MC1R

Summary

MC1R (melanocortin 1 receptor, HGNC:6929) is a protein-coding gene on chromosome 16q24.3, encoding Melanocyte-stimulating hormone receptor (Q01726). G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein.

This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation.

Source: NCBI Gene 4157 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocutaneous albinism type 2 (Moderate, GenCC)
• GWAS associations: 91
• Clinical variants (ClinVar): 827 total — 1 likely-pathogenic
• Phenotypes (HPO): 43
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6929
Approved symbol	MC1R
Name	melanocortin 1 receptor
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	MSH-R
Ensembl gene	ENSG00000258839
Ensembl biotype	protein_coding
OMIM	155555
Entrez	4157

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000539976, ENST00000555147, ENST00000555427, ENST00000639847, ENST00000928269

RefSeq mRNA: 1 — MANE Select: NM_002386 NM_002386

CCDS: CCDS56011

Canonical transcript exons

ENST00000555147 — 1 exons

Exon	Start	End
ENSE00002458332	89918862	89920972

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 91.38.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6340 / max 122.3073, expressed in 802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155668	1.5232	465
155667	1.1108	411

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.38	gold quality
right uterine tube	UBERON:0001302	90.25	gold quality
left testis	UBERON:0004533	90.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.54	gold quality
adenohypophysis	UBERON:0002196	89.44	gold quality
cerebellar hemisphere	UBERON:0002245	89.41	gold quality
pituitary gland	UBERON:0000007	89.38	gold quality
right testis	UBERON:0004534	89.38	gold quality
cerebellar cortex	UBERON:0002129	89.23	gold quality
mucosa of stomach	UBERON:0001199	87.67	gold quality
cerebellum	UBERON:0002037	87.36	gold quality
left lobe of thyroid gland	UBERON:0001120	87.29	gold quality
testis	UBERON:0000473	86.36	gold quality
right lobe of thyroid gland	UBERON:0001119	86.03	gold quality
thyroid gland	UBERON:0002046	85.87	gold quality
type B pancreatic cell	CL:0000169	82.17	gold quality
left ovary	UBERON:0002119	82.15	gold quality
olfactory bulb	UBERON:0002264	81.94	gold quality
buccal mucosa cell	CL:0002336	81.83	silver quality
left uterine tube	UBERON:0001303	80.31	gold quality
endocervix	UBERON:0000458	80.22	gold quality
metanephros cortex	UBERON:0010533	80.21	gold quality
right ovary	UBERON:0002118	80.14	gold quality
stromal cell of endometrium	CL:0002255	79.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.20	gold quality
minor salivary gland	UBERON:0001830	79.17	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.08	gold quality
tongue squamous epithelium	UBERON:0006919	78.98	gold quality
body of uterus	UBERON:0009853	78.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.01

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TNF	Repression

Upstream regulators (CollecTRI, top): EDN1, IL1A, IL1B, IRF1, MITF, TBPL1, TNF

miRNA regulators (miRDB)

21 targeting MC1R, 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-4283	100.00	66.42	2097
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-1306-5P	97.11	64.04	755
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-711	96.60	65.75	528
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-3657	96.33	66.29	608

Literature-anchored findings (GeneRIF, showing 40)

• MC1R genotype modifies genetic susceptibility to melanoma in families with CDKN2A mutations. (PMID:11500805)
• mutations modify risk in Dutch families for melanoma (PMID:11500806)
• The human receptor efficiently rescued mouse Mc1r deficiency and appeared to be completely resistant to the effect of agouti, suggesting agouti protein may play a role in human pigmentary variation. (PMID:11689486)
• Four novel variants in MC1R in red-haired South African individuals of European descent: S83P, Y152X, A171D, P256S. (PMID:11933208)
• Loss-of-function mutations in the MC1R gene sensitize human melanocytes to the DNA damaging effects of UV radiation, which may increase skin cancer risk. (PMID:12006619)
• Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. (PMID:12177778)
• MC1R expression is regulated by microphthalmia-associated transcription factor (MITF) (PMID:12204775)
• the function of the MC1 and MC4 receptors can be positively modulated by metal ions acting both as partial agonists and as potentiators for other agonists (PMID:12244039)
• suggests an alternative non-pigmentary mechanism whereby MC1R variants could modify melanoma susceptibility or progression (PMID:12439754)
• Melanocortin 1 receptor is regulated by paracrine factors, including its own ligands, by specific endocrine sex hormones, and by UVR. (PMID:12453185)
• MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system (PMID:12473109)
• The MC1R gene probably does not play as significant role as other genes in the pigmentation variation between African and European populations. (PMID:12579416)
• Structural requirements that allow an active conformation without binding to a ligand, as a consequence of the E/K mutation, are not conserved within MC receptors; results are discussed in relationship to feather colour in chicken, structure and evolution (PMID:12653999)
• women with two variant MC1R alleles displayed significantly greater analgesia from the kappa-opioid, pentazocine, than all other groups (PMID:12663858)
• melanocortin-1 receptor has a role in skin cancer risk phenotypes through a polymorphism (PMID:12753400)
• A candidate gene for pigmentation. (PMID:12817591)
• Red hair in black Jamaicans is due to a mutation in MC1R. (PMID:12839583)
• data show considerable gene sequence variation with the detection of eight synonymous and three nonsynonymous mutations in normally pigmented African individuals (PMID:12851329)
• mutations in the MC1R gene were responsible for the red (rather than yellow/blond) hair in the six of eight who continued to have red hair after birth; the first demonstration of a gene modifying the oculocutaneous albinism phenotype in humans (PMID:12876664)
• There were no significant differences in the frequency of any of the five most common variants of MC1R between 62 ocular melanoma cases and ethnicity-matched population controls. (PMID:12883368)
• In a study of 20 persons, 10 of whom were homozygous for MC1R mutations, we measured erythema over a 21-day period in response to a range of ultraviolet B doses. We detected no consistent differences in UV B-induced erythema between the groups studied. (PMID:12930311)
• MC1R appears the limiting factor controlling the output of the cAMP signalling pathway (PMID:12950734)
• Strong association between functional MC1R variant alleles and malignant melanoma in the French population. (PMID:14757863)
• MC1R genotype was predictive of hair melanin expressed as the ratio of the loge of eumelanin to pheomelanin ratio, with a dosage effect evident (PMID:15009725)
• ultraviolet irradiation affects the expression of both alpha-melanocyte-stimulating hormone and the melanocortin-1 receptor in human epidermis in vivo (PMID:15009732)
• Eight novel MC1R missense mutations found Italians Melanoma patients. (PMID:15221796)
• UV-induced expression of POMC and MC1R is dependent on the p-38-activated upstream stimulating factor-1 (PMID:15358786)
• Outlining the ligand recognition sites in the melanocortin receptors. (PMID:15470082)
• Asp84Glu, Val92Met, Arg163Gln, and Asp294His variants of the human MC1 receptors differ in ability to bind alpha-melanocyte stimulating hormone (MSH) peptides and increase intracellular cAMP (PMID:15482480)
• melanocortin receptors (MC1R and MC3R) exist as constitutively pre-formed dimers (PMID:15582585)
• Melanocortin 1 receptor signaling is regulated by GRK2 and GRK6, which may be important determinants of skin pigmentation. (PMID:15650023)
• analysis of the highly polymorphic locus MC1R (PMID:15957185)
• Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. (PMID:15972726)
• review of polymorphism and selection at the MC1R coding and promoter regions in human populations, the pattern of MC1R evolution in nonhuman primates, and the interaction of MC1R with other genes [review] (PMID:15979202)
• The MC1R C-terminal pentapeptide is essential for proper receptor expression on the plasma membrane. (PMID:15993512)
• C57BL/6-Mc1r(e/e) mutant mice and human redheads–both with non-functional MC1Rs–display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the mu-opioid selective morphine metabolite, M6G. (PMID:15994880)
• MC1R was associated with melanoma risk and progression in a Mediterranean population, particularly in the absence of other strong risk factors, such as freckling or many nevi. (PMID:15998953)
• Dermal papilla cells expressed both MC1R and MC4R in vitro, and immunoreactivity for these receptors was also present in cells of the human dermal papilla in situ. (PMID:16081629)
• Cells expressing epitope-tagged MC1R revealed dimeric and oligomeric species in detergent-solubilized extracts. (PMID:16417234)
• Results describe the relative expression levels of both melanocortin-1 receptor mRNA and protein in a subset of different cell types. (PMID:16420249)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mc1r	ENSDARG00000020237
mus_musculus	Mc1r	ENSMUSG00000074037
rattus_norvegicus	Mc1r	ENSRNOG00000074229

