50	0.93	nM	CHEMBL4061566
9.02	IC50	0.95	nM	CHEMBL2371968
9.00	Ki	1	nM	CHEMBL2370964
9.00	EC50	1	nM	AFAMELANOTIDE
9.00	EC50	1	nM	CHEMBL4093140
9.00	EC50	1	nM	CHEMBL2371970
9.00	EC50	0.99	nM	CHEMBL2371968
9.00	EC50	1.01	nM	CHEMBL313279

PubChem BioAssay actives

942 with measured affinity, of 2124 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
(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	109293: Binding affinity against human Melanocortin 5 receptor	ec50	<0.0001	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	109308: Binding affinity against human Melanocortin 5 receptor	ic50	<0.0001	uM
(3S,6S,12S,20S,23S,26S)-12-[[(2S)-2-acetamidohexanoyl]amino]-23-(1H-indol-3-ylmethyl)-2,5,11,14,22,25-hexaoxo-3-[(4-phenylphenyl)methyl]-1,4,10,15,21,24-hexazatricyclo[24.4.0.06,10]triacontane-20-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	<0.0001	uM
(3S,11S,14S,17S,20R,23S)-3-[[(2S)-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	1954053: Agonist activity at human melanocortin receptor 5	ec50	0.0001	uM
N-[(2S)-1-[(3S,8aS)-3-benzyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-3-(1H-indol-3-yl)propanamide	274312: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells	ic50	0.0001	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	223528: Signal transduction efficacy in cAMP assay in CHO cells expressing human melanocortin receptor 5	ec50	0.0001	uM
(1R,4S,7R,10S,13S,21R,24R,29R)-21-[[(2R)-2-acetamidohexanoyl]amino]-7-[3-(diaminomethylideneamino)propyl]-10-(1H-indol-3-ylmethyl)-24,29-dimethyl-4-(naphthalen-2-ylmethyl)-2,5,8,11,19,22-hexaoxo-3,6,9,12,18,23-hexazatricyclo[21.7.0.024,29]triacontane-13-carboxamide	109307: Binding affinity against human Melanocortin 5 receptor	ic50	0.0001	uM
4-[(3R,8aS)-3-benzyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-N-[2-(1H-indol-3-yl)ethyl]-4-oxobutanamide	274312: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells	ic50	0.0001	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	109293: Binding affinity against human Melanocortin 5 receptor	ec50	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	109299: Effective concentration required for intracellular cAMP accumulation by Melanocortin 5 receptor	ec50	0.0002	uM
3-[(4R,10R,13S,16S,19S,22R,25S)-25-acetamido-4-carbamoyl-13-[3-(diaminomethylideneamino)propyl]-19-(1H-imidazol-5-ylmethyl)-10-(1H-indol-3-ylmethyl)-16-(naphthalen-2-ylmethyl)-6,9,12,15,18,21,24-heptaoxo-1,2-dithia-5,8,11,14,17,20,23-heptazacyclohexacos-22-yl]propanoic acid	223529: Increase in intracellular cAMP in CHO cells expressing human melanocortin receptor 5.	ec50	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	239514: Inhibition of [125I]NDP-alpha-MSH binding to melanocortin-5 receptor expressed in HEK293 cells	ki	0.0002	uM
(3S,6S,9S,17S,20S,23S)-9-[[(2S)-2-acetamidohexanoyl]amino]-20-(1H-indol-3-ylmethyl)-2,5,8,11,19,22-hexaoxo-3-[(4-phenylphenyl)methyl]-6-propan-2-yl-1,4,7,12,18,21-hexazabicyclo[21.4.0]heptacosane-17-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	0.0002	uM
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamidohexanoyl]amino]-25-(diaminomethylideneamino)-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	375550: Agonist activity at human MC5R expressed in HEK293 cells assessed as stimulation of intracellular cAMP level	ec50	0.0003	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	239514: Inhibition of [125I]NDP-alpha-MSH binding to melanocortin-5 receptor expressed in HEK293 cells	ki	0.0003	uM
(3S,6S,9S,17S,20S,23S)-9-[[(2S)-2-acetamidohexanoyl]amino]-20-(1H-indol-3-ylmethyl)-2,5,8,11,19,22-hexaoxo-6-phenyl-3-[(4-phenylphenyl)methyl]-1,4,7,12,18,21-hexazabicyclo[21.4.0]heptacosane-17-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	0.0003	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]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-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1477004: Displacement of [125I]-NDP-alpha-MSH from human MC5R expressed in HEK293 cells after 40 mins by gamma counting method	ic50	0.0004	uM
