MCHR1

Summary

MCHR1 (melanin concentrating hormone receptor 1, HGNC:4479) is a protein-coding gene on chromosome 22q13.2, encoding Melanin-concentrating hormone receptor 1 (Q99705). Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.

The protein encoded by this gene, a member of the G protein-coupled receptor family 1, is an integral plasma membrane protein which binds melanin-concentrating hormone. The encoded protein can inhibit cAMP accumulation and stimulate intracellular calcium flux, and is probably involved in the neuronal regulation of food consumption. Although structurally similar to somatostatin receptors, this protein does not seem to bind somatostatin.

Source: NCBI Gene 2847 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 100 total
• Druggable target: yes
• MANE Select transcript: NM_005297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4479
Approved symbol	MCHR1
Name	melanin concentrating hormone receptor 1
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	SLC1, MCH1R
Ensembl gene	ENSG00000128285
Ensembl biotype	protein_coding
OMIM	601751
Entrez	2847

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000249016, ENST00000381433, ENST00000465662, ENST00000498400

RefSeq mRNA: 1 — MANE Select: NM_005297 NM_005297

CCDS: CCDS14004

Canonical transcript exons

ENST00000249016 — 2 exons

Exon	Start	End
ENSE00000880414	40680949	40682812
ENSE00001826977	40679484	40679734

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 91.52.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6446 / max 41.7655, expressed in 272 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192428	0.5955	260
192427	0.0491	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	91.52	gold quality
middle temporal gyrus	UBERON:0002771	89.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.64	gold quality
prefrontal cortex	UBERON:0000451	81.41	gold quality
superior frontal gyrus	UBERON:0002661	80.55	gold quality
entorhinal cortex	UBERON:0002728	79.29	gold quality
postcentral gyrus	UBERON:0002581	78.48	gold quality
frontal cortex	UBERON:0001870	78.21	gold quality
primary visual cortex	UBERON:0002436	78.08	gold quality
parietal lobe	UBERON:0001872	77.39	gold quality
neocortex	UBERON:0001950	76.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.72	gold quality
occipital lobe	UBERON:0002021	74.49	gold quality
anterior cingulate cortex	UBERON:0009835	74.22	gold quality
cerebral cortex	UBERON:0000956	74.03	gold quality
right frontal lobe	UBERON:0002810	74.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	73.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.36	gold quality
right uterine tube	UBERON:0001302	72.65	gold quality
temporal lobe	UBERON:0001871	69.91	gold quality
hypothalamus	UBERON:0001898	69.64	gold quality
Ammon’s horn	UBERON:0001954	67.22	gold quality
telencephalon	UBERON:0001893	66.96	gold quality
right ovary	UBERON:0002118	66.88	gold quality
forebrain	UBERON:0001890	66.50	gold quality
islet of Langerhans	UBERON:0000006	65.90	gold quality
smooth muscle tissue	UBERON:0001135	65.80	gold quality
cartilage tissue	UBERON:0002418	65.78	gold quality
body of uterus	UBERON:0009853	65.41	gold quality
cerebellar vermis	UBERON:0004720	64.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting MCHR1, 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-548P	99.98	72.25	3784
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-324-5P	95.68	65.20	560
HSA-MIR-6846-3P	94.80	65.19	389
HSA-MIR-4783-3P	73.56	61.87	82

Literature-anchored findings (GeneRIF, showing 25)

