NPY5R

Summary

NPY5R (neuropeptide Y receptor Y5, HGNC:7958) is a protein-coding gene on chromosome 4q32.2, encoding Neuropeptide Y receptor type 5 (Q15761). Receptor for neuropeptide Y and peptide YY.

The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 4889 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006174

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7958
Approved symbol	NPY5R
Name	neuropeptide Y receptor Y5
Location	4q32.2
Locus type	gene with protein product
Status	Approved
Aliases	NPYR5
Ensembl gene	ENSG00000164129
Ensembl biotype	protein_coding
OMIM	602001
Entrez	4889

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000338566, ENST00000506953, ENST00000515560, ENST00000901845, ENST00000919917, ENST00000919918, ENST00000919919, ENST00000919920, ENST00000919921, ENST00000919922, ENST00000919923, ENST00000919924, ENST00000919925, ENST00000919926, ENST00000967945, ENST00000967946, ENST00000967947, ENST00000967948

RefSeq mRNA: 3 — MANE Select: NM_006174 NM_001317091, NM_001317092, NM_006174

CCDS: CCDS3804

Canonical transcript exons

ENST00000338566 — 4 exons

Exon	Start	End
ENSE00001081707	163347452	163347522
ENSE00001293127	163345714	163345753
ENSE00001349268	163343892	163344000
ENSE00001365185	163350265	163351934

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 92.03.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6734 / max 83.3436, expressed in 259 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50399	0.6310	249
203406	0.0424	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.03	gold quality
blood vessel layer	UBERON:0004797	74.47	gold quality
adipose tissue	UBERON:0001013	73.36	gold quality
tibial artery	UBERON:0007610	73.01	gold quality
popliteal artery	UBERON:0002250	73.00	gold quality
cortical plate	UBERON:0005343	72.84	gold quality
spleen	UBERON:0002106	72.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.92	gold quality
connective tissue	UBERON:0002384	71.87	gold quality
descending thoracic aorta	UBERON:0002345	71.79	gold quality
metanephros cortex	UBERON:0010533	71.33	gold quality
aorta	UBERON:0000947	71.20	gold quality
prefrontal cortex	UBERON:0000451	71.04	gold quality
right adrenal gland cortex	UBERON:0035827	70.70	gold quality
left adrenal gland cortex	UBERON:0035825	70.62	gold quality
left adrenal gland	UBERON:0001234	70.46	gold quality
right adrenal gland	UBERON:0001233	70.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	69.16	gold quality
thoracic aorta	UBERON:0001515	69.15	gold quality
adrenal cortex	UBERON:0001235	68.87	gold quality
nucleus accumbens	UBERON:0001882	68.85	gold quality
ascending aorta	UBERON:0001496	68.73	gold quality
omental fat pad	UBERON:0010414	68.52	gold quality
peritoneum	UBERON:0002358	68.45	gold quality
adrenal gland	UBERON:0002369	67.92	gold quality
right coronary artery	UBERON:0001625	67.14	gold quality
caudate nucleus	UBERON:0001873	67.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.82	gold quality
Brodmann (1909) area 10	UBERON:0013541	66.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting NPY5R, 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-656-3P	100.00	72.15	2788
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-203B-3P	97.82	66.27	979

Literature-anchored findings (GeneRIF, showing 15)

