MCHR2

Summary

MCHR2 (melanin concentrating hormone receptor 2, HGNC:20867) is a protein-coding gene on chromosome 6q16.2, encoding Melanin-concentrating hormone receptor 2 (Q969V1). Receptor for melanin-concentrating hormone, coupled to G proteins that activate phosphoinositide hydrolysis.

Predicted to enable G protein-coupled peptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 84539 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 48 total
• Druggable target: yes
• MANE Select transcript: NM_001040179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20867
Approved symbol	MCHR2
Name	melanin concentrating hormone receptor 2
Location	6q16.2
Locus type	gene with protein product
Status	Approved
Aliases	SLT, MCH2, MCH2R
Ensembl gene	ENSG00000152034
Ensembl biotype	protein_coding
OMIM	606111
Entrez	84539

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000281806, ENST00000369212, ENST00000880237

RefSeq mRNA: 2 — MANE Select: NM_001040179 NM_001040179, NM_032503

CCDS: CCDS5044

Canonical transcript exons

ENST00000281806 — 6 exons

Exon	Start	End
ENSE00001003009	99942949	99943143
ENSE00001003010	99947762	99947971
ENSE00001003012	99934398	99934517
ENSE00001124842	99918519	99921255
ENSE00001124848	99955966	99956174
ENSE00001175723	99993936	99994223

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 77.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2106 / max 22.8931, expressed in 45 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74821	0.0793	39
74820	0.0569	33
74818	0.0529	31
74819	0.0215	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	77.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.70	gold quality
frontal cortex	UBERON:0001870	73.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	73.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.45	silver quality
gingival epithelium	UBERON:0001949	72.96	gold quality
neocortex	UBERON:0001950	71.40	gold quality
right frontal lobe	UBERON:0002810	71.07	gold quality
gingiva	UBERON:0001828	70.36	gold quality
superior frontal gyrus	UBERON:0002661	69.75	gold quality
anterior cingulate cortex	UBERON:0009835	68.86	gold quality
cerebral cortex	UBERON:0000956	66.54	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	66.42	gold quality
primary visual cortex	UBERON:0002436	66.21	gold quality
postcentral gyrus	UBERON:0002581	66.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	65.02	gold quality
parietal lobe	UBERON:0001872	63.84	gold quality
epithelium of nasopharynx	UBERON:0001951	63.23	gold quality
occipital lobe	UBERON:0002021	62.75	gold quality
esophagus squamous epithelium	UBERON:0006920	62.60	gold quality
nasal cavity epithelium	UBERON:0005384	60.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	59.31	gold quality
entorhinal cortex	UBERON:0002728	58.82	gold quality
middle temporal gyrus	UBERON:0002771	58.22	gold quality
temporal lobe	UBERON:0001871	57.58	gold quality
oral cavity	UBERON:0000167	57.03	gold quality
mammalian vulva	UBERON:0000997	56.95	gold quality
germinal epithelium of ovary	UBERON:0001304	56.93	gold quality
amygdala	UBERON:0001876	56.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting MCHR2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-3915	99.45	68.49	1905

Literature-anchored findings (GeneRIF, showing 10)

• 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 2. (PMID:11478907)
• MCH1 and MCH2 receptors were investigated and are different from those in SVK14 cells. (PMID:12127971)
• results of molecular simulations of MCHR2 in the free and hormone-bound forms provide suggestions on the amino acids responsible for the transfer of the structural changes from the agonist binding site to the G-protein coupling domains (PMID:15229878)
• MCHR2 is not a major contributor to polygenic obesity (PMID:17698913)
• MCHR2 positively mediates the regulation of melanin-concentrating hormone during preadipocyte differentiation and is involved in energy balance regulation without affecting preadipocyte proliferation. (PMID:19683862)
• construction of the CHO cell line and the research of MCHR2 molecular characteristics have established a good experimental basis for the further research about the function of MCHR2 gene (PMID:20099459)
• Discovery and characterization of a potent and selective antagonist of melanin-concentrating hormone receptor 2 (PMID:22123324)
• This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression. (PMID:26461262)
• evidence for the involvement of duplications in MCHR2 in alopecia areata pathogenesis in a Central European cohort (PMID:27306922)
• results are in line with some previously performed studies suggesting that MCHR2 is not a major contributor to human obesity and the Prader Willi Syndrome phenotype (PMID:29066024)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	mchr2a	ENSDARG00000007842
		ENSDARG00000101313