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), 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), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Melanocyte-stimulating hormone receptor — Q01726 (reviewed: Q01726)

Alternative names: Melanocortin receptor 1

All UniProt accessions (3): Q01726, G3V4F0, Q1JUL4

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein. Upon activation, MC1R couples with the G(s) protein, stimulating adenylate cyclase and activating the cAMP-dependent signaling pathway. This activation promotes melanogenesis, resulting in the production of eumelanin (black/brown) and pheomelanin (red/yellow) in melanocytes. MC1R interacts with G protein-coupled receptor opsin 3/OPN3, which couples to G(i) proteins and inhibits the alpha-MSH-induced cAMP response, thereby reducing melanin synthesis. Binding to Agouti/ASP precludes alpha-MSH-induced signaling, thereby downregulating melanogenesis. Additionally, interaction with MGRN1 displaces the G(s) protein, further suppressing MC1R signaling.

Subunit / interactions. Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production. Interacts with OPN3; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes. Interacts with GNB1, the interaction is important for coupling of MC1R to G protein.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in melanocytes. Expressed in corticoadrenal tissue.

Disease relevance. Melanoma, cutaneous malignant 5 (CMM5) [MIM:613099] A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Polymorphism. Genetic variants in MC1R define the skin/hair/eye pigmentation variation locus 2 (SHEP2) [MIM:266300]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator, with type I skin being the most lightly pigmented and type IV the most dark pigmented. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. Partial loss-of-function mutations are associated with fair skin, poor tanning and increased skin cancer risk. MC1R variants associated with red hair and fair skin, determine female-specific increased analgesia from kappa-opioid receptor agonist [MIM:613098].

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

RefSeq proteins (1): NP_002377* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000761	MSH_rcpt	Family
IPR001671	Melcrt_ACTH_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (85 total): sequence variant 31, mutagenesis site 14, helix 12, topological domain 8, transmembrane region 7, binding site 3, sequence conflict 3, turn 2, chain 1, lipid moiety-binding region 1, glycosylation site 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7F4H	ELECTRON MICROSCOPY	2.7
7F4F	ELECTRON MICROSCOPY	2.9
9K3P	ELECTRON MICROSCOPY	2.98
7F4D	ELECTRON MICROSCOPY	3
7F4I	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01726-F1	80.62	0.33

Antibody-complex structures (SAbDab): 5 — 7F4D, 7F4F, 7F4H, 7F4I, 9K3P

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 (1): 267–273

Glycosylation sites (1): 29

Mutagenesis-validated functional residues (14):

Position	Phenotype
65	only minor effect on internalization rate and protein half-life; when associated with r-226; r-238 and r-310.
94	decreased alpha-msh binding affinity and camp response upon alpha-msh activation.
117	decreased alpha-msh binding affinity and camp response upon alpha-msh activation.
121	decreased alpha-msh binding affinity and camp response upon alpha-msh activation.
150	loss of coupling ability to g(s) and decreased camp response upon alpha-msh activation.
226	only minor effect on internalization rate and protein half-life; when associated with r-65; r-238 and r-310.
238	only minor effect on internalization rate and protein half-life; when associated with r-65; r-226 and r-310.
260	decreased alpha-msh binding affinity and camp response upon alpha-msh activation.
267	impaired alpha-msh binding affinity and camp response upon alpha-msh activation, when associated with a-273.
273	impaired alpha-msh binding affinity and camp response upon alpha-msh activation, when associated with a-267.
294	impaired camp response upon alpha-msh activation.
304	impaired camp response upon alpha-msh activation, when associated with a-307.
307	impaired camp response upon alpha-msh activation, when associated with a-304.
310	only minor effect on internalization rate and protein half-life; when associated with r-65; r-226 and r-238.

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: 214 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_POSITIVE_REGULATION_OF_BEHAVIOR, GOBP_UV_PROTECTION, GOBP_PIGMENTATION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_PAIN, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_REGULATION_OF_BEHAVIOR, GOBP_REGULATION_OF_FEEDING_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (18): 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), UV protection (GO:0009650), sensory perception of pain (GO:0019233), negative regulation of tumor necrosis factor production (GO:0032720), intracellular signal transduction (GO:0035556), melanin biosynthetic process (GO:0042438), pigmentation (GO:0043473), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of melanin biosynthetic process (GO:0048023), UV-damage excision repair (GO:0070914), positive regulation of cAMP/PKA signal transduction (GO:0141163), positive regulation of feeding behavior (GO:2000253), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), regulation of gene expression (GO:0010468), regulation of feeding behavior (GO:0060259)

GO Molecular Function (8): melanocortin receptor activity (GO:0004977), corticotropin receptor activity (GO:0004978), melanocyte-stimulating hormone receptor activity (GO:0004980), G protein-coupled peptide receptor activity (GO:0008528), ubiquitin protein ligase binding (GO:0031625), 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	3
intracellular anatomical structure	2
signal transduction	2
feeding behavior	2
G protein-coupled receptor activity	2
melanocortin receptor activity	2
hormone binding	2
binding	2
cellular anatomical structure	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
response to UV	1
sensory perception	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
melanin metabolic process	1
secondary metabolite biosynthetic process	1
pigment biosynthetic process	1
phenol-containing compound biosynthetic process	1
biological_process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
melanin biosynthetic process	1
regulation of melanin biosynthetic process	1
positive regulation of secondary metabolite biosynthetic process	1
DNA repair	1
cellular response to UV	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of behavior	1
regulation of feeding behavior	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MC1R	POMC	P01189	999
MC1R	ASIP	P42127	996
MC1R	TYR	P14679	959
MC1R	OCA2	Q04671	936
MC1R	TYRP1	P17643	933
MC1R	SLC45A2	Q9UMX9	907
MC1R	SLC24A5	Q71RS6	859
MC1R	MITF	O75030	844
MC1R	MTAP	Q13126	822
MC1R	CDKN2A	P42771	793
MC1R	ATRN	O75882	763
MC1R	DEFB103A	P81534	759
MC1R	STX17	P56962	757
MC1R	KIT	P10721	752
MC1R	DCT	P40126	752