• The 10-amino-acid cyclic core of the hMCH neuropeptide with the Arg attached to the N-terminus of the disulfide ring is sufficient for full activation of melanin-concentrating hormone receptor 1. (PMID:11478907)
• Synthesis and biological evaluation in vitro of a selective, high potency peptide agonist of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1. (PMID:11839762)
• MCH1 and MCH2 receptors were investigated and are different from those in SVK14 cells. (PMID:12127971)
• MCHR1 is expressed and functional in human skin (PMID:12176038)
• MCHR1 receptor expression on most cell types can trigger, in the presence of MCH, cAMP synthesis and calcium mobilization in peripheral blood mononuclear cells (PBMCs). Moreover, MCH treatment decreases the CD3-stimulated PBMC proliferation in vitro. (PMID:12220661)
• study demonstrates a complex interaction between melanin concentrating hormone receptor 1 and Gs protein-coupled signaling pathways (PMID:12865333)
• multiple antibody binding sites on melanin-concentrating hormone receptor 1 in vitiligo, including regions between amino acids 1 to 138 and 139 to 298. (PMID:14632194)
• Periplakin interferes with G protein activation by the melanin-concentrating hormone receptor-1 by binding to the proximal segment of the receptor C-terminal tail (PMID:15590649)
• a single point mutation at position 255 (T255A), which is located at the junction of intracellular loop 3 and transmembrane domain 6, reduces the MCHR1 cell surface expression level to 20% of that observed for the wild-type receptor (PMID:15928315)
• Association of MCHR1 alleles/haplotype detected might be related to juvenile-onset obesity, conditional on a particular genetic and/or environmental background. (PMID:15941924)
• Our results suggest that MIZIP might play an important role in mammalian cells by associating with tubulin and thus might provide a link between MCHR1 and tubulin functions. (PMID:16039987)
• study suggests that severe forms of obesity with early onset may be associated with single nucleotide polymorphisms in melanin-concentrating hormone receptor 1 (MCHR1) (PMID:16186414)
• Study suggest that GPR24 variants may confer susceptibility to both bipolar affective disorder and schizophrenia. (PMID:16741940)
• Single nucleotide polymorphisms of MCHR1 did not have effects on metabolic variables in humans. (PMID:18198296)
• These data suggest that a functional interaction between MCHR1 and caveolin-1 in lipid rafts exists and provide a basis for further biochemical studies to understand the significance on MCH-mediated signal transduction events. (PMID:18722347)
• analysis of epitope specificity of MCHR1 antibodies (PMID:19320743)
• data suggest that RGS2 and RGS8 differentially associate with MCHR1 and may represent two distinct modes of signaling mechanisms in vivo (PMID:20633139)
• two loss-of-function mutants were identified in markedly underweight individuals, raising the possibility that a lean phenotype may be linked to deficient MCHR1 signaling (PMID:20833795)
• MCHR1 expression level was 1.6 times higher in vitiligo uninvolved skin (P < 0.05) and 2.23 times lower in involved skin (P < 0.05), when compared to healthy control skin. (PMID:20888736)
• DNA methylation at MCHR1 is allele-specific, age-dependent, body mass index-associated and affects transcription. (PMID:21637341)
• results suggest that MCHR1 may influence schizophrenia susceptibility, in particular among men and patients responding to conventional (nonclozapine) treatment (PMID:22081064)
• SLC-1 protein human mutation demonstrated important genetic susceptibility of sporadic nonsyndromic hearing loss in China. (PMID:22154049)
• Polymorphisms in the MCHR1 gene are associated with differences in body composition and interact with physiologic and energy-related lifestyle factors. (PMID:24305679)
• Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating. (PMID:31563948)
• PDGF Promotes Dermal Fibroblast Activation via a Novel Mechanism Mediated by Signaling Through MCHR1. (PMID:34912333)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mchr1b	ENSDARG00000022525
danio_rerio	mchr1a	ENSDARG00000104093
mus_musculus	Mchr1	ENSMUSG00000050164
rattus_norvegicus	Mchr1	ENSRNOG00000018895

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), PROKR1 (ENSG00000169618), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR88 (ENSG00000181656), GPR19 (ENSG00000183150), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

Melanin-concentrating hormone receptor 1 — Q99705 (reviewed: Q99705)

Alternative names: G-protein coupled receptor 24, MCH-1R, SLC-1, Somatostatin receptor-like protein

All UniProt accessions (2): Q99705, A6ZJ87

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.

Subunit / interactions. Interacts with NCDN.

Subcellular location. Cell membrane.

Tissue specificity. Highest level in brain, particularly in the frontal cortex and hypothalamus, lower levels in the liver and heart.

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

RefSeq proteins (1): NP_005288* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004047	MCHR1	Family
IPR008361	MCH_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (49 total): helix 12, topological domain 8, transmembrane region 7, sequence variant 7, strand 7, glycosylation site 3, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8WWK	ELECTRON MICROSCOPY	2.61
8WWN	ELECTRON MICROSCOPY	2.65
8WWL	ELECTRON MICROSCOPY	2.78
8WWM	ELECTRON MICROSCOPY	2.81
8WWH	ELECTRON MICROSCOPY	2.84
8WSS	ELECTRON MICROSCOPY	3.01
8WWJ	ELECTRON MICROSCOPY	3.03
8YNS	ELECTRON MICROSCOPY	3.33
8WWI	ELECTRON MICROSCOPY	3.43
8YNT	ELECTRON MICROSCOPY	3.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99705-F1	85.23	0.65

Antibody-complex structures (SAbDab): 8 — 8WSS, 8WWH, 8WWI, 8WWJ, 8WWK, 8WWL, 8WWM, 8WWN

Functional residue map

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

Disulfide bonds (1): 116–194

Glycosylation sites (3): 13, 16, 23

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-5620922	BBSome-mediated cargo-targeting to cilium
R-HSA-162582	Signal Transduction
R-HSA-1852241	Organelle biogenesis and maintenance
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-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane

MSigDB gene sets: 95 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BEHAVIOR, GCANCTGNY_MYOD_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, TGACATY_UNKNOWN, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, AACTTT_UNKNOWN, AFFAR_YY1_TARGETS_DN

GO Biological Process (9): generation of precursor metabolites and energy (GO:0006091), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), positive regulation of cytosolic calcium ion concentration (GO:0007204), neuropeptide signaling pathway (GO:0007218), feeding behavior (GO:0007631), positive regulation of calcium ion transport (GO:0051928), signal transduction (GO:0007165)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), signaling receptor binding (GO:0005102), neuropeptide receptor activity (GO:0008188), melanin-concentrating hormone receptor activity (GO:0030273), hormone binding (GO:0042562), neuropeptide binding (GO:0042923)