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), 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 2 — Q969V1 (reviewed: Q969V1)

Alternative names: G-protein coupled receptor 145, GPRv17, MCH-2R

All UniProt accessions (1): Q969V1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for melanin-concentrating hormone, coupled to G proteins that activate phosphoinositide hydrolysis.

Subcellular location. Cell membrane.

Tissue specificity. Specifically expressed in the brain, with highest levels in cerebral cortex, hippocampus and amygdala. No expression detected in the cerebellum, thalamus or hypothalamus.

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

RefSeq proteins (2): NP_001035269, NP_115892 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR008361	MCH_rcpt	Family
IPR008362	MCHR2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (42 total): helix 16, topological domain 8, transmembrane region 7, strand 4, glycosylation site 2, sequence variant 2, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8WST	ELECTRON MICROSCOPY	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969V1-F1	88.66	0.61

Antibody-complex structures (SAbDab): 1 — 8WST

Functional residue map

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

Glycosylation sites (2): 10, 17

Function

Pathways and Gene Ontology

Reactome pathways

8 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-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

MSigDB gene sets: 38 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MIR4795_3P, MIR106B_5P, MIR20A_5P, MIR126_5P, MIR513A_5P, MIR577

GO Biological Process (3): neuropeptide signaling pathway (GO:0007218), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (2): galanin receptor activity (GO:0004966), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
neuropeptide receptor activity	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCHR2	PMCH	P20382	996
MCHR2	SIM1	P81133	819
MCHR2	GNAQ	P50148	604
MCHR2	DCT	P40126	560
MCHR2	TYRP1	P17643	543
MCHR2	HCRT	O43612	536
MCHR2	MC1R	Q01726	503
MCHR2	TAS2R9	Q9NYW1	479
MCHR2	TYR	P14679	462
MCHR2	TAS2R4	Q9NYW5	435
MCHR2	MC5R	P33032	424
MCHR2	CTAG1A	P78358	424
MCHR2	CRYBG1	Q9Y4K1	421
MCHR2	EVA1C	P58658	419
MCHR2	CLNK	Q7Z7G1	414

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MCHR2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
MCHR2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
MCHR2	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	MCHR2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	MCHR2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): MCHR2 (Synthetic Lethality)

ESM2 similar proteins: C3ZQF9, E7F7V7, F1R332, O02664, O08892, O13076, O35214, O70431, O77621, P11614, P17124, P25021, P25102, P28221, P28222, P28334, P28564, P28565, P29275, P29276, P35404, P35406, P46636, P47747, P47800, P49144, P49145, P56496, P60020, P60021, P61752, P79211, P79250, P79400, P79748, Q0EAB5, Q1LZD0, Q29003, Q32ZE2, Q588Y6

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

10 interactions.

A	Effect	B	Mechanism
MCHR2	“up-regulates activity”	GNAS	binding
MCHR2	“up-regulates activity”	GNAL	binding
MCHR2	“up-regulates activity”	GNAI1	binding
MCHR2	“up-regulates activity”	GNAI3	binding
MCHR2	“up-regulates activity”	GNAQ	binding
MCHR2	“up-regulates activity”	GNA14	binding
MCHR2	“up-regulates activity”	GNA15	binding
MCHR2	“up-regulates activity”	GNA12	binding
“Melanin-concentrating hormone”	“up-regulates activity”	MCHR2	“chemical activation”
PMCH	up-regulates	MCHR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