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NFIC	NFIB	psi-mi:“MI:0914”(association)	0.690
OPN3	MC1R	psi-mi:“MI:0915”(physical association)	0.560
MC1R	OPN3	psi-mi:“MI:0915”(physical association)	0.560
OPN3	MC1R	psi-mi:“MI:0403”(colocalization)	0.560
MRAP2	MC1R	psi-mi:“MI:0915”(physical association)	0.400
MC1R	MRAP	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (22): MC1R (Affinity Capture-MS), MC1R (Affinity Capture-MS), MC1R (Affinity Capture-MS), ARRB2 (Affinity Capture-Western), MGRN1 (Affinity Capture-Western), MC1R (Affinity Capture-Western), MC1R (Affinity Capture-Western), MC1R (Affinity Capture-MS), MC1R (Affinity Capture-MS), MC1R (Reconstituted Complex), MC1R (Proximity Label-MS), MC1R (Affinity Capture-MS), MC1R (Affinity Capture-Western), MGRN1 (Affinity Capture-Western), MGRN1 (Affinity Capture-Western)

ESM2 similar proteins: C8YUV0, O19037, O77616, P31392, P43142, P55167, P56442, P56445, P56447, P56448, Q01726, Q29154, Q2AC31, Q5NUL3, Q6A155, Q7TMA4, Q7TQP3, Q80SS9, Q864F4, Q864F6, Q864F7, Q864F8, Q864H5, Q864H7, Q864H8, Q864H9, Q864I4, Q864I6, Q864I7, Q864J1, Q864J2, Q864J3, Q864J4, Q864J5, Q864J7, Q864J8, Q864J9, Q864K0, Q864K2, Q864K3

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

22 interactions.

A	Effect	B	Mechanism
POMC	“up-regulates activity”	MC1R	binding
MC1R	up-regulates	Pigmentation
MC1R	“down-regulates quantity by repression”	TNF	“transcriptional regulation”
ASIP	“down-regulates activity”	MC1R	binding
TNF	“down-regulates activity”	MC1R	“transcriptional regulation”
IL1B	“up-regulates quantity by expression”	MC1R	“transcriptional regulation”
EDN1	“up-regulates quantity by expression”	MC1R	“transcriptional regulation”
IL1A	“up-regulates quantity by expression”	MC1R	“transcriptional regulation”
“UVB radiation”	up-regulates	MC1R
GRK6	“down-regulates activity”	MC1R	phosphorylation
MC1R	“up-regulates activity”	GNAS	binding
MC1R	“up-regulates activity”	GNAQ	binding
MC1R	“up-regulates activity”	GNA14	binding
“MSH release-inhibiting hormone”	“up-regulates activity”	MC1R	“chemical activation”
AGRP	“down-regulates activity”	MC1R	binding
Corticotropin	“up-regulates activity”	MC1R	binding
ZDHHC13	“up-regulates activity”	MC1R	palmitoylation
MRAP	“down-regulates activity”	MC1R	binding
MRAP2	“down-regulates activity”	MC1R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	498
Likely benign	215
Benign	34

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
548661	NM_002386.4(MC1R):c.894C>G (p.Tyr298Ter)	Likely pathogenic

SpliceAI

578 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89920189:G:GT	donor_gain	1.0000
16:89918225:G:GT	donor_gain	0.9900
16:89920179:G:GT	donor_gain	0.9700
16:89920189:G:T	donor_gain	0.9700
16:89920227:GCTT:G	donor_gain	0.9700
16:89920735:G:GT	donor_gain	0.9700
16:89917930:G:GT	donor_gain	0.9600
16:89920206:CTG:C	donor_loss	0.9600
16:89920208:GGTGA:G	donor_loss	0.9600
16:89920209:GT:G	donor_loss	0.9600
16:89920210:T:TG	donor_loss	0.9600
16:89920211:GAGC:G	donor_loss	0.9600
16:89920212:AG:A	donor_loss	0.9500
16:89920528:T:A	acceptor_gain	0.9500
16:89920209:G:GG	donor_gain	0.9400
16:89920213:G:T	donor_loss	0.9400
16:89920529:G:A	acceptor_gain	0.9400
16:89917898:G:GT	donor_gain	0.9300
16:89917943:G:GG	donor_gain	0.9300
16:89918257:C:G	donor_gain	0.9100
16:89918038:G:GT	donor_gain	0.8800
16:89920219:TGC:T	donor_gain	0.8800
16:89918520:C:G	donor_gain	0.8600
16:89920250:G:T	donor_gain	0.8600
16:89917898:G:T	donor_gain	0.8300
16:89918042:C:T	donor_gain	0.8300
16:89917942:A:AG	donor_gain	0.8100
16:89920226:GGCTT:G	donor_gain	0.8100
16:89917931:A:T	donor_gain	0.7800
16:89920587:CAG:C	acceptor_gain	0.7700

AlphaMissense

2039 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:89919772:A:C	S172R	0.942
16:89919774:T:A	S172R	0.942
16:89919774:T:G	S172R	0.942
16:89919697:T:C	F147L	0.925
16:89919699:C:A	F147L	0.925
16:89919699:C:G	F147L	0.925
16:89919784:A:C	S176R	0.924
16:89919786:C:A	S176R	0.924
16:89919786:C:G	S176R	0.924
16:89919520:A:C	S88R	0.915
16:89919522:C:A	S88R	0.915
16:89919522:C:G	S88R	0.915
16:89919634:A:C	S126R	0.915
16:89919636:C:A	S126R	0.915
16:89919636:C:G	S126R	0.915
16:89919391:T:C	F45L	0.906
16:89919393:C:A	F45L	0.906
16:89919393:C:G	F45L	0.906
16:89919412:A:C	S52R	0.900
16:89919414:C:A	S52R	0.900
16:89919414:C:G	S52R	0.900
16:89919649:A:C	S131R	0.898
16:89919651:C:A	S131R	0.898
16:89919651:C:G	S131R	0.898
16:89920027:T:C	F257L	0.890
16:89920029:C:A	F257L	0.890
16:89920029:C:G	F257L	0.890
16:89919526:A:C	S90R	0.877
16:89919528:C:A	S90R	0.877
16:89919528:C:G	S90R	0.877

dbSNP variants (sampled 300 via entrez): RS1000053614 (16:89916921 G>A), RS1000245688 (16:89917358 C>T), RS1000298048 (16:89917029 G>A), RS1000459034 (16:89920287 C>A,T), RS1001383939 (16:89920617 G>C), RS1001434609 (16:89920985 C>T), RS1001699603 (16:89920919 C>T), RS1002284567 (16:89918481 C>G,T), RS1002483756 (16:89918736 C>G,T), RS1004532963 (16:89921161 G>A), RS1004647671 (16:89921320 G>A), RS1004998611 (16:89917929 G>A), RS1005394984 (16:89917911 C>A,T), RS1006456839 (16:89918846 C>A,G,T), RS1006964619 (16:89920362 C>T)