N-[6-[(3S,8aS)-3-benzyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-6-oxohexyl]-3-(1H-indol-3-yl)propanamide	274312: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells	ic50	0.0004	uM
(3S,6S,9S,17S,20S,23S)-9-[[(2S)-2-acetamidohexanoyl]amino]-6-(1H-imidazol-5-ylmethyl)-20-(1H-indol-3-ylmethyl)-2,5,8,11,19,22-hexaoxo-3-[(4-phenylphenyl)methyl]-1,4,7,12,18,21-hexazabicyclo[21.4.0]heptacosane-17-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	0.0004	uM
(1S,4S,11S,14S,17S,25S)-25-[[(2S)-2-acetamidohexanoyl]amino]-14-(1H-indol-3-ylmethyl)-2,5,12,15,23,26-hexaoxo-4-[(4-phenylphenyl)methyl]-3,6,13,16,22,27-hexazatetracyclo[25.8.0.06,11.029,34]pentatriaconta-29,31,33-triene-17-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	0.0004	uM
4-[(3S,8aS)-3-benzyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-N-[2-(1H-indol-3-yl)ethyl]-4-oxobutanamide	274312: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells	ic50	0.0005	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(3S,12S,15S,18S,21R,24S,26R)-21-benzyl-12-carbamoyl-18-[3-(diaminomethylideneamino)propyl]-26-hydroxy-15-(1H-indol-3-ylmethyl)-2,6,14,17,20,23-hexaoxo-1,7,13,16,19,22-hexazabicyclo[22.3.0]heptacosan-3-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-6-(diaminomethylideneamino)-1-oxohexan-2-yl]-2-[[(2S)-2-[[2-(hexadecanoylamino)acetyl]amino]-3-hydroxypropanoyl]amino]pentanediamide	677160: Displacement of [125I]-NAD-alpha-MSH from human recombinant MC3 receptor human MC5 expressed in BHK570 cells after 1 hr in presence of ovalbumin	ki	0.0005	uM
(3S)-3-[[(2R)-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-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	632882: Displacement of Eu-NDP-alphaMSH from human MC5 receptor expressed in human HEK293 cells after 1.5 hrs by time-resolved fluorescence analysis	ki	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)-1,4,7,13-tetramethyl-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1239138: Agonist activity at human MC5 receptor expressed in HEK293 cells assessed as intracellular cAMP accumulation using [3H]-cAMP by luminescence counting	ec50	0.0008	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-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-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	239514: Inhibition of [125I]NDP-alpha-MSH binding to melanocortin-5 receptor expressed in HEK293 cells	ki	0.0008	uM
1-[(3S,8aS)-3-benzyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-3-(1H-indol-3-yl)propan-1-one	274312: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells	ic50	0.0008	uM
(3S)-3-[[(2R)-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-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-5-carbamimidamidopentanoyl]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-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	632882: Displacement of Eu-NDP-alphaMSH from human MC5 receptor expressed in human HEK293 cells after 1.5 hrs by time-resolved fluorescence analysis	ki	0.0008	uM
(3S,11S,14S,17S,20R,23S)-3-[[(2S)-2-acetamidohexanoyl]amino]-20-benzyl-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-2,5,13,16,19,22-hexaoxo-1,6,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	1428592: Agonist activity at human MC5R expressed in CHO cells assessed as increase in IBMX-induced cAMP accumulation after 40 mins	ec50	0.0009	uM
(1S,4S,11S,14S,17S,25S)-25-[[(2S)-2-acetamidohexanoyl]amino]-14-(1H-indol-3-ylmethyl)-2,5,12,15,23,26-hexaoxo-4-[(4-phenylphenyl)methyl]-3,6,13,16,22,27-hexazatetracyclo[25.7.0.06,11.028,33]tetratriacontane-17-carboxamide	286940: Displacement of [125I]NDPalphaMSH from human cloned MC5R expressed in CHO cells	ic50	0.0009	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	1477006: Agonist activity at human MC5R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins	ec50	0.0010	uM