944 predictions. Top by Δscore:

Variant	Effect	Δscore
6:99941627:T:TA	donor_gain	0.9900
6:99942941:CAACT:C	donor_loss	0.9900
6:99942942:AACTT:A	donor_loss	0.9900
6:99942943:ACTTA:A	donor_loss	0.9900
6:99942944:CTTAC:C	donor_loss	0.9900
6:99942945:TTA:T	donor_loss	0.9900
6:99942946:TACC:T	donor_loss	0.9900
6:99942947:A:AC	donor_gain	0.9900
6:99942947:A:C	donor_loss	0.9900
6:99942948:C:CC	donor_gain	0.9900
6:99943528:T:TA	donor_gain	0.9900
6:99956170:TAAAG:T	acceptor_gain	0.9900
6:99977404:CT:C	donor_gain	0.9900
6:99977404:CTCTG:C	donor_gain	0.9900
6:99934397:CCAT:C	donor_gain	0.9800
6:99943142:ACCT:A	acceptor_loss	0.9800
6:99943144:C:A	acceptor_loss	0.9800
6:99943145:T:A	acceptor_loss	0.9800
6:99955960:CCTTA:C	donor_loss	0.9800
6:99955961:CTT:C	donor_loss	0.9800
6:99955962:TTA:T	donor_loss	0.9800
6:99955963:TA:T	donor_loss	0.9800
6:99955964:A:C	donor_loss	0.9800
6:99955965:C:CG	donor_loss	0.9800
6:99956171:AAAG:A	acceptor_gain	0.9800
6:99956172:AAGCT:A	acceptor_loss	0.9800
6:99956173:AGC:A	acceptor_loss	0.9800
6:99956174:GCTG:G	acceptor_loss	0.9800
6:99956175:C:CC	acceptor_gain	0.9800
6:99956176:T:A	acceptor_loss	0.9800

AlphaMissense

2240 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:99947857:C:A	W99C	0.997
6:99947857:C:G	W99C	0.997
6:99947859:A:G	W99R	0.995
6:99947859:A:T	W99R	0.995
6:99947770:A:C	S128R	0.989
6:99947770:A:T	S128R	0.989
6:99947772:T:G	S128R	0.989
6:99942985:C:G	C184S	0.985
6:99942986:A:T	C184S	0.985
6:99947837:C:G	C106S	0.985
6:99947838:A:T	C106S	0.985
6:99947932:G:C	N74K	0.985
6:99947932:G:T	N74K	0.985
6:99921066:G:C	S299R	0.984
6:99921066:G:T	S299R	0.984
6:99921068:T:G	S299R	0.984
6:99921183:A:C	F260L	0.984
6:99921183:A:T	F260L	0.984
6:99921185:A:G	F260L	0.984
6:99947858:C:G	W99S	0.982
6:99921063:G:C	S300R	0.980
6:99921063:G:T	S300R	0.980
6:99921065:T:G	S300R	0.980
6:99943064:A:G	W158R	0.979
6:99943064:A:T	W158R	0.979
6:99955996:C:T	G51D	0.979
6:99956015:A:G	C45R	0.979
6:99942985:C:T	C184Y	0.975
6:99947836:G:C	C106W	0.975
6:99947837:C:T	C106Y	0.975

dbSNP variants (sampled 300 via entrez): RS1000001105 (6:99994723 A>C), RS1000080935 (6:99957024 T>G), RS1000116874 (6:99995153 ATC>A), RS1000121061 (6:99920136 T>G), RS1000131398 (6:99985734 C>G), RS1000165779 (6:99972661 C>G), RS1000212901 (6:99972757 T>C), RS1000253464 (6:99988373 C>T), RS1000277227 (6:99920535 C>G,T), RS1000282309 (6:99976779 G>A), RS1000290398 (6:99937886 G>A,C,T), RS1000319828 (6:99965377 C>T), RS1000325401 (6:99980144 T>C), RS1000365063 (6:99975160 C>T), RS1000462401 (6:99943997 G>A)