GO Cellular Component (6): plasma membrane (GO:0005886), cilium (GO:0005929), neuron projection (GO:0043005), ciliary membrane (GO:0060170), non-motile cilium (GO:0097730), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
Cargo trafficking to the periciliary membrane	1
Signal Transduction	1
GPCR ligand binding	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor activity	2
G protein-coupled receptor signaling pathway	2
plasma membrane bounded cell projection	2
cilium	2
metabolic process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
regulation of biological quality	1
behavior	1
calcium ion transport	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
protein binding	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
protein-hormone receptor activity	1
binding	1
peptide binding	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
cell projection membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCHR1	PMCH	P20382	996
MCHR1	BBS1	Q8NFJ9	828
MCHR1	BBS2	Q9BXC9	792
MCHR1	BBS4	Q96RK4	780
MCHR1	ZMYND19	Q96E35	779
MCHR1	HCRT	O43612	737
MCHR1	TULP3	O75386	722
MCHR1	FAM170A	A1A519	715
MCHR1	POMC	P01189	690
MCHR1	GNAQ	P50148	687
MCHR1	BBS7	Q8IWZ6	671
MCHR1	MC4R	P32245	662
MCHR1	DEAF1	O75398	650
MCHR1	NPY	P01303	640
MCHR1	KCNH2	Q12809	621

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MCHR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
MCHR1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
MCHR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	MCHR1	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	MCHR1	psi-mi:“MI:0915”(physical association)	0.400
HUNK	MCHR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): MCHR1 (Two-hybrid)

ESM2 similar proteins: B0UXR0, E9QJ73, O18982, O97571, O97663, O97666, P21109, P25024, P25025, P32302, P34997, P35343, P35344, P35351, P35374, P35407, P35414, P43142, P49685, P50052, P55919, P55920, P56412, P70612, P97639, Q04683, Q0VDU3, Q1ZY22, Q28003, Q28422, Q28519, Q28807, Q28929, Q2TAD5, Q2YEF9, Q2YEG0, Q2YEG2, Q5IJ49, Q810W6, Q8JZL2

Diamond homologs: A0T2N3, E7F7V7, F1MV99, O08565, O08726, O08858, O35210, O42179, O43603, O77590, O88854, O97666, P25095, P25104, P28646, P29089, P29754, P29755, P30555, P30556, P30680, P30872, P30873, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32300, P32303, P32745, P33533, P33534, P33535, P34975, P34976, P34993, P34994

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MCHR1	“up-regulates activity”	GNAS	binding
MCHR1	“up-regulates activity”	GNAL	binding
MCHR1	“up-regulates activity”	GNAI1	binding
MCHR1	“up-regulates activity”	GNAI3	binding
MCHR1	“up-regulates activity”	GNAO1	binding
MCHR1	“up-regulates activity”	GNAQ	binding
“Melanin-concentrating hormone”	“up-regulates activity”	MCHR1	“chemical activation”
PMCH	up-regulates	MCHR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	16
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

103 predictions. Top by Δscore:

Variant	Effect	Δscore
22:40679732:CAGG:C	donor_loss	1.0000
22:40679733:AGGT:A	donor_loss	1.0000
22:40679734:GGTG:G	donor_loss	1.0000
22:40680944:CCCAG:C	acceptor_loss	1.0000
22:40680945:CCAG:C	acceptor_loss	1.0000
22:40680946:CAGG:C	acceptor_loss	1.0000
22:40680947:A:AG	acceptor_gain	1.0000
22:40680947:A:T	acceptor_loss	1.0000
22:40680947:AG:A	acceptor_gain	1.0000
22:40680948:G:GG	acceptor_gain	1.0000
22:40680948:GG:G	acceptor_gain	1.0000
22:40679730:GGCAG:G	donor_gain	0.9900
22:40679731:GCAG:G	donor_gain	0.9900
22:40679731:GCAGG:G	donor_gain	0.9900
22:40679735:G:GG	donor_gain	0.9900
22:40680948:GGA:G	acceptor_gain	0.9900
22:40680948:GGAT:G	acceptor_gain	0.9900
22:40680948:GGATC:G	acceptor_gain	0.9900
22:40679736:T:G	donor_loss	0.9800
22:40680940:T:A	acceptor_gain	0.9800
22:40679732:CAG:C	donor_gain	0.9600
22:40679733:AG:A	donor_gain	0.9500
22:40679734:GG:G	donor_gain	0.9500
22:40679732:C:T	donor_gain	0.9400
22:40679446:A:AG	donor_gain	0.7800
22:40679733:AGGTG:A	donor_gain	0.7800
22:40679406:TTA:T	donor_gain	0.7500
22:40680304:GCT:G	donor_gain	0.7300
22:40680415:G:GT	donor_gain	0.7300
22:40680492:A:G	donor_gain	0.7200

AlphaMissense

2730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:40681193:G:C	W178C	1.000
22:40681193:G:T	W178C	1.000
22:40681026:G:C	G123R	0.999
22:40681027:G:A	G123D	0.999
22:40681040:C:A	N127K	0.999
22:40681040:C:G	N127K	0.999
22:40681120:T:C	L154P	0.999
22:40681132:A:C	D158A	0.999
22:40681132:A:G	D158G	0.999
22:40681132:A:T	D158V	0.999
22:40681191:T:A	W178R	0.999
22:40681191:T:C	W178R	0.999
22:40681201:G:T	G181V	0.999
22:40681212:T:A	C185S	0.999
22:40681213:G:C	C185S	0.999
22:40681214:C:G	C185W	0.999
22:40681242:A:C	S195R	0.999
22:40681244:T:A	S195R	0.999
22:40681244:T:G	S195R	0.999
22:40681254:A:C	S199R	0.999
22:40681256:C:A	S199R	0.999
22:40681256:C:G	S199R	0.999
22:40681368:T:A	W237R	0.999
22:40681368:T:C	W237R	0.999
22:40681386:A:C	S243R	0.999
22:40681388:C:A	S243R	0.999
22:40681388:C:G	S243R	0.999
22:40681446:T:A	C263S	0.999
22:40681447:G:C	C263S	0.999
22:40681515:T:C	F286L	0.999

