NPY1R

Summary

NPY1R (neuropeptide Y receptor Y1, HGNC:7956) is a protein-coding gene on chromosome 4q32.2, encoding Neuropeptide Y receptor type 1 (P25929). Receptor for neuropeptide Y and peptide YY.

This gene belongs to the G-protein-coupled receptor superfamily. The encoded transmembrane protein mediates the function of neuropeptide Y (NPY), a neurotransmitter, and peptide YY (PYY), a gastrointestinal hormone. The encoded receptor undergoes fast agonist-induced internalization through clathrin-coated pits and is subsequently recycled back to the cell membrane. Activation of Y1 receptors may result in mobilization of intracellular calcium and inhibition of adenylate cyclase activity.

Source: NCBI Gene 4886 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 37 total
• Druggable target: yes — 32 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7956
Approved symbol	NPY1R
Name	neuropeptide Y receptor Y1
Location	4q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164128
Ensembl biotype	protein_coding
OMIM	162641
Entrez	4886

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000296533, ENST00000504391, ENST00000504790, ENST00000509586, ENST00000511901, ENST00000512819, ENST00000515701, ENST00000875543, ENST00000875544, ENST00000916224, ENST00000916225, ENST00000916226, ENST00000967840, ENST00000967841

RefSeq mRNA: 1 — MANE Select: NM_000909 NM_000909

CCDS: CCDS34089

Canonical transcript exons

ENST00000296533 — 3 exons

Exon	Start	End
ENSE00001081704	163323962	163325758
ENSE00001081706	163325856	163326705
ENSE00001278526	163332482	163332596

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 95.83.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6463 / max 364.4302, expressed in 391 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54665	3.2201	380
54667	0.1408	89
54664	0.1327	90
54666	0.0610	18
54669	0.0591	37
54668	0.0327	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	95.83	silver quality
spleen	UBERON:0002106	94.89	gold quality
metanephros cortex	UBERON:0010533	93.35	gold quality
popliteal artery	UBERON:0002250	93.22	gold quality
tibial artery	UBERON:0007610	93.22	gold quality
right adrenal gland cortex	UBERON:0035827	92.52	gold quality
left adrenal gland cortex	UBERON:0035825	91.76	gold quality
aorta	UBERON:0000947	91.41	gold quality
artery	UBERON:0001637	91.34	gold quality
left adrenal gland	UBERON:0001234	91.13	gold quality
adrenal cortex	UBERON:0001235	91.12	gold quality
right adrenal gland	UBERON:0001233	90.88	gold quality
descending thoracic aorta	UBERON:0002345	90.68	gold quality
adipose tissue	UBERON:0001013	90.04	gold quality
germinal epithelium of ovary	UBERON:0001304	89.69	silver quality
superficial temporal artery	UBERON:0001614	89.53	silver quality
subcutaneous adipose tissue	UBERON:0002190	89.38	gold quality
thoracic aorta	UBERON:0001515	89.26	gold quality
adrenal gland	UBERON:0002369	89.19	gold quality
ascending aorta	UBERON:0001496	88.97	gold quality
connective tissue	UBERON:0002384	88.28	gold quality
body of pancreas	UBERON:0001150	87.44	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.79	gold quality
omental fat pad	UBERON:0010414	86.43	gold quality
peritoneum	UBERON:0002358	86.38	gold quality
right coronary artery	UBERON:0001625	85.78	gold quality
skin of hip	UBERON:0001554	85.36	gold quality
saphenous vein	UBERON:0007318	84.38	silver quality
thoracic mammary gland	UBERON:0005200	84.10	gold quality
mammary gland	UBERON:0001911	83.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	49.12
E-ANND-3	yes	4.13
E-MTAB-5061	no	190.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1

miRNA regulators (miRDB)

104 targeting NPY1R, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343

Literature-anchored findings (GeneRIF, showing 40)