• The authenticity of this transcript was confirmed by isolating part of its 5’UTR and analysing its tissue distribution,, we have shown that the two AUG triplets contained in the 5’ untranslated region of Y5(L) mRNA did not affect receptor expression (PMID:12398768)
• Functional studies of new ligands for this receptor. (PMID:15601626)
• Neuropeptide-Y induced endothelial cell migration was mimicked by agonists and fully blocked by antagonists for any specific NPY receptor (NPY5R). (PMID:16891622)
• single nucleotide polymorphisms in the NPY5R gene may have a role in dyslipidemia (elevated triglyceride concentrations and reduced high-density lipoprotein levels) in Mexican Americans (PMID:17426313)
• Sequence variations in neuropeptide Y receptor genes (NPY5R and NPY2R) are associated with alcohol dependence, cocaine dependence, and comorbid alcohol and cocaine dependence. (PMID:18828811)
• Results suggest that rabbit and human Y1, Y2 and Y5 receptor subtypes are well conserved, whereas Y4 receptors are less well conserved. (PMID:19481128)
• NPY1R and NPY5R have roles in nutrient-specific food intake in Europeans (PMID:19759915)
• Together, our results suggest that Y5R plays an important role in cancer cell growth and migration and could be a novel therapeutic target for breast cancer. (PMID:20332211)
• Variations in genes AGRP, CPE, GHRL, GLP1R, HTR2A, NPY1R, NPY5R, SOCS3 and STAT3 showed modest associations with BMI in European Americans. (PMID:23900445)
• these data highlight a novel mechanism by which NPY may promote breast cancer progression, and further implicate a pathological role of the NPY Y5R. (PMID:23932937)
• NPY5R is an inducible pro-survival factor that is responsible for chemoresistance in neuroblastoma cells. (PMID:25132261)
• Y1R and Y5R might be the dominant receptors that mediate the effect of NPY-induced fat accumulation in both subcutaneous and visceral adipose tissues. Y1R and Y5R in visceral adipose tissue might be targets of drug development in prevention or treatment of obesity. (PMID:29763369)
• Molecular crosstalk between Y5 receptor and neuropeptide Y drives liver cancer. (PMID:31999643)
• Expression of hypoxia inducible factor-dependent neuropeptide Y receptors Y1 and Y5 sensitizes hypoxic cells to NPY stimulation. (PMID:35093384)
• Neuropeptide Y promotes hepatic apolipoprotein A1 synthesis and secretion through neuropeptide Y Y5 receptor. (PMID:35660638)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npy4r	ENSDARG00000043341
mus_musculus	Npy5r	ENSMUSG00000044014
rattus_norvegicus	Npy5r	ENSRNOG00000014172

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), 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

Neuropeptide Y receptor type 5 — Q15761 (reviewed: Q15761)

Alternative names: NPY-Y5 receptor

All UniProt accessions (1): Q15761

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.

Subcellular location. Cell membrane.

Tissue specificity. Brain; hypothalamus.

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

RefSeq proteins (3): NP_001304020, NP_001304021, NP_006165* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000393	NPY5_rcpt	Family
IPR000611	NPY_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (20 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15761-F1	75.70	0.37

Functional residue map

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

Post-translational modifications (1): 442

Disulfide bonds (1): 114–198

Glycosylation sites (2): 10, 17

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 177 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_RESPONSE_TO_ETHANOL, GOBP_GLUTAMATE_SECRETION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, BENPORATH_ES_WITH_H3K27ME3, chr4q32, GOBP_BEHAVIOR, GOBP_CARDIAC_LEFT_VENTRICLE_MORPHOGENESIS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, STAEGE_EWING_FAMILY_TUMOR, GOBP_INFLAMMATORY_RESPONSE, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_MUSCLE_CELL_PROLIFERATION

GO Biological Process (19): positive regulation of acute inflammatory response (GO:0002675), negative regulation of acute inflammatory response to antigenic stimulus (GO:0002865), outflow tract morphogenesis (GO:0003151), cardiac left ventricle morphogenesis (GO:0003214), G protein-coupled receptor signaling pathway (GO:0007186), chemical synaptic transmission (GO:0007268), negative regulation of glutamate secretion (GO:0014050), negative regulation of synaptic transmission, GABAergic (GO:0032229), eating behavior (GO:0042755), negative regulation of apoptotic process (GO:0043066), positive regulation of smooth muscle cell proliferation (GO:0048661), generation of ovulation cycle rhythm (GO:0060112), positive regulation of ERK1 and ERK2 cascade (GO:0070374), synaptic signaling via neuropeptide (GO:0099538), cell communication (GO:0007154), signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218), positive regulation of cell population proliferation (GO:0008284), signaling (GO:0023052)