dbSNP variants (sampled 300 via entrez): RS1000372408 (22:40677561 G>C), RS1000853506 (22:40681769 T>C), RS1001573811 (22:40678613 C>G), RS1002438503 (22:40682140 T>C), RS1002443300 (22:40682210 G>A), RS1002841790 (22:40678877 C>T), RS1003414079 (22:40683097 G>T), RS1003476661 (22:40683259 G>A,C), RS1003585642 (22:40677624 G>A,C), RS1004222535 (22:40682443 T>C), RS1004759049 (22:40678218 T>C), RS1005317042 (22:40683282 G>A), RS1005422520 (22:40680850 T>A), RS1006644617 (22:40680197 T>C), RS1006937563 (22:40678982 G>A)

Disease associations

OMIM: gene MIM:601751 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004521_42	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004521_55	Autism spectrum disorder or schizophrenia	9.000000e-09
GCST004946_20	Schizophrenia	1.000000e-12
GCST005951_24	Body mass index	2.000000e-08
GCST006940_181	Neurociticism	2.000000e-12
GCST006950_1	Feeling worry	1.000000e-08
GCST007991_7	Large artery stroke	1.000000e-06
GCST008103_42	Bipolar disorder	2.000000e-07
GCST008115_35	Bipolar I disorder	3.000000e-07
GCST010002_83	Refractive error	2.000000e-27

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007660	neuroticism measurement
EFO:0009589	worry measurement
EFO:0009963	bipolar I disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111437 (PROTEIN FAMILY), CHEMBL344 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Melanin-concentrating hormone receptors

Most potent curated ligand interactions (37 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]MCH (human, mouse, rat)	Full agonist	10.8	pKd
melanin-concentrating hormone	Full agonist	10.5	pKi
S36057	Full agonist	10.4	pKi
[Phe13,Tyr19]MCH	Full agonist	10.0	pIC50
S38151	Antagonist	10.0	pKd
Ac-hMCH-(6-16)-NH2	Full agonist	9.9	pIC50
MCH6-17	Full agonist	9.8	pKi
SNAP-7941	Antagonist	9.7	pKd
compound 2 [PMID: 11375253]	Full agonist	9.7	pIC50
MCH (salmon)	Full agonist	9.6	pKi
[125I]S36057	Antagonist	9.5	pKd
compound 17 [PMID: 17125263]	Antagonist	9.4	pIC50
125I-MCH	Antagonist	9.4	pKd
GW803430	Antagonist	9.3	pIC50
[125I][Phe13,Tyr19]MCH	Full agonist	9.2	pKd
tetralin_urea analogue (7o)	Antagonist	9.1	pKi
4-arylphthalazin-1(2H)-3,4-Di-F	Antagonist	9.0	pIC50
MQ1	Negative	8.96	pIC50
C3	Full agonist	8.9	pKi
compound (R)-10h [PMID: 22490048]	Antagonist	8.8	pIC50
7-fluorochromone-2-carboxamide	Antagonist	8.5	pIC50
p-guanidinobenzoyl-MCH-(7-17)	Full agonist	8.4	pIC50
compound 4b [PMID: 19683441]	Antagonist	8.32	pIC50
T-226296	Antagonist	8.3	pIC50
S36541	Antagonist	8.3	pKi

Binding affinities (BindingDB)