Disease associations

OMIM: gene MIM:155555 | disease phenotypes: MIM:613099, MIM:203200, MIM:155600

GenCC curated gene-disease

Disease	Classification	Inheritance
oculocutaneous albinism type 2	Moderate	Autosomal recessive

Mondo (8): melanoma, cutaneous malignant, susceptibility to, 5 (MONDO:0013133), oculocutaneous albinism type 2 (MONDO:0008746), melanoma (MONDO:0005105), breast cancer (MONDO:0007254), UV-induced skin damage, susceptibility to (MONDO:0800410), hereditary neoplastic syndrome (MONDO:0015356), familial melanoma (MONDO:0018961), melanoma, cutaneous malignant, susceptibility to, 1 (MONDO:0007963)

Orphanet (4): Familial melanoma (Orphanet:618), Oculocutaneous albinism type 2 (Orphanet:79432), Inherited cancer-predisposing syndrome (Orphanet:140162), NON RARE IN EUROPE: Melanoma (Orphanet:411533)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0000539	Abnormality of refraction
HP:0000545	Myopia
HP:0000577	Exotropia
HP:0000613	Photophobia
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000958	Dry skin
HP:0001010	Hypopigmentation of the skin
HP:0001022	Albinism
HP:0001100	Heterochromia iridis
HP:0001480	Freckling
HP:0001595	Abnormal hair morphology
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002226	White eyebrow
HP:0002227	White eyelashes
HP:0002297	Red hair
HP:0002671	Basal cell carcinoma
HP:0002861	Melanoma
HP:0002894	Neoplasm of the pancreas
HP:0003764	Nevus
HP:0005599	Hypopigmentation of hair
HP:0006739	Squamous cell carcinoma of the skin
HP:0006753	Neoplasm of the stomach
HP:0007481	Hyperpigmented nevi
HP:0007603	Freckles in sun-exposed areas
HP:0007663	Reduced visual acuity

GWAS associations

91 associations (top):

Study	Trait	p-value
GCST000115_1	Red vs non-red hair color	2.000000e-142
GCST000116_2	Skin sensitivity to sun	2.000000e-55
GCST000118_2	Blond vs. brown hair color	2.000000e-13
GCST000119_2	Freckles	1.000000e-96
GCST000191_4	Black vs. red hair color	2.000000e-23
GCST000371_10	Tanning	7.000000e-08
GCST000371_3	Tanning	3.000000e-09
GCST000437_1	Melanoma	6.000000e-22
GCST000437_4	Melanoma	3.000000e-27
GCST000707_1	Hair color	3.000000e-10
GCST000707_4	Hair color	5.000000e-87
GCST000708_2	Freckling	8.000000e-62
GCST001124_1	Basal cell carcinoma	4.000000e-17
GCST001267_2	Melanoma	3.000000e-27
GCST001509_4	Vitiligo	2.000000e-13
GCST001932_6	Hair color	3.000000e-09
GCST001933_4	Sunburns	2.000000e-19
GCST001939_4	Tanning	1.000000e-65
GCST001940_4	Non-melanoma skin cancer	3.000000e-10
GCST002514_6	Melanoma	2.000000e-09
GCST002785_3	Facial pigmentation	9.000000e-15
GCST002906_6	Skin colour saturation	3.000000e-15
GCST002907_3	Perceived skin darkness	1.000000e-06
GCST002908_3	Skin sensitivity to sun	8.000000e-23
GCST003019_2	Black vs. non-black hair color	4.000000e-09
GCST003020_1	Red vs non-red hair color	8.000000e-50
GCST003020_3	Red vs non-red hair color	1.000000e-55
GCST003021_1	Brown vs. non-brown hair color	5.000000e-10
GCST003021_8	Brown vs. non-brown hair color	9.000000e-12
GCST003022_1	Light vs. dark hair color	1.000000e-11

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0003963	freckles
EFO:0004279	suntan
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0009260	non-melanoma skin carcinoma
EFO:0004632	nevus count
EFO:0010176	keratinocyte carcinoma
EFO:0010483	gentisic acid measurement
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008545	Melanoma	C04.557.465.625.650.510; C04.557.580.625.650.510; C04.557.665.510; C04.588.805.377; C17.800.882.445
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C537730	Oculocutaneous albinism type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111423 (SELECTIVITY GROUP), CHEMBL3795 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,841 (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
CHEMBL2070241	BREMELANOTIDE	4	157
CHEMBL3301624	SETMELANOTIDE	4	679
CHEMBL441738	AFAMELANOTIDE	4	602
CHEMBL214332	INTERMEDINE	2	2,391
CHEMBL3977876	PL-8177	2	12
CHEMBL4802244	DERSIMELAGON PHOSPHATE	1

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2228478	Efficacy	3	desipramine	Major Depressive Disorder
rs2228479	Efficacy	3	desipramine	Major Depressive Disorder

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1805007	MC1R		0.00	0
rs1805008	MC1R		0.00	0
rs2228478	MC1R, TUBB3	3	2.25	1	desipramine
rs2228479	MC1R	3	2.25	1	desipramine

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
afamelanotide	Full agonist	10.0	pIC50
[125I]NDP-MSH	Full agonist	9.5	pKd
MT-II	Full agonist	9.4	pIC50
SHU9119	Partial agonist	9.2	pKd
MS05	Full agonist	9.1	pKd
ACTH	Agonist	8.6	pKi
agouti	Inverse agonist	8.6	pKd
setmelanotide	Agonist	8.41	pKi
α-MSH	Full agonist	8.4	pIC50
bremelanotide	Agonist	8.19	pKi
ASIP [90-132 (L89Y)]	Inverse agonist	8.1	pIC50
HS024	Antagonist	7.7	pKd
HS014	Partial agonist	7.0	pKd

Binding affinities (BindingDB)