(2S,5R,8S,11R,14R)-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	109300: Effective concentration against human melanocortin 5 receptor (hMC5R) in HEK293 cells	ec50	0.0010	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	109433: Binding affinity against human Melanocortin 5 receptor by gamma-MCH displacement.	ki	0.0010	uM
(3S,6S,9S,17S,20S,23S)-9-[[(2S)-2-acetamidohexanoyl]amino]-6-cyclohexyl-20-(1H-indol-3-ylmethyl)-2,5,8,11,19,22-hexaoxo-3-[(4-phenylphenyl)methyl]-1,4,7,12,18,21-hexazabicyclo[21.4.0]heptacosane-17-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	0.0010	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)-1,4,13-trimethyl-9-(naphthalen-2-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	1239138: Agonist activity at human MC5 receptor expressed in HEK293 cells assessed as intracellular cAMP accumulation using [3H]-cAMP by luminescence counting	ec50	0.0011	uM
(3S,11S,14S,17S,20R,23S,25S)-3-[[(2S)-2-acetamidohexanoyl]amino]-20-benzyl-25-(diaminomethylideneamino)-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-2,5,13,16,19,22-hexaoxo-1,6,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	375546: Displacement of [125I][Nle4,Dphe7]-alpha-MSH from human MC5R expressed in HEK293 cells	ic50	0.0011	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(3S,12S,15S,18S,21R,24S,26R)-21-benzyl-18-(3-carbamimidamidopropyl)-12-carbamoyl-26-hydroxy-15-(1H-indol-3-ylmethyl)-2,6,14,17,20,23-hexaoxo-1,7,13,16,19,22-hexazabicyclo[22.3.0]heptacosan-3-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-2-[[(2S)-2-[[2-[4-(hexadecanoylsulfamoyl)butanoylamino]acetyl]amino]-3-hydroxypropanoyl]amino]pentanediamide	677160: Displacement of [125I]-NAD-alpha-MSH from human recombinant MC3 receptor human MC5 expressed in BHK570 cells after 1 hr in presence of ovalbumin	ki	0.0012	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	109308: Binding affinity against human Melanocortin 5 receptor	ic50	0.0012	uM
(2S,5S,8R,11S,14S,17S)-5-(3-amino-3-oxopropyl)-2-butyl-11-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-8-(naphthalen-2-ylmethyl)-3,6,9,12,15,20-hexaoxo-1,4,7,10,13,16-hexazacycloicosane-17-carboxamide	261682: Inhibitory activity against hMC5R transfected in HEK293 cells	ic50	0.0014	uM
(3S)-3-[[(2R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-6-(hex-5-ynoylamino)hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-5-carbamimidamidopentanoyl]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-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	632882: Displacement of Eu-NDP-alphaMSH from human MC5 receptor expressed in human HEK293 cells after 1.5 hrs by time-resolved fluorescence analysis	ki	0.0014	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	109298: Effective concentration that was able to generate 50% maximal intracellular cAMP in L-cells transfected with Melanocortin 5 receptor	ec50	0.0015	uM
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamidohexanoyl]amino]-20-benzyl-25-(diaminomethylideneamino)-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-2,5,13,16,19,22-hexaoxo-1,6,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	375550: Agonist activity at human MC5R expressed in HEK293 cells assessed as stimulation of intracellular cAMP level	ec50	0.0016	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(3S,12S,15S,18S,21R,24S,26R)-21-benzyl-12-carbamoyl-18-[3-(diaminomethylideneamino)propyl]-26-hydroxy-15-(1H-indol-3-ylmethyl)-2,6,14,17,20,23-hexaoxo-1,7,13,16,19,22-hexazabicyclo[22.3.0]heptacosan-3-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-2-[[(2S)-2-[[2-(hexadecanoylamino)acetyl]amino]-3-hydroxypropanoyl]amino]pentanediamide	677160: Displacement of [125I]-NAD-alpha-MSH from human recombinant MC3 receptor human MC5 expressed in BHK570 cells after 1 hr in presence of ovalbumin	ki	0.0016	uM
(3S,6S,12S,20S,23S,26S)-12-[[(2S)-2-acetamidohexanoyl]amino]-23-(1H-indol-3-ylmethyl)-2,5,11,14,22,25-hexaoxo-3-[(4-phenylphenyl)methyl]-1,4,10,15,21,24-hexazatricyclo[24.3.0.06,10]nonacosane-20-carboxamide	286947: Agonist activity at human MC5R expressed in CHO cells assessed as cAMP accumulation	ec50	0.0016	uM