827 measured of 828 human assays (830 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
hAc-MCH(6-16)-NH2	KI	0.16 nM
Salmon MCH	KI	0.2 nM
1-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	KI	0.3 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
[Phe13,Tyr19]MCH	KI	0.3 nM
N-Me-Nle8	KI	0.34 nM
N-[(3R)-1-[2-[4-[4-(4-cyclopropylphenoxy)-5-oxo-2H-pyrrol-1-yl]-2-methoxyphenoxy]ethyl]pyrrolidin-3-yl]-2,2,2-trifluoroacetamide	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[4-[2-(3-cyclopropyl-3-hydroxyazetidin-1-yl)ethoxy]-3-methoxyphenyl]-3-(4-cyclopropylphenoxy)pyrrolidin-2-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
tert-butyl N-[1-[2-[4-[4-(4-cyclopropylphenoxy)-5-oxo-2H-pyrrol-1-yl]-2-methoxyphenoxy]ethyl]azetidin-3-yl]carbamate	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[4-[2-(3-cyclopropyl-3-hydroxyazetidin-1-yl)ethoxy]-3-ethylphenyl]-4-(4-cyclopropylphenoxy)-2H-pyrrol-5-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-(difluoromethoxy)-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2H-pyrrol-5-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[4-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[3-methoxy-4-(2-piperidin-1-ylethoxy)phenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[1-(2-pyrrolidin-1-ylethyl)indazol-5-yl]-2H-pyrrol-5-one	KI	0.4 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-1-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-(4-phenylphenoxy)pyrrolidin-2-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-1-[3-ethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-(4-phenylphenoxy)pyrrolidin-2-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-1-[3-methyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-(4-phenylphenoxy)pyrrolidin-2-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-1-[3-chloro-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-(4-phenylphenoxy)pyrrolidin-2-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[4-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-methoxy-4-[2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-methoxy-4-[2-(3-methoxyazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-methoxy-4-[2-(3-methoxy-3-methylazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-(3-hydroxy-3-methylazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[4-[2-(3-hydroxyazetidin-1-yl)ethoxy]-3-methoxyphenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	KI	0.5 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
N-Me-Arg11	KI	0.55 nM
4-(4-cyclopropylphenoxy)-1-[4-[2-[(3R)-3-fluoropyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
tert-butyl N-[1-[2-[4-[4-(4-cyclopropylphenoxy)-5-oxo-2H-pyrrol-1-yl]-2-ethylphenoxy]ethyl]azetidin-3-yl]carbamate	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-(difluoromethoxy)-4-[2-(3-hydroxyazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-(difluoromethoxy)-4-[2-(3-methoxyazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-(difluoromethoxy)-4-[2-(3-hydroxy-3-methylazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[3-bromo-4-[2-(3-hydroxy-3-methylazetidin-1-yl)ethoxy]phenyl]-4-(4-cyclopropylphenoxy)-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-cyclopropyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[1-[2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]ethyl]indazol-5-yl]-2H-pyrrol-5-one	KI	0.6 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[4-[2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[4-[2-(3-hydroxy-3-methylazetidin-1-yl)ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-(3-hydroxyazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-[(3S)-3-hydroxypiperidin-1-yl]ethoxy]phenyl]-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[4-[2-(3-hydroxy-3-methylazetidin-1-yl)ethoxy]-3-methoxyphenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
tert-butyl N-[1-[2-[2-methoxy-4-[5-oxo-4-(4-phenylphenoxy)-2H-pyrrol-1-yl]phenoxy]ethyl]azetidin-3-yl]carbamate	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
1-[3-methoxy-4-[2-(3-methoxyazetidin-1-yl)ethoxy]phenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[1-[2-(2,5-dihydropyrrol-1-yl)ethyl]indazol-5-yl]-2H-pyrrol-5-one	KI	0.7 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-1-[3-chloro-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-(4-cyclopropylphenoxy)pyrrolidin-2-one	KI	0.75 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-3-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-[(3R)-3-methoxypyrrolidin-1-yl]ethoxy]phenyl]pyrrolidin-2-one	KI	0.8 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-1-[4-[2-(azetidin-1-yl)ethoxy]-3-methylphenyl]-3-(4-cyclopropylphenoxy)pyrrolidin-2-one	KI	0.8 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
(3S)-3-(4-cyclopropylphenoxy)-1-[4-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethoxy]-3-methylphenyl]pyrrolidin-2-one	KI	0.8 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[4-[2-[(3S)-3-hydroxypyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.8 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[4-[2-[(3S)-3-fluoropyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.8 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists
4-(4-cyclopropylphenoxy)-1-[4-[2-[2-hydroxyethyl(methyl)amino]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	KI	0.8 nM	US-9499482: Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists

ChEMBL bioactivities

4799 potent at pChembl≥5 of 4914 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.47	Ki	0.034	nM	CHEMBL557629
10.05	IC50	0.09	nM	CHEMBL468099
10.00	IC50	0.1	nM	CHEMBL214322
10.00	IC50	0.1	nM	CHEMBL250516
9.92	IC50	0.12	nM	CHEMBL568571
9.82	IC50	0.15	nM	CHEMBL511542
9.77	Ki	0.17	nM	CHEMBL176219
9.77	IC50	0.17	nM	CHEMBL176219
9.74	Kd	0.18	nM	CHEMBL2146615
9.74	Ki	0.18	nM	CHEMBL538424
9.66	IC50	0.22	nM	CHEMBL566880
9.62	IC50	0.24	nM	CHEMBL555055
9.59	IC50	0.26	nM	CHEMBL582978
9.52	IC50	0.3	nM	CHEMBL412831
9.52	IC50	0.3	nM	CHEMBL439358
9.51	Ki	0.31	nM	CHEMBL176159
9.51	IC50	0.31	nM	CHEMBL176159
9.46	IC50	0.35	nM	CHEMBL582792
9.44	IC50	0.36	nM	CHEMBL2031736
9.44	IC50	0.36	nM	CHEMBL538424
9.44	IC50	0.36	nM	CHEMBL538425
9.41	IC50	0.39	nM	CHEMBL214523
9.41	Ki	0.39	nM	CHEMBL5613278
9.40	IC50	0.4	nM	CHEMBL182261
9.40	Ki	0.4	nM	CHEMBL3618330
9.39	Ki	0.41	nM	CHEMBL178997
9.39	IC50	0.41	nM	CHEMBL178997
9.38	Ki	0.42	nM	CHEMBL538424
9.37	Ki	0.43	nM	CHEMBL5612929
9.36	Ki	0.44	nM	CHEMBL5613131
9.35	Ki	0.45	nM	CHEMBL176208
9.34	IC50	0.46	nM	CHEMBL466425
9.33	Ki	0.47	nM	CHEMBL5612188
9.33	Ki	0.47	nM	CHEMBL5613243
9.33	Ki	0.47	nM	CHEMBL5613960
9.33	Ki	0.47	nM	CHEMBL5612410
9.30	IC50	0.5	nM	CHEMBL1922270
9.30	Ki	0.5	nM	CHEMBL3618324
9.30	IC50	0.5012	nM	CHEMBL214957
9.30	IC50	0.5	nM	CHEMBL217502
9.30	Ki	0.5	nM	CHEMBL257733
9.28	IC50	0.53	nM	CHEMBL2031734
9.27	IC50	0.54	nM	CHEMBL2029372
9.27	Ki	0.54	nM	CHEMBL5612296
9.24	Kd	0.5754	nM	SNAP-7941
9.22	IC50	0.6	nM	CHEMBL2032049
9.22	Ki	0.6	nM	CHEMBL2032049
9.22	Ki	0.6	nM	CHEMBL212758
9.22	IC50	0.6	nM	CHEMBL1224229
9.20	Ki	0.63	nM	CHEMBL361392