258 measured of 261 human assays (261 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(2,4-dichlorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.055 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(3,4-dichlorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.055 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-5-[(4-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.08 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,18S)-18-[[(2S)-2-acetamidohexanoyl]amino]-N-[(2R)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-3,6,9,15,19-pentaoxo-1,4,7,10,14-pentazacyclononadecane-11-carboxamide	KI	0.095 nM	US-9447148: Melanocortin-1 receptor-specific cyclic peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-5-[(4-methylphenyl)methyl]-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.145 nM	US-9040663: Melanocortin receptor-specific peptides
CAS_75921-69-6	KI	0.224 nM
alpha-MSH, [Nle4, D-Phe7]	KI	0.224 nM
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(4-fluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.25 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-5-[(4-methoxyphenyl)methyl]-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.25 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-8-[3-(diaminomethylideneamino)propyl]-5-[(3,4-difluorophenyl)methyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.25 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-[(2-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-2-(phenylmethoxymethyl)-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-[(2-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-2-[(1R)-1-phenylmethoxyethyl]-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.35 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-5-[[2-(trifluoromethyl)phenyl]methyl]-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.6 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-[(3-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.6 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-[(4-cyanophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.6 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-8-[3-(diaminomethylideneamino)propyl]-5-[(4-fluorophenyl)methyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.65 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(2-fluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.7 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-5-[(3-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.75 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,18S)-18-[[(2S)-2-acetamidohexanoyl]amino]-N-[(2S)-1-amino-3-naphthalen-1-yl-1-oxopropan-2-yl]-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-3,6,9,15,19-pentaoxo-1,4,7,10,14-pentazacyclononadecane-11-carboxamide	KI	0.75 nM	US-9447148: Melanocortin-1 receptor-specific cyclic peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-5-[(4-cyanophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.833 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-5-[[3-(trifluoromethyl)phenyl]methyl]-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.95 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-8-[3-(diaminomethylideneamino)propyl]-5-[(2-fluorophenyl)methyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	0.95 nM	US-9040663: Melanocortin receptor-specific peptides
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-20-[(2-chlorophenyl)methyl]-17-[3-(diaminomethylideneamino)propyl]-25-hydroxy-14-(1H-indol-3-ylmethyl)-2,6,13,16,19,22-hexaoxo-1,7,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	KI	1 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2R)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-[(2-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	1 nM	US-9040663: Melanocortin receptor-specific peptides
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-17-[3-(diaminomethylideneamino)propyl]-20-[(4-fluorophenyl)methyl]-25-hydroxy-14-(1H-indol-3-ylmethyl)-2,6,13,16,19,22-hexaoxo-1,7,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	KI	1 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(3-fluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	2 nM	US-9040663: Melanocortin receptor-specific peptides
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-20-[(3-chlorophenyl)methyl]-17-[3-(diaminomethylideneamino)propyl]-25-hydroxy-14-(1H-indol-3-ylmethyl)-2,6,13,16,19,22-hexaoxo-1,7,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	KI	2 nM	US-9040663: Melanocortin receptor-specific peptides
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-20-[(4-cyanophenyl)methyl]-17-[3-(diaminomethylideneamino)propyl]-25-hydroxy-14-(1H-indol-3-ylmethyl)-2,6,13,16,19,22-hexaoxo-1,7,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	KI	2 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-8-[3-(diaminomethylideneamino)propyl]-5-[(4-fluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-2-(2-methylsulfonylethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	2 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,18S)-18-[[(2S)-2-acetamidohexanoyl]amino]-N-[(2R)-1-amino-3-naphthalen-1-yl-1-oxopropan-2-yl]-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-3,6,9,15,19-pentaoxo-1,4,7,10,14-pentazacyclononadecane-11-carboxamide	KI	2 nM	US-9447148: Melanocortin-1 receptor-specific cyclic peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-aminoethyl)-5-[(2-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(3-amino-3-oxopropyl)-5-[(3-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-5-[(4-cyanophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-2-methyl-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(3S,11S,14S,17S,20R,23S,25R)-3-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-17-[3-(diaminomethylideneamino)propyl]-20-[(2-fluorophenyl)methyl]-25-hydroxy-14-(1H-indol-3-ylmethyl)-2,6,13,16,19,22-hexaoxo-1,7,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(4-fluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(4-fluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-8-[3-(diaminomethylideneamino)propyl]-5-[(3,4-difluorophenyl)methyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	3 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,18S)-18-[[(2S)-2-acetamidohexanoyl]amino]-N-[(2S)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-2-(1H-imidazol-5-ylmethyl)-3,6,9,15,19-pentaoxo-1,4,7,10,14-pentazacyclononadecane-11-carboxamide	KI	3 nM	US-9447148: Melanocortin-1 receptor-specific cyclic peptides
desacetyl-alpha-MSH	KI	3.68 nM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-12-(3-amino-3-oxopropyl)-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,19-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	KI	4 nM	US-9458201: Melanocortin receptor-specific heptapeptides
(3S,11S,14S,17S,20R,23S)-3-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-20-[(4-cyanophenyl)methyl]-17-[3-(diaminomethylideneamino)propyl]-14-(1H-indol-3-ylmethyl)-2,6,13,16,19,22-hexaoxo-1,7,12,15,18,21-hexazabicyclo[21.3.0]hexacosane-11-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(3-amino-3-oxopropyl)-5-[(4-cyanophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(aminomethyl)-5-[(3-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-5-[(3-methylphenyl)methyl]-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-5-[(2-methylphenyl)methyl]-3,6,9,12,19,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(3-amino-3-oxopropyl)-5-[(2-chlorophenyl)methyl]-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(3-amino-3-oxopropyl)-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-5-[[2-(trifluoromethyl)phenyl]methyl]-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	4 nM	US-9040663: Melanocortin receptor-specific peptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(3-amino-3-oxopropyl)-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,17,23-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-14-carboxamide	KI	5 nM	US-9458201: Melanocortin receptor-specific heptapeptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-11-(1H-indol-3-ylmethyl)-3,6,9,12,16,23-hexaoxo-1,4,7,10,13,17-hexazacyclotricosane-14-carboxamide	KI	5 nM	US-9458201: Melanocortin receptor-specific heptapeptides
(2S,5R,8S,11S,14S,22S)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-2-(2-amino-2-oxoethyl)-5-benzyl-8-[3-(diaminomethylideneamino)propyl]-11-(naphthalen-2-ylmethyl)-3,6,9,12,16,23-hexaoxo-1,4,7,10,13,17-hexazacyclotricosane-14-carboxamide	KI	5 nM	US-9458201: Melanocortin receptor-specific heptapeptides