• the NPY Y(1) receptor induces the expression of CRE containing target genes through the CaM kinase-CREB pathway (PMID:11814622)
• Peptide YY and neuropeptide Y exert their effects through the NPY1 receptors in human colon mucosa. (PMID:11906964)
• human NPY Y1 and NPY Y2 receptors were detected in cerebral, meningeal, and coronary arteries using reverse transcriptase-polymerase chain reaction (RT-PCR); in addition, the trigeminal and superior cervical ganglia were positive for both receptors (PMID:12084524)
• Expression of Y1 receptors characterize reactive and proliferating glial cells of diseased retina and may be involved in proliferation of injured glial cells causing regrowth of vitreoretinopathy membranes and consequent secondary retinal detachments. (PMID:12203398)
• a study of ligand-receptor interactions (review) (PMID:12209475)
• High expression of neuropeptide Y receptor Y1 is associated with tumors of the human adrenal gland and extra-adrenal paraganglia (PMID:15623622)
• Y1 receptor activation by neuropeptide Y regulates the growth of prostate cancer cells (PMID:16339211)
• Neuropeptide-Y induced endothelial cell migration was mimicked by agonists and fully blocked by antagonists for any specific NPY receptor (NPY1R). (PMID:16891622)
• data suggest that the K374T variant is a rare, nonfunctional polymorphism of the NPY-Y1R gene and that mutations of the highly conserved NPY-Y1R gene do not represent a frequent mechanism underlying human idiopathic central pubertal disorders. (PMID:17140570)
• Ewing sarcoma family of tumors expressed the NPY receptor subtype Y1 on tumor cells in remarkably high incidence (PMID:18698022)
• ICL3 stabilizes the Y1 receptor in the inactive state and confers structural properties critical for regulating Y receptor activation and signal transduction (PMID:18812316)
• The increased expression of NPY Y1 receptor may be related to local blood flow reduction and structural changes of pelvic supporting tissue in patients with pelvic organ prolapse. (PMID:18953866)
• Results suggest that rabbit and human Y1, Y2 and Y5 receptor subtypes are well conserved, whereas Y4 receptors are less well conserved. (PMID:19481128)
• the studied LEP, NPY1R and GPR54 variants do not have a major influence upon pubertal timing in Caucasian women. (PMID:19506390)
• Genotypic distribution of the NPY1R gene showed a significant association with methamphetamine dependence and psychosis (P = 0.04), whereas the NPY gene had no significant association with them. (PMID:19566775)
• Data suggest that neuropeptide Y modulates steroid production through Y1 receptors in human adrenal H295R cells. (PMID:19699258)
• novel pathophysiological links between the NPY1R locus, autonomic activity, and blood pressure (PMID:19712806)
• NPY1R and NPY5R have roles in nutrient-specific food intake in Europeans (PMID:19759915)
• results suggest that the receptor-ligand interactions have changed during evolution after Y1 and Y2 arose from a common ancestral receptor (PMID:20471432)
• A C-terminal tyrosine-based motif is critical for the constitutive internalization of Y(1) receptors lacking the last 32 C-terminal amino acids. (PMID:20837140)
• neuropeptide Y1 and Y2 receptors were expressed in 33 percent of testicular tumors and Y1 on intratumoral blood vessels in 50 percent of testicular tumors (PMID:21295110)
• Npy1 receptor transgene overexpression is associated with modest anxiolytic-like effect on mice in the open field and elevated plus maze tests. (PMID:21971867)
• For the first time we report a significant association between nicotine dependence and DRD5, NPY1R MAP3K4 single nucleotide polymorphism. (PMID:22309839)
• The influence of beta-arrestin adaptors and endocytosis mechanisms on plasma membrane diffusion and particle brightness of GFP-tagged neuropeptide Y (NPY) receptors, was investigated. (PMID:22487268)
• Y1R expression in visceral adipose tissue might be an indicator of increased risk of metabolic syndrome. (PMID:23838112)
• NPY and its Y receptor are possible mediators of both vasoconstriction and pulmonary vascular remodelling in pulmonary hypertension (PMID:24779394)
• MAPK activation by NPY Y1 receptors is an internalization-independent pathway and that this receptor can transactivate the IGFR receptor. (PMID:25817573)
• Report design of argininamide-type NPY1R antagonists. (PMID:25884646)
• NPY1R plays an inhibitory role in tumor growth and may be a promising therapeutic target for Hepatocellular carcinoma (PMID:27262566)
• expressed in to B and T lymphocytes and mast cells in infantile hemangiomas (PMID:27889920)
• the current review aims to compile, evaluate and summarise current knowledge on PYY, with particular emphasis on obesity and diabetes treatment, and the importance of specific Y receptor interactions for this. (PMID:29412828)
• crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 A resolution, respectively (PMID:29670288)
• Further evidence for the association of GAL, GALR1 and NPY1R variants with opioid dependence. (PMID:32757697)
• Strategic Aspects of NPY-Based Monoclonal Antibodies for Diagnosis and Treatment of Breast Cancer. (PMID:32951575)
• Clinical Significance of Immunohistochemical Expression of Neuropeptide Y1 Receptor in Patients With Breast Cancer in Egypt. (PMID:33086223)
• Theoretical study of the interactions between peptide tyrosine tyrosine [PYY (1-36)], a newly identified modulator in type 2 diabetes pathophysiology, with receptors NPY1R and NPY4R. (PMID:33782920)
• Differential regulation of NPY and SP receptor expression in STRO-1+ve PDLSCs by inflammatory cytokines. (PMID:34773642)
• Expression of hypoxia inducible factor-dependent neuropeptide Y receptors Y1 and Y5 sensitizes hypoxic cells to NPY stimulation. (PMID:35093384)
• NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer. (PMID:35121782)
• Structural basis of neuropeptide Y signaling through Y1 receptor. (PMID:35165283)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	npy1r	ENSDARG00000037411
mus_musculus	Npy1r	ENSMUSG00000036437
rattus_norvegicus	Npy1r	ENSRNOG00000014149