Disease associations

OMIM: gene MIM:606111 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000880_9	Menarche (age at onset)	2.000000e-08
GCST002541_25	Menarche (age at onset)	3.000000e-16
GCST002541_51	Menarche (age at onset)	9.000000e-14
GCST002541_52	Menarche (age at onset)	8.000000e-12
GCST006041_19	Major depressive disorder	6.000000e-08
GCST006491_9	Circulating fibroblast growth factor 23 levels	8.000000e-07
GCST006956_19	Erectile dysfunction	6.000000e-14
GCST007118_1	Erectile dysfunction	2.000000e-37
GCST010002_330	Refractive error	2.000000e-15
GCST010243_50	Apolipoprotein B levels	3.000000e-15
GCST010244_101	Triglyceride levels	5.000000e-09
GCST010245_110	LDL cholesterol levels	6.000000e-13
GCST010988_372	Adult body size	4.000000e-09
GCST011494_33	Daytime nap	3.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111437 (PROTEIN FAMILY), CHEMBL4106188 (SELECTIVITY GROUP), CHEMBL5038 (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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
[Phe13,Tyr19]MCH	Full agonist	9.2	pIC50
melanin-concentrating hormone	Full agonist	9.2	pIC50
compound 38 [PMID: 22123324]	Antagonist	9.0	pIC50
Ac-hMCH-(6-16)-NH2	Full agonist	8.8	pIC50
[Ava9,10,Ava14,15]-Ac-hMCH6-16-NH2	Antagonist	7.3	pIC50
MCH (salmon)	Full agonist	7.1	pIC50
ATC0065	Antagonist	5.9	pIC50

Binding affinities (BindingDB)

34 measured of 34 human assays (34 total across all organisms); most potent 34 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
hAc-MCH(6-16)-NH2	KI	0.16 nM
Salmon MCH	KI	0.2 nM
[Phe13,Tyr19]MCH	KI	0.3 nM
N-Me-Nle8	KI	0.34 nM
N-Me-Arg11	KI	0.55 nM
hMCH	KI	1.5 nM
Ava14,15	KI	1.8 nM
N-Me-Gly10	KI	3.3 nM
Ava9,10	KI	4 nM
Gva6,Nle8,Ava14,15	KI	4.7 nM
Gva6,Ava9,10	KI	5 nM
D-Arg6,Ava9,10	KI	6.8 nM
Gbu6,Ava14,15	KI	7.9 nM
Gva6,cisAcx14,15	KI	10 nM
D-Arg6,Ava14,15	KI	11.3 nM
Gva6,betaAla14,15	KI	14 nM
Gva6,gammaAbu14,15	KI	24 nM
Gva6,Ala12,Ava14,15	KI	25 nM
Ala8,Ava14,15	KI	38 nM
Gpr6,Ava14,15	KI	43 nM
Gva6,Ava9,10,Ava14,15	KI	45 nM
N-Me-Leu9	KI	62 nM
Ava9,10,Ava14,15	KI	65 nM
Gva6,Ava14,15, OH	KI	66 nM
Gva6,Gly14,15	KI	67 nM
D-Arg6,Ava9,10,Ava14,15	KI	69 nM
Gva6,Ala8,Ava14,15	KI	83 nM
Gva6,D-Cys7,Ava14,15	KI	120 nM
des(Ac-Arg6),Ava14,15	KI	190 nM
Gva6,alphaAbu8,Ava14,15	KI	320 nM
N-Me-Arg14	KI	330 nM
D-Cys7,Ava14,15	KI	340 nM
Gva6,desLeu9,Ava14,15	KI	1350 nM
Aoct8,9,10	KI	4800 nM