ChEMBL bioactivities

1644 potent at pChembl≥5 of 1694 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL3972160
11.00	Ki	0.01	nM	CHEMBL3975096
11.00	Ki	0.01	nM	CHEMBL3920516
11.00	Ki	0.01	nM	CHEMBL3928766
11.00	EC50	0.01	nM	CHEMBL3898758
11.00	IC50	0.01	nM	CHEMBL4093140
11.00	EC50	0.01	nM	CHEMBL4093140
11.00	EC50	0.01	nM	CHEMBL569693
10.92	Ki	0.012	nM	CHEMBL3964400
10.92	EC50	0.012	nM	CHEMBL3958741
10.85	Ki	0.014	nM	CHEMBL3956787
10.85	EC50	0.014	nM	CHEMBL3922906
10.82	Ki	0.015	nM	CHEMBL3946641
10.82	Ki	0.015	nM	CHEMBL3930415
10.82	Ki	0.015	nM	CHEMBL3972716
10.82	EC50	0.015	nM	CHEMBL3936714
10.80	EC50	0.016	nM	CHEMBL3896173
10.80	EC50	0.016	nM	CHEMBL428615
10.70	Ki	0.02	nM	CHEMBL3904232
10.70	EC50	0.02	nM	CHEMBL2114259
10.64	EC50	0.023	nM	AFAMELANOTIDE
10.62	EC50	0.024	nM	INTERMEDINE
10.60	Ki	0.025	nM	CHEMBL3922330
10.60	Ki	0.025	nM	CHEMBL3981581
10.60	Ki	0.025	nM	CHEMBL3949338
10.60	EC50	0.025	nM	CHEMBL3966176
10.60	EC50	0.025	nM	CHEMBL3891338
10.52	Ki	0.03	nM	CHEMBL3938542
10.52	Ki	0.03	nM	CHEMBL3917089
10.51	EC50	0.031	nM	CHEMBL3911582
10.44	EC50	0.036	nM	CHEMBL2096742
10.44	EC50	0.036	nM	CHEMBL266417
10.40	Ki	0.04	nM	PL-8177
10.40	Ki	0.04	nM	CHEMBL3968105
10.40	Ki	0.04	nM	CHEMBL3955172
10.35	EC50	0.045	nM	CHEMBL377465
10.35	EC50	0.04467	nM	CHEMBL5191309
10.34	Ki	0.046	nM	AFAMELANOTIDE
10.33	EC50	0.04677	nM	CHEMBL5185775
10.30	EC50	0.05	nM	CHEMBL266665
10.30	Ki	0.05	nM	CHEMBL3901634
10.30	Kd	0.05012	nM	CHEMBL428801
10.28	EC50	0.052	nM	CHEMBL3986527
10.26	EC50	0.055	nM	CHEMBL440801
10.26	EC50	0.055	nM	CHEMBL428801
10.25	EC50	0.05623	nM	CHEMBL5083551
10.24	Ki	0.05754	nM	CHEMBL5185945
10.22	EC50	0.06	nM	CHEMBL3350329
10.22	EC50	0.06	nM	CHEMBL3350330
10.20	EC50	0.0631	nM	MELATONAN