GO Molecular Function (5): peptide YY receptor activity (GO:0001601), pancreatic polypeptide receptor activity (GO:0001602), neuropeptide Y receptor activity (GO:0004983), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (5): plasma membrane (GO:0005886), neuron projection (GO:0043005), presynapse (GO:0098793), GABA-ergic synapse (GO:0098982), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
G protein-coupled receptor signaling pathway	2
neuropeptide Y receptor activity	2
synapse	2
cellular anatomical structure	2
acute inflammatory response	1
regulation of acute inflammatory response	1
positive regulation of inflammatory response	1
acute inflammatory response to antigenic stimulus	1
negative regulation of acute inflammatory response	1
negative regulation of inflammatory response to antigenic stimulus	1
regulation of acute inflammatory response to antigenic stimulus	1
heart morphogenesis	1
anatomical structure morphogenesis	1
cardiac ventricle morphogenesis	1
G protein-coupled receptor activity	1
signal transduction	1
anterograde trans-synaptic signaling	1
glutamate secretion	1
regulation of glutamate secretion	1
negative regulation of organic acid transport	1
negative regulation of amino acid transport	1
negative regulation of secretion by cell	1
regulation of synaptic transmission, GABAergic	1
negative regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
feeding behavior	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
positive regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
ovulation cycle process	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
synaptic signaling	1
cell communication	1
signaling	1

Protein interactions and networks

STRING

777 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPY5R	NPY	P01303	996
NPY5R	PYY	P10082	972
NPY5R	PPY	P01298	737
NPY5R	AGRP	O00253	717
NPY5R	NPR1	P16066	682
NPY5R	POMC	P01189	678
NPY5R	MC4R	P32245	676
NPY5R	RLN3	Q8WXF3	606
NPY5R	GLRB	P48167	582
NPY5R	NPY1R	P25929	549
NPY5R	SSTR1	P30872	503
NPY5R	MCHR1	Q99705	484
NPY5R	RXFP1	Q9HBX9	478
NPY5R	MC3R	P41968	470
NPY5R	HTR3B	O95264	468
NPY5R	HCRT	O43612	468

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NUPR1	NPY5R	psi-mi:“MI:0915”(physical association)	0.370
NPY5R	RNF181	psi-mi:“MI:0915”(physical association)	0.370
EP300	NPY5R	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (9): NPY5R (Proximity Label-MS), NPY5R (Proximity Label-MS), NPY5R (Proximity Label-MS), NPY5R (Proximity Label-MS), NPY5R (Proximity Label-MS), NPY5R (Proximity Label-MS), NPY5R (Proximity Label-MS), RNF181 (Two-hybrid), NUPR1 (Two-hybrid)

ESM2 similar proteins: B2RPY5, B3DM66, O02213, O02824, O62729, O70342, O73810, O77680, P14416, P18130, P18901, P20288, P21728, P21918, P24628, P34973, P35348, P41595, P41596, P42288, P42289, P42290, P42291, P50130, P52702, P53452, P53453, P60026, P61168, P61169, P97718, Q02152, Q09502, Q15761, Q16950, Q18534, Q18775, Q19084, Q2KNE5, Q2YDN1

Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, F1MV99, G4WMX4, O02835, O02836, O08725, O42179, O43614, O54799, O62729, O62809, O70342, O77408, P0DQD5, P11617, P20288, P22270, P24053, P24628, P25929, P25931, P28336, P29274, P30731, P30938, P30975, P32251, P35346, P35371, P41143, P47211, P47751, P49146, P49219, P49285, P49288, P49683, P50391

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NPY	up-regulates	NPY5R	binding
PYY	up-regulates	NPY5R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1027 predictions. Top by Δscore:

Variant	Effect	Δscore
4:163347519:GAAA:G	donor_gain	1.0000
4:163347523:G:GG	donor_gain	1.0000
4:163345752:GG:G	donor_gain	0.9900
4:163345753:GG:G	donor_gain	0.9900
4:163347520:A:T	donor_gain	0.9900
4:163347559:T:G	donor_gain	0.9900
4:163347568:GCCT:G	donor_gain	0.9900
4:163350259:A:AG	acceptor_gain	0.9900
4:163350260:A:G	acceptor_gain	0.9900
4:163350262:CAGG:C	acceptor_loss	0.9900
4:163350263:A:AT	acceptor_loss	0.9900
4:163350264:GGACT:G	acceptor_gain	0.9900
4:163344134:G:GT	donor_gain	0.9800
4:163347234:TAGAG:T	acceptor_gain	0.9800
4:163347235:AGAGA:A	acceptor_gain	0.9800
4:163347236:GAGAG:G	acceptor_gain	0.9800
4:163347518:AGAAA:A	donor_gain	0.9800
4:163347519:GAAAG:G	donor_gain	0.9800
4:163350263:AG:A	acceptor_gain	0.9800
4:163350264:GG:G	acceptor_gain	0.9800
4:163344000:GGT:G	donor_loss	0.9700
4:163344001:GTACG:G	donor_loss	0.9700
4:163344002:T:G	donor_loss	0.9700
4:163350261:GCA:G	acceptor_gain	0.9700
4:163350263:A:AG	acceptor_gain	0.9700
4:163350264:G:GG	acceptor_gain	0.9700
4:163350264:GGA:G	acceptor_gain	0.9700
4:163347309:A:G	acceptor_gain	0.9600
4:163347520:AAAGT:A	donor_loss	0.9600
4:163347521:AA:A	donor_gain	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000175280 (4:163345554 T>C,G), RS1000438912 (4:163345196 A>C), RS1000730749 (4:163352597 C>T), RS1000910087 (4:163351865 C>T), RS1001010596 (4:163344647 C>A,T), RS1001289694 (4:163350414 C>G), RS1001376224 (4:163349997 G>A,C), RS1001439226 (4:163343882 C>G), RS1001441794 (4:163344904 C>G,T), RS1001601133 (4:163348471 A>G,T), RS1001902127 (4:163349737 C>T), RS1001934581 (4:163350052 C>T), RS1002185620 (4:163342603 C>T), RS1002291986 (4:163348868 A>T), RS1002576172 (4:163346761 T>C,G)

Disease associations

OMIM: gene MIM:602001 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4561 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 368 (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
CHEMBL595573	MK-0557	3	31
CHEMBL2016681	VELNEPERIT	2	326
CHEMBL4540843	PANCREATIC POLYPEPTIDE	2	1
CHEMBL438945	HUMAN NEUROPEPTIDE Y	1	10

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4234955	NPY1R, NPY5R		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Neuropeptide Y receptors

Most potent curated ligand interactions (23 total), top 23:

Ligand	Action	Affinity	Parameter
CGP 71683A	Antagonist	9.5	pKi
[125I][cPP(1-7), NPY(19-23), Ala31, Aib32, Gln34]hPP	Agonist	9.3	pKd
neuropeptide Y	Full agonist	9.1	pKi
[Leu31,Pro34]NPY (pig)	Full agonist	9.1	pKi
peptide YY	Full agonist	8.9	pKi
NPY-(2-36)	Full agonist	8.9	pKi
[125I][PP1-17,Ala31,Aib32]NPY (human)	Full agonist	8.9	pKd
[Leu31,Pro34]PYY (human)	Full agonist	8.8	pKi
[PP1-17,Ala31,Aib32]NPY (human)	Full agonist	8.8	pKi
[Ala31,Aib32]NPY	Full agonist	8.4	pKi
FMS586	Antagonist	8.4	pIC50
JCF 109	Antagonist	8.3	pKi
[Ala31,Aib32]NPY (pig)	Full agonist	8.2	pIC50
[D-Trp32]NPY	Full agonist	8.1	pKi
NPY-(3-36) (pig)	Full agonist	8.0	pKi
pancreatic polypeptide	Full agonist	8.0	pKi
PYY-(3-36)	Full agonist	8.0	pKi
L-152,804	Antagonist	7.6	pKi
NPY-(13-36) (pig)	Full agonist	7.3	pKi
PYY-(13-36) (mouse, rat, pig)	Full agonist	7.1	pKi
pancreatic polypeptide	Full agonist	6.4	pKi
GR231118	Full agonist	6.4	pKi
NPY-(18-36) (human, pig)	Full agonist	6.2	pKi

Binding affinities (BindingDB)