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

Neuropeptide Y receptor type 1 — P25929 (reviewed: P25929)

All UniProt accessions (7): B4DKL9, D6R9D0, D6RC44, D6REY0, D6RHH6, D6RI97, P25929

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_000900* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000351	NPY1_rcpt	Family
IPR000611	NPY_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (43 total): helix 13, topological domain 8, transmembrane region 7, strand 4, glycosylation site 3, turn 2, chain 1, modified residue 1, lipid moiety-binding region 1, disulfide bond 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5ZBQ	X-RAY DIFFRACTION	2.7
5ZBH	X-RAY DIFFRACTION	3
7VGX	ELECTRON MICROSCOPY	3.2
7X9A	ELECTRON MICROSCOPY	3.2
8K6M	ELECTRON MICROSCOPY	3.3
8K6O	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25929-F1	79.70	0.55

Antibody-complex structures (SAbDab): 3 — 7VGX, 8K6M, 8K6O

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 (2): 368, 338

Disulfide bonds (1): 113–198

Glycosylation sites (3): 2, 11, 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: 200 (showing top): BENPORATH_ES_WITH_H3K27ME3, chr4q32, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, STAEGE_EWING_FAMILY_TUMOR, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, MODULE_64, GOBP_GROWTH, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, SMID_BREAST_CANCER_ERBB2_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_PAIN, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS

GO Biological Process (14): outflow tract morphogenesis (GO:0003151), glucose metabolic process (GO:0006006), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), locomotory behavior (GO:0007626), feeding behavior (GO:0007631), regulation of blood pressure (GO:0008217), sensory perception of pain (GO:0019233), regulation of multicellular organism growth (GO:0040014), cell communication (GO:0007154), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), signaling (GO:0023052)

GO Molecular Function (7): peptide YY receptor activity (GO:0001601), pancreatic polypeptide receptor activity (GO:0001602), neuropeptide Y receptor activity (GO:0004983), neuropeptide receptor activity (GO:0008188), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), neuron projection (GO:0043005), 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
G protein-coupled receptor signaling pathway	3
behavior	2
cellular process	2
neuropeptide Y receptor activity	2
heart morphogenesis	1
anatomical structure morphogenesis	1
hexose metabolic process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
blood circulation	1
regulation of biological quality	1
sensory perception	1
multicellular organism growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological process	1
neuropeptide receptor activity	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
peptide binding	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPY1R	NPY	P01303	999
NPY1R	PYY	P10082	933
NPY1R	GHRL	Q9UBU3	786
NPY1R	QRFP	P83859	746
NPY1R	PPY	P01298	733
NPY1R	AGRP	O00253	722
NPY1R	GAL	P22466	679
NPY1R	PRLH	P81277	664
NPY1R	MC4R	P32245	663
NPY1R	NPFF	O15130	594
NPY1R	POMC	P01189	578
NPY1R	TAC1	P20366	572
NPY1R	NPY5R	Q15761	549
NPY1R	HCRT	O43612	511
NPY1R	LGALS2	P05162	508