(3S)-3-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]butanoyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-naphthalen-2-ylpropanoyl]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	109304: Intracellular cAMP accumulation in human Melanocortin 5 receptor functional assay.	ec50	0.0018	uM
(11S,14S,17S,20R,23S)-20-benzyl-17-[3-(diaminomethylideneamino)propyl]-23-(1H-imidazol-5-ylmethyl)-14-(1H-indol-3-ylmethyl)-8,13,16,19,22,25-hexaoxo-7,12,15,18,21,24-hexazaspiro[5.19]pentacosane-11-carboxamide	1369757: Agonist activity at human MC5R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins	ec50	0.0019	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]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-[(2-aminooxy-2-oxoethyl)amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	246688: Effective concentration for intracellular cAMP accumulation in human melanocortin 5 receptor expressing HEK 293 cells; (N = 4)	ec50	0.0019	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]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-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1477006: Agonist activity at human MC5R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins	ec50	0.0019	uM
(2S,5S,8R,11S,14S,17S)-2-butyl-11-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-8-(naphthalen-2-ylmethyl)-3,6,9,12,15,20-hexaoxo-5-propan-2-yl-1,4,7,10,13,16-hexazacycloicosane-17-carboxamide	261686: Activity against hMC5R transfected in HEK293 cells by intracellular cAMP accumulation	kd	0.0020	uM
(9S,12S,15S,18R,21S)-18-benzyl-15-[3-(diaminomethylideneamino)propyl]-21-(1H-imidazol-5-ylmethyl)-12-(1H-indol-3-ylmethyl)-6,11,14,17,20,23-hexaoxo-5,10,13,16,19,22-hexazaspiro[3.19]tricosane-9-carboxamide	1369757: Agonist activity at human MC5R expressed in HEK293 cells assessed as induction of intracellular cAMP accumulation after 3 mins	ec50	0.0020	uM
(5R,8S,11S,14R,17S,20R)-20-[[(2S)-2-acetamidohexanoyl]amino]-14-benzyl-11-[3-(diaminomethylideneamino)propyl]-17-(1H-imidazol-5-ylmethyl)-8-(1H-indol-3-ylmethyl)-7,10,13,16,19-pentaoxo-3,22-dithia-6,9,12,15,18-pentazabicyclo[22.2.2]octacosa-1(26),24,27-triene-5-carboxamide	1902921: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells by competitive binding assay	ic50	0.0020	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aminomethylphosphonic acid (AMPA)	increases expression	1
bisphenol A	decreases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
indole	affects binding	1
naphthalene	affects binding	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
licochalcone B	increases expression	1
Benzo(a)pyrene	increases methylation	1
Phthalic Acids	decreases methylation	1
Silicon Dioxide	increases expression	1
2,4-Dichlorophenoxyacetic Acid	increases expression	1
Isotretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

246 unique, capped per target: 132 binding, 110 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL825473	Functional	Selectivity for melanocortin 4 receptor compared to melanocortin 5 receptor in vitro	Melanocortin subtype-4 receptor agonists containing a piperazine core with substituted aryl sulfonamides. — Bioorg Med Chem Lett
CHEMBL831728	Binding	Selectivity of human melanocortin subtype-5 receptor over human melanocortin-4 receptor was determined	Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist. — Bioorg Med Chem Lett
CHEMBL4032187	ADMET	Displacement of [125I]-NDP-alpha-MSH from human MC5R 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

6 cell lines: 4 spontaneously immortalized cell line, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0T6	ACTOne MC5R	Transformed cell line	Female
CVCL_H462	CHO-K1/MC5/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV48	cAMP Hunter CHO-K1 MC5R Gs	Spontaneously immortalized cell line	Female
CVCL_KX99	PathHunter CHO-K1 MC5R beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA71	PathHunter U2OS MC5R beta-arrestin	Cancer cell line	Female
CVCL_ZK75	GeneBLAzer MC5R-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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