21 measured of 23 human assays (31 total across all organisms); most potent 21 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Des-AA11-18[Cys7,21,D-Lys9 (Ac), Pro34]-NPY	KI	0.2 nM
Des-AA11-18[Cys7,21,D-Lys9 (Ac)]-NPY	KI	0.7 nM
N-[[4-[[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]amino]cyclohexyl]methyl]ethanesulfonamide	IC50	0.81 nM	US-8916594: 5-membered ring heteroaromatic derivatives having NPY Y5 receptor antagonistic activity
N-[[4-[[3-(3,4-difluorophenyl)-1,2,4-oxadiazol-5-yl]amino]cyclohexyl]methyl]ethanesulfonamide	IC50	0.86 nM	US-8916594: 5-membered ring heteroaromatic derivatives having NPY Y5 receptor antagonistic activity
[D-Arg25]-NPY	KI	0.9 nM
Des-AA11-18[Cys7,21,D-Lys9 (Ac), D-His26, Pro34]-NPY	KI	1.2 nM
PYY	KI	2 nM
[D-His26]-NPY	KI	2 nM
Des-AA11-18[Cys7,21,D-Lys9 (Ac), D-His26]-NPY	KI	2.2 nM
NPY2-36, rat, human	KI	2.45 nM
[D-Arg25, D-His26]-NPY	KI	9.7 nM
PYY 3-36, rat	KI	33.1 nM
Des-AA10-17[Cys7,21, Pro34]-NPY	KI	37 nM
CAS_59763-91-6	KI	170 nM
NSC_41735	KI	468 nM
PP [cPP(1-7), NPY(19-23), Ala31, Aib32, Gln34], human	KI	530 nM
NPY [Ala31, Aib32], porcine	KI	700 nM
PYY 3-36	KI	760 nM
NPY22-36, rat, human	KI	1000 nM
NPY [hPP(1-17), Ala31,Aib32], human	KI	1000 nM
NPY 18-36	KI	1200 nM

ChEMBL bioactivities

1375 potent at pChembl≥5 of 1382 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	Ki	0.02512	nM	CHEMBL1257993
10.50	Ki	0.03162	nM	CHEMBL1258111
10.40	Ki	0.03981	nM	CHEMBL1258225
10.20	Ki	0.0631	nM	CHEMBL1257992
10.20	Ki	0.0631	nM	CHEMBL1258341
10.20	Ki	0.0631	nM	CHEMBL1258787
10.10	Ki	0.07943	nM	CHEMBL1258110
10.00	Ki	0.1	nM	CHEMBL1257636
10.00	Ki	0.1	nM	CHEMBL1258340
10.00	Ki	0.1	nM	CHEMBL1258453
10.00	Ki	0.1	nM	CHEMBL1258674
9.90	Ki	0.1259	nM	CHEMBL1257637
9.80	Ki	0.1585	nM	CHEMBL1257761
9.80	Ki	0.1585	nM	CHEMBL1257760
9.80	Ki	0.1585	nM	CHEMBL1258673
9.80	Ki	0.1585	nM	CHEMBL1289154
9.70	IC50	0.2	nM	CHEMBL492370
9.70	Ki	0.1995	nM	CHEMBL1258454
9.70	Ki	0.1995	nM	CHEMBL1258562
9.70	Ki	0.1995	nM	CHEMBL1289153
9.70	IC50	0.2	nM	CHEMBL342438
9.64	IC50	0.23	nM	FR-236478
9.60	Ki	0.2512	nM	CHEMBL1258788
9.52	Ki	0.3	nM	CHEMBL2013020
9.52	Ki	0.3	nM	CHEMBL1829320
9.52	Ki	0.3	nM	CHEMBL61880
9.52	IC50	0.3	nM	CHEMBL138379
9.52	IC50	0.3	nM	CHEMBL135143
9.52	IC50	0.3	nM	CHEMBL343817
9.50	Ki	0.3162	nM	CHEMBL1258224
9.50	Ki	0.3162	nM	CHEMBL1258907
9.50	Ki	0.3162	nM	CHEMBL1289267
9.50	Ki	0.3162	nM	CHEMBL1289386
9.50	Ki	0.3162	nM	CHEMBL1290037
9.40	Ki	0.4	nM	CHEMBL4284905
9.40	Ki	0.3981	nM	CHEMBL4284905
9.40	Ki	0.4	nM	CHEMBL403414
9.40	Ki	0.3981	nM	CHEMBL1209159
9.40	Ki	0.3981	nM	CHEMBL1289609
9.40	IC50	0.4	nM	CHEMBL137378
9.40	IC50	0.4	nM	CHEMBL445328
9.33	IC50	0.47	nM	CHEMBL62166
9.30	Ki	0.5	nM	CHEMBL2013012
9.30	Ki	0.5	nM	CHEMBL4281479
9.30	Ki	0.5012	nM	CHEMBL4281479
9.30	IC50	0.5	nM	CHEMBL78089
9.30	IC50	0.5	nM	CHEMBL343318
9.30	IC50	0.5	nM	CHEMBL137449
9.27	IC50	0.54	nM	CHEMBL167991
9.24	IC50	0.57	nM	CHEMBL495169