PubChem BioAssay actives

1327 with measured affinity, of 2618 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
(2S)-2-acetamido-N-[(2R)-1-[(2S,4S)-2-[3-(diaminomethylideneamino)propyl]-4-(naphthalen-2-ylmethoxy)pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-3-(1H-imidazol-5-yl)propanamide	268363: Agonist activity at human MC1R transfected in HEK293 cells	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]-4-methylsulfanylbutanoyl]amino]-5-[[(2S)-1-[[(2R,3S)-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-phenylbutan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	71942: Decrease in frog skin reflectivity (metabotropic activity).	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-5-yl)-1-oxopropan-2-yl]amino]pentanoic acid	1476992: Displacement of [125I]-NDP-alpha-MSH from human MC1R expressed in HEK293 cells after 40 mins by gamma counting method	ic50	<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	108605: Effective concentration required for the biological activity against human Melanocortin 1 receptor	ec50	<0.0001	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	1852334: Displacement of [125I]-NDP-alpha-MSH from human MC1R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay	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	1852337: Agonist activity at human MC1R 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	1852337: Agonist activity at human MC1R 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)-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	1852337: Agonist activity at human MC1R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	<0.0001	uM
(2S)-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-(4-phenylbutanoylamino)propanoyl]amino]-3-phenylpropanoyl]amino]pentanamide	108622: Binding affinity towards human Melanocortin 1 receptor (hMC1R)	ki	<0.0001	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	108606: Evaluated for agonist activity against human Melanocortin 1 receptor using hMC1-R assay	ec50	<0.0001	uM
(3R,6S,9R,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	108606: Evaluated for agonist activity against human Melanocortin 1 receptor using hMC1-R 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	108606: Evaluated for agonist activity against human Melanocortin 1 receptor using hMC1-R assay	ec50	<0.0001	uM
(2S)-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-(4-phenylbutanoylamino)propanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]pentanamide	246073: Agonistic activity against human Melanocortin 1 receptor	ec50	<0.0001	uM
(2S)-N-[(2R)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-[[(2R)-3-phenyl-2-[[(2S)-2-(4-phenylbutanoylamino)-3-(3H-pyrrol-4-yl)propanoyl]amino]propanoyl]amino]pentanamide	447389: Agonistic activity against human MC1R	ec50	<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	108605: Effective concentration required for the biological activity against human Melanocortin 1 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]-4-methylsulfanylbutanoyl]amino]-5-[[(2S)-1-[[(2S,3R)-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-phenylbutan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	71942: Decrease in frog skin reflectivity (metabotropic activity).	ec50	<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	1480172: Agonist activity at human MC1R expressed in low doxycyclin-treated HEK293 cell membranes assessed as increase in cAMP production after 45 mins by HTRF method	ec50	<0.0001	uM
(3R,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-[(1R)-1-(1H-indol-3-yl)ethyl]-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	71942: Decrease in frog skin reflectivity (metabotropic activity).	ec50	0.0001	uM
(3R,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-[(1S)-1-(1H-indol-3-yl)ethyl]-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	108474: Effective concentration for the effect of Melanocortin 1 receptor in the frog skin.	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]-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	108474: Effective concentration for the effect of Melanocortin 1 receptor in the frog skin.	ec50	0.0001	uM
3-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-31,37-bis(3-carbamimidamidopropyl)-25-[(1R)-1-hydroxyethyl]-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-35,38-dimethyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-16-yl]propanoic acid	1812557: Agonist activity at human melanocortin receptor 1 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
1-[3-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16,31-bis(3-carbamimidamidopropyl)-25-[(1R)-1-hydroxyethyl]-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-37-yl]propyl]guanidine	1812557: Agonist activity at human melanocortin receptor 1 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
1-[3-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16,31-bis(3-carbamimidamidopropyl)-25-[(1R)-1-hydroxyethyl]-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-17-methyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-37-yl]propyl]guanidine	1812557: Agonist activity at human melanocortin receptor 1 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
1-[3-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16-(3-carbamimidamidopropyl)-25-[(1R)-1-hydroxyethyl]-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-17,31-dimethyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-37-yl]propyl]guanidine	1812557: Agonist activity at human melanocortin receptor 1 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
1-[3-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16,31-bis(3-carbamimidamidopropyl)-25-[(1R)-1-hydroxyethyl]-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-17,35,38-trimethyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-37-yl]propyl]guanidine	1812557: Agonist activity at human melanocortin receptor 1 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
1-[3-[(1R,4S,7S,10S,13S,16R,19S,22S,25R,28S,31S,34S,37R,40S)-16,37-dibenzyl-4-[(2S)-butan-2-yl]-13-(3-carbamimidamidopropyl)-22-[(1R)-1-hydroxyethyl]-19,40-bis(1H-imidazol-4-ylmethyl)-10,31-bis(1H-indol-3-ylmethyl)-7,14,28-trimethyl-3,6,9,12,15,18,21,24,27,30,33,36,39,42-tetradecaoxo-44,45-dithia-2,5,8,11,14,17,20,23,26,29,32,35,38,41-tetradecazabicyclo[23.17.4]hexatetracontan-34-yl]propyl]guanidine	1812557: Agonist activity at human melanocortin receptor 1 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
2-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16,37-bis(3-carbamimidamidopropyl)-31-[(4-hydroxyphenyl)methyl]-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-17,35,38-trimethyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-25-yl]acetic acid	1812557: Agonist activity at human melanocortin receptor 1 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
3-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16,31,37-tris(3-carbamimidamidopropyl)-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-17,35,38-trimethyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-25-yl]propanoic acid	1812557: Agonist activity at human melanocortin receptor 1 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
2-[(1R,4S,7S,13S,16S,19R,22S,25S,28R,31S,34S,37S,40R,43S)-19,40-dibenzyl-4-[(2S)-butan-2-yl]-16,31,37-tris(3-carbamimidamidopropyl)-22,43-bis(1H-imidazol-4-ylmethyl)-13,34-bis(1H-indol-3-ylmethyl)-17,35,38-trimethyl-3,6,12,15,18,21,24,27,30,33,36,39,42,45-tetradecaoxo-47,48-dithia-2,5,11,14,17,20,23,26,29,32,35,38,41,44-tetradecazatricyclo[26.17.4.07,11]nonatetracontan-25-yl]acetic acid	1812557: Agonist activity at human melanocortin receptor 1 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
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	1852337: Agonist activity at human MC1R 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)-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	1852337: Agonist activity at human MC1R 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)-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	1852337: Agonist activity at human MC1R 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)-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	1852337: Agonist activity at human MC1R 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)-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	1852337: Agonist activity at human MC1R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0001	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	1852337: Agonist activity at human MC1R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay	ec50	0.0001	uM
(3S,11S,17S,20S,23R,26S,28R)-3-[[(2S)-2-acetamidohexanoyl]amino]-28-[3-(diaminomethylideneamino)propanoylamino]-20-[3-(diaminomethylideneamino)propyl]-17-(1H-indol-3-ylmethyl)-23-(naphthalen-2-ylmethyl)-2,5,13,16,19,22,25-heptaoxo-1,6,12,15,18,21,24-heptazabicyclo[24.3.0]nonacosane-11-carboxamide	2089627: Partial agonist activity at C-terminal HA-tagged human MC1-R stably expressed in HEK293 cells co-expressing GScAMP22P cAMP reporter assessed as inhibition of alpha-MSH induced cAMP production by cell based luminescence assay	ic50	0.0001	uM
(3S,11S,17S,20S,23R,26S,28S)-3-[[(2S)-2-acetamidohexanoyl]amino]-28-[3-(diaminomethylideneamino)propanoylamino]-20-[3-(diaminomethylideneamino)propyl]-17-(1H-indol-3-ylmethyl)-23-(naphthalen-2-ylmethyl)-2,5,13,16,19,22,25-heptaoxo-1,6,12,15,18,21,24-heptazabicyclo[24.3.0]nonacosane-11-carboxamide	2089627: Partial agonist activity at C-terminal HA-tagged human MC1-R stably expressed in HEK293 cells co-expressing GScAMP22P cAMP reporter assessed as inhibition of alpha-MSH induced cAMP production by cell based luminescence assay	ic50	0.0001	uM
(3R,6S,9R,12S,15S,23R)-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-15-[[(2S)-2-amino-3-phenylpropanoyl]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	108475: Effective concentration required for maximum agonist response at melanocortin 1 receptor from frog skin.	ec50	0.0001	uM
(4S,7R,10S,13R,16R,19R)-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2R)-2-amino-3-phenylpropanoyl]amino]-13-benzyl-10-[3-(diaminomethylideneamino)propyl]-16-(1H-imidazol-5-ylmethyl)-7-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	108475: Effective concentration required for maximum agonist response at melanocortin 1 receptor from frog skin.	ec50	0.0001	uM
(3R,6S,9R,12S,15S,23R)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-9-[(4-iodophenyl)methyl]-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	108606: Evaluated for agonist activity against human Melanocortin 1 receptor using hMC1-R assay	ec50	0.0001	uM
(3S,6R,9R,12R,15R,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-9-[(4-iodophenyl)methyl]-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	108605: Effective concentration required for the biological activity against human Melanocortin 1 receptor	ec50	0.0001	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	246073: Agonistic activity against human Melanocortin 1 receptor	ec50	0.0001	uM
(2S)-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-[(5-oxo-5-phenylpentanoyl)amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]pentanamide	246073: Agonistic activity against human Melanocortin 1 receptor	ec50	0.0001	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	239511: Inhibition of [125I]NDP-alpha-MSH binding to melanocortin-1 receptor expressed in HEK293 cells	ki	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	239511: Inhibition of [125I]NDP-alpha-MSH binding to melanocortin-1 receptor expressed in HEK293 cells	ki	0.0001	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	270598: Agonist activity at human MC1R	ec50	0.0001	uM
(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[[(2R)-2-[[(2S)-2-(butanoylamino)-3-(1H-imidazol-5-yl)propanoyl]amino]-3-(4-ethoxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanamide	108602: Effective concentration against hMC1R using HEK293 cells was determined by measuring the cAMP accumulation	ec50	0.0001	uM
(3S,6S,9S,12R,15S,18S,26S)-18-[[(2S)-2-acetamidohexanoyl]amino]-12-benzyl-9-[3-(diaminomethylideneamino)propyl]-15-(1H-imidazol-5-ylmethyl)-6-(1H-indol-3-ylmethyl)-3-methyl-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,21-heptazacyclohexacosane-26-carboxamide	108604: Effective concentration for intracellular cAMP accumulation in L-cells expressing Melanocortin 1 receptor	ec50	0.0001	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	1907764: Antagonist activity at human MC1R transfected in HEK293 cells co-transfected with GScAMP22F assessed as decrease in alpha-MSH induced cAMP level in presence of 10 nM alpha-MSH by split luciferase cAMP sensor dynamic assay	ic50	0.0001	uM
(3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(4H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide	473155: Agonist activity at human recombinant MC1 receptor expressed in HEK293 cells assessed as cAMP accumulation by enzyme fragment complementation assay	ec50	0.0001	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
Particulate Matter	decreases expression, increases abundance	3
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
quercitrin	increases expression	1
cobaltous chloride	decreases expression	1
indole	affects binding	1
naphthalene	affects binding	1
hydroquinone	decreases expression	1
puerarin	decreases expression	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pifithrin	decreases expression	1
pomiferin	decreases expression	1
osajin	decreases expression	1
ICG 001	increases expression	1
rosavin	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Chlorogenic Acid	increases expression	1
Clozapine	increases expression	1
Dimethyl Sulfoxide	affects expression	1
Propolis	decreases expression	1
Rotenone	decreases expression	1