IntAct

8 interactions, top by confidence:

A	B	Type	Score
NPY1R	NPY	psi-mi:“MI:0915”(physical association)	0.400
PYY	NPY1R	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	NPY1R	psi-mi:“MI:0915”(physical association)	0.400
NPY1R	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
NPY1R	ATP13A2	psi-mi:“MI:0915”(physical association)	0.370
NPY1R	GALR2	psi-mi:“MI:2364”(proximity)	0.270
LSM7	NPY1R	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): NPY1R (Two-hybrid), NPY1R (Reconstituted Complex), NPY1R (Two-hybrid)

ESM2 similar proteins: O02813, O02835, O02836, O43614, O62809, O93603, P0C0L6, P0DQD5, P21555, P21761, P25929, P28647, P30731, P34981, P34992, P35382, P47751, P49146, P50391, P56719, P58308, P70031, P79113, P79217, P79945, P97295, Q04573, Q1RMU8, Q28596, Q56H79, Q5IS62, Q61041, Q61212, Q61618, Q63447, Q6W5P4, Q8BZP8, Q8K458, Q8NFJ6, Q8SPN1

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

1 interactions.

A	Effect	B	Mechanism
NPY	up-regulates	NPY1R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

610 predictions. Top by Δscore:

Variant	Effect	Δscore
4:163331788:C:A	donor_gain	0.9800
4:163332480:AC:A	donor_gain	0.9800
4:163332481:CC:C	donor_gain	0.9800
4:163332481:CCCT:C	donor_gain	0.9800
4:163332619:T:TA	donor_gain	0.9800
4:163344134:G:GT	donor_gain	0.9800
4:163326706:C:CC	acceptor_gain	0.9700
4:163332583:AGAT:A	donor_gain	0.9700
4:163344000:GGT:G	donor_loss	0.9700
4:163344001:GTACG:G	donor_loss	0.9700
4:163344002:T:G	donor_loss	0.9700
4:163326702:CAAT:C	acceptor_gain	0.9600
4:163326704:ATC:A	acceptor_loss	0.9300
4:163326705:TCT:T	acceptor_loss	0.9300
4:163326706:CTGTA:C	acceptor_loss	0.9300
4:163326707:T:G	acceptor_loss	0.9300
4:163332477:CTT:C	donor_loss	0.9300
4:163332478:TTAC:T	donor_loss	0.9300
4:163332479:TA:T	donor_loss	0.9300
4:163332480:A:AG	donor_loss	0.9300
4:163344339:A:T	donor_gain	0.9200
4:163326708:G:C	acceptor_loss	0.9100
4:163331951:TCC:T	donor_gain	0.9100
4:163331952:CCC:C	donor_gain	0.9100
4:163332480:A:AC	donor_gain	0.9100
4:163332481:C:CC	donor_gain	0.9100
4:163332634:TC:T	donor_gain	0.9100
4:163332635:CC:C	donor_gain	0.9100
4:163332336:TGCG:T	donor_gain	0.9000
4:163343998:GAG:G	donor_gain	0.9000