PubChem BioAssay actives

1378 with measured affinity, of 1869 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
8-[[[1-(2-fluorophenyl)pyrazol-3-yl]amino]methyl]-3-pyridin-2-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	<0.0001	uM
8-[[[5-(2-fluorophenyl)pyrazin-2-yl]amino]methyl]-3-pyridin-2-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	<0.0001	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-pyrimidin-5-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	<0.0001	uM
6-(3-chlorophenyl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0001	uM
2-methyl-4-piperidin-1-yl-6-(3,4,5-trifluorophenyl)-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0001	uM
6-(4-chlorophenyl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0001	uM
2-methyl-4-piperidin-1-yl-6-[3-(trifluoromethyl)phenyl]-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0001	uM
6-(3,4-difluorophenyl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0001	uM
1-[1-(4-fluorophenyl)propan-2-yl]-1-methyl-3-(4-phenoxyphenyl)urea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
3-(9-ethylcarbazol-3-yl)-1-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]-1-methylurea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
3-[4-(4-fluorophenoxy)phenyl]-1-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]-1-methylurea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
3-[4-(3,4-dimethylphenoxy)phenyl]-1-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]-1-methylurea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
1-[1-(4-methoxyphenyl)propan-2-yl]-1-methyl-3-(4-phenoxyphenyl)urea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
3-[4-(N-ethylanilino)phenyl]-1-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]-1-methylurea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
1-methyl-3-(4-phenoxyphenyl)-1-(1-phenylbutan-2-yl)urea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
3-(4-benzylphenyl)-1-[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]-1-methylurea	146054: Inhibitory activity tested against Human Neuropeptide Y5 Receptor.	ic50	0.0001	uM
3-pyridin-2-yl-8-[[(4-pyridin-2-yl-1,3-thiazol-2-yl)amino]methyl]-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[6-(2-fluorophenyl)pyridazin-3-yl]amino]methyl]-3-pyridin-2-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[6-(3,5-difluorophenyl)pyridazin-3-yl]amino]methyl]-3-pyridazin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[6-(2-methylphenyl)pyridazin-3-yl]amino]methyl]-3-pyridazin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
3-pyridin-2-yl-8-[[[5-(1,3-thiazol-2-yl)-2-pyridinyl]amino]methyl]-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-pyrazin-2-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-pyridin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-(2-fluoro-3-pyridinyl)-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-pyridazin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0001	uM
N-(4-chloronaphthalen-1-yl)-1-[2-(5-chloro-2-oxo-1,3-benzothiazol-3-yl)acetyl]piperidine-4-carboxamide	146754: Tested for the inhibition of [125I]PYY binding to HEK 293 cells stably expressed with human neuropeptide NPY Y5 receptor	ic50	0.0002	uM
2-methyl-6-pentyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0002	uM
N-(3,4-dichlorophenyl)-1-methylsulfonylspiro[2H-indole-3,4’-piperidine]-1’-carboxamide	418995: Displacement of [125I]PYY from human recombinant Y5 receptor expressed in mouse LMtk cells	ic50	0.0002	uM
8-[6-(4-fluorophenyl)-1H-benzimidazol-2-yl]-3-phenyl-1-oxa-3,8-diazaspiro[4.5]decan-2-one	538433: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay	ki	0.0002	uM
3-phenyl-8-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one	538433: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay	ki	0.0002	uM
3-pyridin-2-yl-8-[[(5-pyrimidin-2-yl-2-pyridinyl)amino]methyl]-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0002	uM
8-[[(5-cyclobutyloxy-2-pyridinyl)amino]methyl]-3-pyridin-2-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0002	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-pyridazin-4-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0002	uM