ChEMBL bioactivities

83 potent at pChembl≥5 of 86 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL1934121
10.00	IC50	0.1	nM	CHEMBL1934123
9.00	IC50	1	nM	CHEMBL1934127
9.00	IC50	1	nM	CHEMBL1934130
8.80	Ki	1.6	nM	CHEMBL557629
8.43	IC50	3.7	nM	CHEMBL196667
8.40	IC50	4	nM	CHEMBL1934109
8.40	IC50	4	nM	CHEMBL1934112
8.35	IC50	4.5	nM	CHEMBL194408
8.33	IC50	4.7	nM	CHEMBL197026
8.20	IC50	6.3	nM	CHEMBL195635
8.19	IC50	6.4	nM	CHEMBL197050
8.17	IC50	6.8	nM	CHEMBL427540
8.17	IC50	6.8	nM	CHEMBL373084
8.15	IC50	7.1	nM	CHEMBL196581
8.10	IC50	8	nM	CHEMBL1934125
8.08	IC50	8.4	nM	CHEMBL196196
8.06	IC50	8.7	nM	CHEMBL194837
8.00	IC50	10	nM	CHEMBL1934116
8.00	IC50	10	nM	CHEMBL1934126
8.00	IC50	10	nM	CHEMBL1934128
7.96	IC50	11	nM	CHEMBL179501
7.89	IC50	13	nM	CHEMBL1934122
7.89	Ki	13	nM	CHEMBL1934130
7.82	IC50	15	nM	CHEMBL214585
7.60	IC50	25	nM	CHEMBL214731
7.58	IC50	26	nM	CHEMBL215661
7.54	IC50	29	nM	CHEMBL214021
7.52	IC50	30	nM	CHEMBL1934114
7.46	IC50	35	nM	CHEMBL216554
7.44	IC50	36	nM	CHEMBL214585
7.36	IC50	44	nM	CHEMBL266725
7.34	IC50	46	nM	CHEMBL386281
7.25	IC50	56	nM	CHEMBL215661
7.24	IC50	57	nM	CHEMBL216104
7.18	IC50	66	nM	CHEMBL274168
7.16	IC50	70	nM	CHEMBL1934108
7.10	IC50	80	nM	CHEMBL1934117
7.02	IC50	95	nM	CHEMBL384919
7.00	IC50	100	nM	CHEMBL1934107
7.00	IC50	100	nM	CHEMBL1934113
7.00	IC50	100	nM	CHEMBL1934119
6.98	IC50	104	nM	CHEMBL426292
6.97	IC50	106	nM	CHEMBL216524
6.96	IC50	110	nM	CHEMBL216180
6.83	IC50	147	nM	CHEMBL196599
6.82	IC50	150	nM	CHEMBL1934118
6.79	IC50	162	nM	CHEMBL216482
6.77	IC50	171	nM	CHEMBL197054
6.76	IC50	173	nM	CHEMBL384111