PubChem BioAssay actives

4165 with measured affinity, of 4886 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(3S,6S,9S,12S,18S,21S,24R,29R,32S)-29-[[(2S)-1-[[(2S)-5-amino-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-5-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-6-benzyl-3,12-bis(3-carbamimidamidopropyl)-18-(2-methylpropyl)-21-(2-methylsulfanylethyl)-2,5,8,11,14,17,20,23,31-nonaoxo-9-propan-2-yl-26,27-dithia-1,4,7,10,13,16,19,22,30-nonazabicyclo[30.3.0]pentatriacontan-24-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid	426475: Displacement of [35S] 4-(1-(3,4-difluorophenyl)-2-(ethyl(3-(6-fluoro-3H-spiro[isobenzofuran-1,4’-piperidine]-1’-yl)propyl)amino)-2-oxoethyl)-3-oxopiperazine-1-sulfonic acid from human MCH1R	ki	<0.0001	uM
4-(4-fluoro-3-methylphenoxy)-3-[(3-fluorophenyl)carbamoylamino]-N-(2-pyrrolidin-1-ylethyl)benzamide	270095: Inhibition of [125I]MCH binding to human MCHR1 expressed in HEK293 cells by HT-SPA	ic50	0.0001	uM
2-(3,4-difluorophenyl)-N-(2-fluoroethyl)-N-[3-(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)propyl]-2-pyrazol-1-ylacetamide	352241: Displacement of [125I]MCH from human MCHR1 expressed in CHO cells	ic50	0.0001	uM
trans-(1S,3S)-1-N-(7-methoxy-4-methylquinolin-2-yl)-3-N-(thiophen-3-ylmethyl)cyclohexane-1,3-diamine	308202: Displacement of [125I]MCH from human MCHR1 expressed in HEK293 cells	ic50	0.0001	uM
2-(3,4-difluorophenyl)-N-ethyl-N-[3-(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)propyl]-2-pyrazol-1-ylacetamide	352241: Displacement of [125I]MCH from human MCHR1 expressed in CHO cells	ic50	0.0001	uM
(Z)-1-(3,4-difluorophenyl)-N-ethoxy-1-[4-[(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)methyl]phenyl]methanimine	446680: Displacement of [125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0001	uM
methyl (4S)-3-[3-[4-(3-acetamidophenyl)piperidin-1-yl]propylcarbamoyl]-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate;hydrochloride	688491: Binding affinity to human MCHR1 expressed in COS7 cells	kd	0.0002	uM
2-(3,4-difluorophenyl)-N-ethyl-N-[3-(5-fluorospiro[1H-2-benzofuran-3,4’-piperidine]-1’-yl)propyl]-2-(4-(35S)methylsulfonyl-2-oxopiperazin-1-yl)acetamide	426577: Binding affinity to human MCH1R expressed in CHO cells by scintillation counting per mg of protein	ki	0.0002	uM
tert-butyl 4-[1-(3,4-difluorophenyl)-2-[ethyl-[3-(5-fluorospiro[1H-2-benzofuran-3,4’-piperidine]-1’-yl)propyl]amino]-2-oxoethyl]-3-oxopiperazine-1-carboxylate	426572: Displacement of[125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0002	uM
(Z)-1-(3,4-difluorophenyl)-1-[4-[(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)methyl]phenyl]-N-methoxymethanimine	446680: Displacement of [125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0002	uM
1-[[4-[4-(3-cyanophenyl)phenyl]-1-(cyclopropylmethyl)piperidin-4-yl]methyl]-3-(3,5-dichlorophenyl)urea	1611185: Antagonist activity at MCHR1 (unknown origin) expressed in CHO cells co-expressing aequorin incubated for 10 mins by luminescence assay	ic50	0.0002	uM
1-[[4-[4-(3-cyanophenyl)phenyl]-1-propylpiperidin-4-yl]methyl]-3-(3,5-dichlorophenyl)urea	1611185: Antagonist activity at MCHR1 (unknown origin) expressed in CHO cells co-expressing aequorin incubated for 10 mins by luminescence assay	ic50	0.0003	uM
(E)-N-(4-amino-2-tert-butylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-enamide	273901: Displacement of 125I-[Phe13,Tyr19]-MCH from human MCH-R1	ic50	0.0003	uM
(NZ)-N-[(3,4-difluorophenyl)-[4-[(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)methyl]phenyl]methylidene]hydroxylamine	446680: Displacement of [125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0003	uM
(E)-N-(4-amino-2-butan-2-ylquinolin-6-yl)-3-[4-(trifluoromethyl)phenyl]prop-2-enamide	273901: Displacement of 125I-[Phe13,Tyr19]-MCH from human MCH-R1	ic50	0.0003	uM
(Z)-1-(3,4-difluorophenyl)-N-ethoxy-1-[5-[(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)methyl]-2-pyridinyl]methanimine	446680: Displacement of [125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0003	uM