ChEMBL screening assays

319 unique, capped per target: 164 functional, 155 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL824638	Binding	Selectivity as ratio of binding affinity for human melanocortin 1 and melanocortin 4 receptors	Novel cyclic templates of alpha-MSH give highly selective and potent antagonists/agonists for human melanocortin-3/4 receptors. — J Med Chem
CHEMBL868540	Functional	Selectivity for human MC4R over MC1R	Design of cyclic peptides with agonist activity at melanocortin receptor-4. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 3 cancer cell line, 3 transformed cell line, 2 spontaneously immortalized cell line, 2 telomerase immortalized cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2FY	MBA72	Cancer cell line	Male
CVCL_A2FZ	MBA72R	Cancer cell line	Male
CVCL_C0T3	ACTOne MC1R	Transformed cell line	Female
CVCL_KV45	cAMP Hunter CHO-K1 MC1R Gs	Spontaneously immortalized cell line	Female
CVCL_LA67	PathHunter U2OS MC1R beta-arrestin	Cancer cell line	Female
CVCL_T415	Psi-CRIP-MSHR	Transformed cell line	Male
CVCL_VS18	830-c	Finite cell line	Male
CVCL_VS19	Hermes 4A	Telomerase immortalized cell line	Male
CVCL_VS20	Hermes 4B	Telomerase immortalized cell line	Male
CVCL_VS21	Hermes 4C	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00324272	PHASE4	COMPLETED	Post-Operative Drainage Following Lymph Node Dissection
NCT01053819	PHASE4	COMPLETED	Can We Miss Pigmented Lesions in Psoriasis Patients?
NCT01898585	PHASE4	COMPLETED	An Open-Label Study of Zelboraf (Vemurafenib) in Patients With Braf V600 Mutation Positive Metastatic Melanoma
NCT02068196	PHASE4	ACTIVE_NOT_RECRUITING	A National Phase IV Study With Ipilimumab for Patients With Advanced Malignant Melanoma.
NCT02451488	PHASE4	COMPLETED	Neoadjuvant Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Cutaneous Stage L-lll Melanoma
NCT03313544	PHASE4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03340506	PHASE4	RECRUITING	Dabrafenib and/or Trametinib Rollover Study
NCT03715205	PHASE4	COMPLETED	Study to Evaluate the Safety of Pembrolizumab in Participants With Unresectable or Metastatic Melanoma or Non-small Cell Lung Cancer in India (MK-3475-593/KEYNOTE-593)
NCT04261179	PHASE4	UNKNOWN	Study Comparing Lymphoseek® vs. Albumin Nanocolloid in Head and Neck, Melanoma and Breast Cancer
NCT05467137	PHASE4	UNKNOWN	Sentinel Lymph Node Detection in Patients With Stage Ib-III Melanoma Using MSOT and ICG
NCT06116461	PHASE4	UNKNOWN	Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response
NCT06785974	PHASE4	NOT_YET_RECRUITING	Statins to Prevent Immune Checkpoint Inhibitor-induced PRogression of AtherosLerosis
NCT07004335	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Iparomlimab and Tuvonralimab Injection in Combination With Bevacizumab After Progression on Anti-PD-(L)1 Therapy in Advanced Melanoma: A Prospective, Single-Arm, Exploratory Clinical Study
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT07445022	PHASE4	RECRUITING	RWS of Tunlametinib in NRAS-Mutant Advanced Melanoma
NCT07504796	PHASE4	RECRUITING	ctDNA-guided Addition of Ipilimumab to Patients Receiving Nivolumab and Relatlimab
NCT07574047	PHASE4	NOT_YET_RECRUITING	MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma.
NCT00001296	PHASE3	COMPLETED	A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion With Melphalan, Tumor Necrosis Factor, and Interferon-Gamma in Patients With Locally Advanced Extremity Melanoma
NCT00002455	PHASE3	UNKNOWN	Immunotherapy After Surgery in Treating Patients With Breast Cancer, Colon Cancer, or Melanoma
NCT00002763	PHASE3	UNKNOWN	High-Dose or Low-Dose Interferon Alfa Compared With No Further Therapy Following Surgery in Treating Patients With Stage III Melanoma
NCT00002767	PHASE3	UNKNOWN	Interferon Alfa With or Without Vaccine Therapy in Treating Patients With Metastatic Melanoma
NCT00002882	PHASE3	COMPLETED	Interferon Alfa With or Without Combination Chemotherapy Plus Interleukin-2 in Treating Patients With Melanoma
NCT00002892	PHASE3	COMPLETED	Interferon Alfa or No Further Therapy Following Surgery in Treating Patients With Stage II, Stage III, or Recurrent Melanoma
NCT00003027	PHASE3	COMPLETED	Combination Chemotherapy With or Without Interleukin-2 and Interferon Alfa in Treating Patients With Metastatic Melanoma
NCT00003444	PHASE3	COMPLETED	Interferon Alfa-2b With or Without Radiation Therapy in Treating Patients With Melanoma That Has Metastasized to Lymph Nodes in the Neck, Under the Arm, or in the Groin
NCT00003641	PHASE3	ACTIVE_NOT_RECRUITING	High-Dose Interferon Alfa in Treating Patients With Stage II or Stage III Melanoma
NCT00003647	PHASE3	COMPLETED	Chemotherapy With or Without Immunotherapy in Treating Patients With Stage III or Stage IV Melanoma
NCT00003789	PHASE3	COMPLETED	Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Locally Advanced Melanoma of the Arm or Leg
NCT00004196	PHASE3	COMPLETED	Interferon Alfa-2b in Treating Patients With Melanoma and Early Lymph Node Metastasis
NCT00005052	PHASE3	UNKNOWN	Vaccine Therapy in Treating Patients With Primary Stage II Melanoma
NCT00006237	PHASE3	COMPLETED	S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma
NCT00006249	PHASE3	UNKNOWN	Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma
NCT00016263	PHASE3	COMPLETED	Dacarbazine With or Without Oblimersen (G3139) in Treating Patients With Advanced Malignant Melanoma
NCT00019682	PHASE3	COMPLETED	Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
NCT00020839	PHASE3	TERMINATED	Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain
NCT00039000	PHASE3	COMPLETED	Study of Heat Shock Protein-Peptide Complex (HSPPC-96) Versus IL-2/DTIC for Stage IV Melanoma
NCT00039234	PHASE3	UNKNOWN	Interleukin-2 With or Without Histamine Dihydrochloride in Treating Patients With Stage IV Melanoma Metastatic to the Liver
NCT00052130	PHASE3	UNKNOWN	Vaccine Therapy for Patients With Stage III Melanoma
NCT00052156	PHASE3	UNKNOWN	Vaccine Therapy for Patients With Stage IV Melanoma
NCT00057616	PHASE3	COMPLETED	Study to Compare the Efficacy and Safety of CC-5013 vs. Placebo in Subjects With Metastatic Malignant Melanoma.