PubChem BioAssay actives

83 with measured affinity, of 361 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
N-[(1R)-1’-(9H-carbazol-3-ylmethyl)spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0001	uM
N-[1’-[(9-ethylcarbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0001	uM
3-[[(1R)-1-acetamidospiro[1,2-dihydroindene-3,4’-piperidine]-1’-yl]methyl]carbazole-9-carboxamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0010	uM
N-[(1R)-1’-[(6-chloro-9H-carbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0010	uM
(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	426575: 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 MCH2R	ki	0.0016	uM
2-(2,4-dichlorophenoxy)-N-(4-methyl-2-piperazin-1-ylquinolin-6-yl)acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0037	uM
3-(spiro[indene-1,4’-piperidine]-1’-ylmethyl)carbazole-9-carboxamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0040	uM
N,N-dimethyl-3-(spiro[indene-1,4’-piperidine]-1’-ylmethyl)carbazole-9-carboxamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0040	uM
2-(2,4-dichlorophenoxy)-N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methylquinolin-6-yl]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0045	uM
N-[2-(4-aminopiperidin-1-yl)-4-methylquinolin-6-yl]-2-[4-(trifluoromethoxy)phenoxy]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0047	uM
N-[4-methyl-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinolin-6-yl]-2-[4-(trifluoromethoxy)phenoxy]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0063	uM
(E)-N-[2-[2-hydroxyethyl(methyl)amino]-4-methylquinolin-6-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-enamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0064	uM
N-[2-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-4-methylquinolin-6-yl]-2-[4-(trifluoromethoxy)phenoxy]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0068	uM
2-(2,4-dichlorophenoxy)-N-[4-methyl-2-[methyl-[2-(methylamino)ethyl]amino]quinolin-6-yl]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0068	uM
N-[2-[3-(dimethylamino)propylamino]-4-methylquinolin-6-yl]-2-[4-(trifluoromethoxy)phenoxy]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0071	uM
N-[(1S,2S)-1’-(9H-carbazol-3-ylmethyl)-2-hydroxyspiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0080	uM
(E)-N-[2-[2-(dimethylamino)ethylamino]-4-methylquinolin-6-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-enamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0084	uM
2-(2,4-dichlorophenoxy)-N-[2-[2-(dimethylamino)ethoxy]-4-methylquinolin-6-yl]acetamide	255147: Displacement of 15 pM [125I]-MCH from human MCH2R expressed in CHO-K1 in whole-cell binding assay	ic50	0.0087	uM
(2R)-1’-(9H-carbazol-3-ylmethyl)spiro[1,2-dihydroindene-3,4’-piperidine]-2-ol	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0100	uM
N-[(1R)-1’-[(6-fluoro-9H-carbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0100	uM
N-[(1R)-1’-[(6-bromo-9H-carbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0100	uM
2-(4-phenylmethoxyphenyl)-N-[1-(2-pyrrolidin-1-ylethyl)indazol-6-yl]acetamide	248088: Inhibition of Melanin-concentrating hormone (MCH) mediated [Ca2+] release in IMR-32 cells	ic50	0.0110	uM
N-[(1S)-1’-(9H-carbazol-3-ylmethyl)spiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0130	uM
N-[1-(6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-7-yl)piperidin-4-yl]-6-fluoro-4-oxochromene-2-carboxamide	273884: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0150	uM
N-[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]-6-fluoro-4-oxochromene-2-carboxamide	273884: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0250	uM
N-[1-(6-acetamido-2,3-dihydro-1H-inden-1-yl)piperidin-4-yl]-7-fluoro-4-oxochromene-2-carboxamide	273884: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0260	uM
N-[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]-7-fluoro-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0290	uM
1’-[(9-ethylcarbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-2-ol	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0300	uM
N-[1-(1-benzofuran-5-ylmethyl)piperidin-4-yl]-7-fluoro-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0350	uM