1-[[4-[4-(3-cyanophenyl)phenyl]-1-propan-2-ylpiperidin-4-yl]methyl]-3-(3,5-dichlorophenyl)urea	239429: Ability to displace [125I]-MCH()0.5 nM from human MCH1R(2.5 uM) expressed in CHO cells	ki	0.0004	uM
1-[[4-[4-(3-cyanophenyl)phenyl]-1-(2-methoxyethyl)piperidin-4-yl]methyl]-3-(3,5-dichlorophenyl)urea	1611185: Antagonist activity at MCHR1 (unknown origin) expressed in CHO cells co-expressing aequorin incubated for 10 mins by luminescence assay	ic50	0.0004	uM
2-(3,4-difluorophenyl)-N-ethyl-N-[3-(5-fluorospiro[1H-2-benzofuran-3,4’-piperidine]-1’-yl)propyl]-2-(4-methylsulfonyl-2-oxopiperazin-1-yl)acetamide	446680: Displacement of [125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0004	uM
N-[3-(2-aminoquinolin-8-yl)oxypropyl]-3-chlorobenzamide	242643: Concentration required to inhibit binding of [125I]-MCH radioligand to human Melanin-concentrating hormone receptor 1 in IMR-32 I3.4.2 cell membranes	ic50	0.0004	uM
1-[4-[2-(3-cyclopropyl-3-hydroxyazetidin-1-yl)ethoxy]-3-ethylphenyl]-4-(4-cyclopropylphenoxy)-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0004	uM
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)ethoxy]phenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0004	uM
6-(4-chlorophenyl)-3-[6-(piperidin-1-ylmethyl)naphthalen-2-yl]thieno[3,2-d]pyrimidin-4-one	272586: Antagonist activity against human MCH1 receptor stably-expressed in CHO cells by Gal4/Elk1-Luc reporter assay	ic50	0.0004	uM
1-[4-[2-(3-cyclopropyl-3-hydroxyazetidin-1-yl)ethoxy]-3-methoxyphenyl]-4-(4-cyclopropylphenoxy)-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0004	uM
4-(4-chlorophenyl)-N-[8-methyl-3-(pyrrolidin-1-ylmethyl)quinolin-7-yl]benzamide	661677: Displacement of [125I]MCH from human MCHR1 expressed in CHO cells after 1 hr by scintillation counting	ic50	0.0004	uM
6-(4-chlorophenyl)-3-[6-[3-(methylamino)pyrrolidin-1-yl]-3-pyridinyl]pyrrolo[2,1-f][1,2,4]triazin-4-one	1248228: Displacement of [125I][Phe13,Tyr19]-MCH from human MCHR1 expressed in HEK293 cells by scintillation counting analysis	ki	0.0004	uM
2-(3,4-difluorophenyl)-N-[3-(6-fluorospiro[1H-furo[3,4-c]pyridine-3,4’-piperidine]-1’-yl)propyl]-N-methyl-2-pyrazol-1-ylacetamide	352241: Displacement of [125I]MCH from human MCHR1 expressed in CHO cells	ic50	0.0005	uM
(4aR,11R,11aS)-11-methyl-2-[3-(oxan-4-yl)propyl]-9-(trifluoromethyl)-1,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazole	632112: Displacement of [125I]-MCH from MCHR1 after 2 hrs by beta scintillation counting	ic50	0.0005	uM
4-(4-cyclopropylphenoxy)-1-[4-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0005	uM
4-(4-cyclopropylphenoxy)-1-[3-methoxy-4-[2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)ethoxy]phenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0005	uM
4-(4-cyclopropylphenoxy)-1-[3-methoxy-4-[2-(3-methoxyazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0005	uM
4-(4-methoxyphenyl)-N-[8-methyl-3-(pyrrolidin-1-ylmethyl)quinolin-7-yl]benzamide	661677: Displacement of [125I]MCH from human MCHR1 expressed in CHO cells after 1 hr by scintillation counting	ic50	0.0005	uM
N-[2-(2,7-diazaspiro[4.4]nonan-2-yl)quinolin-6-yl]-3-[4-(trifluoromethyl)phenyl]propanamide	273907: Displacement of 125I-[Phe13,Tyr19]-MCH from human MCH-R1	ic50	0.0005	uM
(2S)-2-[[(3R,4R)-4-[6-fluoro-2-(2-hydroxypropan-2-yl)-5-methylbenzimidazol-1-yl]-3-methoxypiperidin-1-yl]methyl]-2,3-dihydro-1H-indene-5-carbonitrile	316092: Binding affinity to MCHR1	ki	0.0005	uM
6-(4-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]pyrrolo[2,1-f][1,2,4]triazin-4-one	1248228: Displacement of [125I][Phe13,Tyr19]-MCH from human MCHR1 expressed in HEK293 cells by scintillation counting analysis	ki	0.0005	uM
1-[4-[2-(3-hydroxyazetidin-1-yl)ethoxy]-3-methoxyphenyl]-4-(4-phenylphenoxy)-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0005	uM
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0005	uM
6-(4-chlorophenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[3,2-d]pyrimidin-4-one	270769: Antagonist activity against human MCHR1 expressed in CHO cells by luciferase reporter gene assay	ic50	0.0005	uM