8-[[[1-(2-fluorophenyl)pyrazol-4-yl]amino]methyl]-3-(5-methyl-1,3,4-thiadiazol-2-yl)-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0002	uM
8-[[[6-(2-fluorophenyl)pyridazin-3-yl]amino]methyl]-3-pyridazin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0002	uM
6-(1-benzofuran-2-yl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0003	uM
6-(4-fluorophenyl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0003	uM
6-(3-fluorophenyl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0003	uM
3-phenyl-8-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1-oxa-3-azaspiro[4.5]decan-2-one	538433: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay	ki	0.0003	uM
3-(4-fluorophenyl)-8-[6-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1-oxa-3-azaspiro[4.5]decan-2-one	538433: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay	ki	0.0003	uM
2-(2-oxo-3-phenyl-1-oxa-3-azaspiro[4.5]decan-8-yl)-3H-benzimidazole-5-carbonitrile	538433: Antagonistic activity at human NPY Y5 receptor expressed in HEK293 cells assessed as inhibition of calcium level by FLIPR assay	ki	0.0003	uM
8-[[[5-(2-fluorophenyl)pyrimidin-2-yl]amino]methyl]-3-pyridin-2-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0003	uM
8-[[[5-(3-fluoro-2-pyridinyl)-2-pyridinyl]amino]methyl]-3-pyridazin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0003	uM
8-[[[5-(6-methyl-2-pyridinyl)-2-pyridinyl]amino]methyl]-3-pyridazin-3-yl-1-oxa-3-azaspiro[4.5]decan-2-one	517111: Antagonist activity at human NPY Y5 receptor	ki	0.0003	uM
N-[9-(2-methylpropyl)carbazol-3-yl]-3-pyrrolidin-1-ylpropanamide	146884: Binding affinity towards human neuropeptide Y receptor type 5 using 125[I]-PYY as radioligand	ki	0.0003	uM
2-(7-chloro-3-oxo-1,4-benzoxazin-4-yl)-N-[4-[(propan-2-ylsulfonylamino)methyl]cyclohexyl]acetamide	654582: Displacement of [125I]peptide YY from human NPY5 receptor	ki	0.0003	uM
2-(5-chloroindol-1-yl)-N-[4-[(propan-2-ylsulfonylamino)methyl]cyclohexyl]acetamide	654582: Displacement of [125I]peptide YY from human NPY5 receptor	ki	0.0003	uM
4-(3,6-dihydro-2H-pyridin-1-yl)-2-methyl-6-phenyl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0004	uM
3-[4-(3,5-difluorophenyl)phenyl]-1-methyl-1-(1-methylsulfonylpiperidin-4-yl)urea	319998: Displacement of [125]PYY from human chimeric NPY Y5 receptor expressed in CHOK1 cells	ki	0.0004	uM
6-(3,5-difluorophenyl)-2-methyl-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine	146432: Affinity for human neuropeptide Y receptor Y5, binding was evaluated in an in vitro radioligand [125I]PYY binding assay	ic50	0.0004	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	4
methyleugenol	increases expression	1
quercitrin	increases expression	1
trichostatin A	increases expression, decreases expression	1
benzimidazolone	affects binding, decreases activity	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Folic Acid	decreases expression	1
N-Nitrosopyrrolidine	increases expression	1
Rotenone	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1
2-Naphthylamine	decreases activity, affects binding	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

132 unique, capped per target: 96 binding, 36 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001157	Binding	Binding affinity to human NPY Y5 receptor transfected in mouse LMtk cells	Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4’-piperidin]-1’-yl}benzimidazole derivatives. — Bioorg Med Chem Lett
CHEMBL1001164	Functional	Antagonist activity at human NPY Y5 receptor transfected in mouse LMtk cells assessed as inhibition of neuropeptide Y-induced increase in intercellular Ca2+ level	Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4’-piperidin]-1’-yl}benzimidazole derivatives. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TA	ACTOne NPY5R	Transformed cell line	Female
CVCL_ZL01	Tango NPY5R-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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