7-fluoro-N-[1-[(1-methyl-2-oxoquinolin-7-yl)methyl]piperidin-4-yl]-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0440	uM
7-fluoro-4-oxo-N-[1-[(2-oxochromen-7-yl)methyl]piperidin-4-yl]chromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0460	uM
N-[1-(1-benzothiophen-5-ylmethyl)piperidin-4-yl]-7-fluoro-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0570	uM
7-fluoro-N-[1-(1H-indol-6-ylmethyl)piperidin-4-yl]-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0660	uM
1-[3-(spiro[indene-1,4’-piperidine]-1’-ylmethyl)carbazol-9-yl]ethanone	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0700	uM
(2S)-1’-(9H-carbazol-3-ylmethyl)spiro[1,2-dihydroindene-3,4’-piperidine]-2-ol	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.0800	uM
7-fluoro-4-oxo-N-[1-(3-oxo-4,6,7,8-tetrahydrocyclopenta[g][1,4]benzoxazin-6-yl)piperidin-4-yl]chromene-2-carboxamide	273884: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.0950	uM
1-[3-(spiro[indene-1,4’-piperidine]-1’-ylmethyl)carbazol-9-yl]propan-1-one	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.1000	uM
1’-(9H-carbazol-3-ylmethyl)spiro[indene-1,4’-piperidine]	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.1000	uM
N-[(1S,2S)-1’-[(9-ethylcarbazol-3-yl)methyl]-2-hydroxyspiro[1,2-dihydroindene-3,4’-piperidine]-1-yl]acetamide	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.1000	uM
1-(4-phenoxyphenyl)-3-[1-(2-pyrrolidin-1-ylethyl)indazol-5-yl]urea	248088: Inhibition of Melanin-concentrating hormone (MCH) mediated [Ca2+] release in IMR-32 cells	ic50	0.1040	uM
N-[1-(1,3-benzoxazol-6-ylmethyl)piperidin-4-yl]-7-fluoro-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.1060	uM
7-fluoro-N-[1-(1H-indol-5-ylmethyl)piperidin-4-yl]-4-oxochromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.1100	uM
1-[1-[2-(cyclopentylamino)ethyl]indazol-5-yl]-3-(4-phenoxyphenyl)urea	248088: Inhibition of Melanin-concentrating hormone (MCH) mediated [Ca2+] release in IMR-32 cells	ic50	0.1470	uM
(1S,2S)-1’-[(9-ethylcarbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-1,2-diol	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.1500	uM
7-fluoro-4-oxo-N-[1-[(2-oxo-1H-quinolin-7-yl)methyl]piperidin-4-yl]chromene-2-carboxamide	273946: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.1620	uM
1-[2-[5-[(4-phenoxyphenyl)carbamoylamino]indazol-1-yl]ethyl]piperidine-4-carboxamide	248088: Inhibition of Melanin-concentrating hormone (MCH) mediated [Ca2+] release in IMR-32 cells	ic50	0.1710	uM
7-fluoro-4-oxo-N-[1-(2-oxo-3,5,6,7-tetrahydrocyclopenta[f][1,3]benzoxazol-5-yl)piperidin-4-yl]chromene-2-carboxamide	273884: Inhibition of MCH-mediated calcium release in IMR-32 cells	ic50	0.1730	uM
1-[2-(4-phenoxyphenyl)ethyl]-3-[1-(2-pyrrolidin-1-ylethyl)indazol-6-yl]urea	248088: Inhibition of Melanin-concentrating hormone (MCH) mediated [Ca2+] release in IMR-32 cells	ic50	0.1780	uM
1’-[(9-methylsulfonylcarbazol-3-yl)methyl]spiro[indene-1,4’-piperidine]	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.2000	uM
1’-[(9-ethylcarbazol-3-yl)methyl]spiro[1,2-dihydroindene-3,4’-piperidine]-1-ol	638484: Antagonist activity at human MCHR2 receptor expressed in CHO cells assessed as inhibition of MCH-stimulated Ca2+ flux preincubated for 10 mins prior to MCH-stimulation by FLIPR assay	ic50	0.2000	uM

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Aflatoxin B1	decreases methylation	2
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
Acetaminophen	increases expression	1
Valproic Acid	decreases methylation	1

ChEMBL screening assays

35 unique, capped per target: 21 binding, 14 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
CHEMBL1039135	Binding	Inhibition of human MCH2R	Discovery of novel diarylketoxime derivatives as selective and orally active melanin-concentrating hormone 1 receptor antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 spontaneously immortalized cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H463	CHO-K1/MCH2	Spontaneously immortalized cell line	Female
CVCL_L602	MCHR2-SHG-44	Cancer cell line	Female
CVCL_LA77	PathHunter U2OS MCHR2 beta-arrestin	Cancer cell line	Female
CVCL_U366	CHO-MCHR2	Spontaneously immortalized cell line	Female
CVCL_ZK87	GeneBLAzer MCHR2-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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