4-(4-fluorophenyl)-N-[8-methyl-3-(pyrrolidin-1-ylmethyl)quinolin-7-yl]benzamide	661677: Displacement of [125I]MCH from human MCHR1 expressed in CHO cells after 1 hr by scintillation counting	ic50	0.0005	uM
1-[2-[(4aR,11R,11aS)-11-methyl-9-(trifluoromethyl)-1,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl]ethyl]cyclohexane-1-carboxylic acid	661409: Displacement of [125I]-MCH from MCHR1 after 2 hrs by scintillation counting	ic50	0.0006	uM
1-[[4-[4-(3-cyanophenyl)phenyl]-1-cyclopentylpiperidin-4-yl]methyl]-3-(3,5-dichlorophenyl)urea	239429: Ability to displace [125I]-MCH()0.5 nM from human MCH1R(2.5 uM) expressed in CHO cells	ki	0.0006	uM
methyl (4S)-3-[3-[4-(3-acetamidophenyl)piperidin-1-yl]propylcarbamoyl]-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate	443384: Antagonist activity at CART form of human MCH1 receptor expressed in HEK293 cells coexpressing Galphaq assessed as inhibition of MCH-induced intracellular calcium level by FLIPR assay	kd	0.0006	uM
4-(4-cyclopropylphenoxy)-1-[4-[2-[(3R)-3-fluoropyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0006	uM
4-(4-cyclopropylphenoxy)-1-[4-[2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0006	uM
3-[6-[3-(dimethylamino)pyrrolidin-1-yl]-3-pyridinyl]-7-(4-methoxyphenyl)chromen-4-one	269770: Binding affinity to human MCH1R	ki	0.0006	uM
N-[(3S)-1-[(3R)-3-[(4,4-dimethylcyclohexyl)amino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]-5-(4-ethylphenyl)-N-methylthiophene-2-carboxamide	271223: Binding affinity to MCHR1 by competitive binding assay	ki	0.0006	uM
N-[3-[1-[4-[1-(4-fluorophenyl)benzimidazol-2-yl]butyl]piperidin-4-yl]phenyl]acetamide	504128: Displacement of [125I]MCH from human recombinant MCHR1 expressed in CHOK1 cells by scintillation proximity assay	ic50	0.0006	uM
2-(3,4-difluorophenyl)-N-ethyl-N-[3-(5-fluorospiro[1H-2-benzofuran-3,4’-piperidine]-1’-yl)propyl]-2-(2-oxopyrrolidin-1-yl)acetamide	426572: Displacement of[125I]MCH from human MCH1R expressed in CHO cells	ic50	0.0007	uM
4-(4-cyclopropylphenoxy)-1-[4-[2-(3-hydroxy-3-methylazetidin-1-yl)ethoxy]-3-methoxyphenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0007	uM
4-(4-cyclopropylphenoxy)-1-[3-ethyl-4-[2-(3-hydroxyazetidin-1-yl)ethoxy]phenyl]-2H-pyrrol-5-one	2125910: Displacement of [125I]MCH from human MCHR1 extracted from HEK293 cell membrane assessed as inhibition constant by competitive binding assay	ki	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	increases expression	2
Aflatoxin B1	increases expression	2
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, decreases methylation	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
manganese chloride	increases expression	1
vanadyl sulfate	increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
belinostat	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Haloperidol	affects binding	1
Manganese	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Pyridazines	decreases phosphorylation, affects binding, decreases activity	1

ChEMBL screening assays

267 unique, capped per target: 158 binding, 109 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL837198	Functional	Inhibition of Melanin-concentrating hormone (MCH) mediated [Ca2+] release in IMR-32 cells	Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity. — Bioorg Med Chem Lett
CHEMBL1000178	Binding	Binding affinity to MCH receptor 1	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B0GU	CHO-K1 hMCHR1	Spontaneously immortalized cell line	Female
CVCL_C0T7	ACTOne MCHR1	Transformed cell line	Female
CVCL_H372	293/MCH1	Transformed cell line	Female
CVCL_KV49	cAMP Hunter CHO-K1 MCHR1 Gi	Spontaneously immortalized cell line	Female
CVCL_LA74	PathHunter U2OS MCHR1 beta-arrestin	Cancer cell line	Female
CVCL_LA75	PathHunter U2OS MCHR1 beta-arrestin-1	Cancer cell line	Female
CVCL_LA76	PathHunter U2OS MCHR1 Total GPCR Internalization	Cancer cell line	Female
CVCL_ZI74	GeneBLAzer GPR24-Gqi5-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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