AlphaMissense

2582 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:163325496:C:T	G321E	0.999
4:163325642:A:C	F272L	0.999
4:163325642:A:T	F272L	0.999
4:163325644:A:G	F272L	0.999
4:163326068:A:G	W163R	0.999
4:163326068:A:T	W163R	0.999
4:163326133:A:G	L141P	0.999
4:163326142:C:G	R138P	0.999
4:163326151:G:T	A135D	0.999
4:163326237:C:A	W106C	0.999
4:163326237:C:G	W106C	0.999
4:163326310:A:G	L82P	0.999
4:163326312:G:C	N81K	0.999
4:163326312:G:T	N81K	0.999
4:163325508:G:C	P317R	0.998
4:163325508:G:T	P317H	0.998
4:163325532:G:T	A309E	0.998
4:163325625:G:C	P278R	0.998
4:163325632:A:G	W276R	0.998
4:163325632:A:T	W276R	0.998
4:163325664:A:G	L265P	0.998
4:163326136:T:G	Q140P	0.998
4:163326152:C:G	A135P	0.998
4:163326163:A:G	L131P	0.998
4:163326239:A:G	W106R	0.998
4:163326239:A:T	W106R	0.998
4:163326298:T:A	D86V	0.998
4:163326298:T:G	D86A	0.998
4:163326319:A:T	I79N	0.998
4:163326322:A:G	L78P	0.998

dbSNP variants (sampled 300 via entrez): RS1000116856 (4:163325019 T>C), RS1000175280 (4:163345554 T>C,G), RS1000210239 (4:163338318 T>G), RS1000387640 (4:163332190 G>T), RS1000438912 (4:163345196 A>C), RS1000593981 (4:163324873 G>A,T), RS1000686795 (4:163338525 T>G), RS1000699637 (4:163332170 T>A), RS1001010596 (4:163344647 C>A,T), RS1001279666 (4:163333386 C>A), RS1001280685 (4:163337331 G>A), RS1001439226 (4:163343882 C>G), RS1001441794 (4:163344904 C>G,T), RS1001557579 (4:163323481 C>A,T), RS1001675384 (4:163330445 C>A)

Disease associations

OMIM: gene MIM:162641 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003449_3	Erythrocyte cadmium concentration	8.000000e-06
GCST004748_41	Lung cancer	9.000000e-06
GCST006436_9	Triglyceride levels	1.000000e-10
GCST009391_1393	Metabolite levels	7.000000e-06
GCST011494_98	Daytime nap	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4777 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

32 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 635,729 (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
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1201049	ECONAZOLE NITRATE	4	3,918
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1219	RABEPRAZOLE	4	12,441
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL1651990	FENTICONAZOLE	4	8,940
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL2062335	METOPROLOL TARTRATE	4	55
CHEMBL328190	LASOFOXIFENE	4	10,617
CHEMBL374478	RIFAMPIN	4	93,834
CHEMBL422	TRIFLUOPERAZINE	4	20,044
CHEMBL43	AMSACRINE	4	82,326
CHEMBL434394	NEBIVOLOL	4	9,645
CHEMBL479	THIORIDAZINE	4	21,859
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL535	SUNITINIB	4	79,020
CHEMBL58	MITOXANTRONE	4	166,878
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL723	CARVEDILOL	4
CHEMBL76370	TEGASEROD	4
CHEMBL790	CHLORHEXIDINE	4
CHEMBL83	TAMOXIFEN	4
CHEMBL1096979	BENSERAZIDE	3
CHEMBL2103773	OTILONIUM BROMIDE	3
CHEMBL273264	NAFAMOSTAT	3
CHEMBL1182210	BENZETHONIUM	2
CHEMBL1187011	DOMIPHEN	2
CHEMBL4540843	PANCREATIC POLYPEPTIDE	2

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 (25 total), top 25:

Ligand	Action	Affinity	Parameter
GR231118	Antagonist	10.9	pKi
peptide YY	Full agonist	10.2	pKi
[125I]PYY (pig)	Full agonist	10.2	pKd
[125I]GR231118	Antagonist	10.0	pKd
NPY	Full agonist	9.7	pKi
BIBO3304	Antagonist	9.5	pIC50
BIBP3226	Antagonist	9.33	pKi
[125I]NPY (human, mouse, rat)	Full agonist	9.2	pKd
NPY-(2-36)	Full agonist	9.2	pKi
[3H]NPY (human, mouse, rat)	Full agonist	8.8	pKd
[3H]BIBP3226	Antagonist	8.7	pKd
BMS-193885	Antagonist	8.48	pKd
[Leu31,Pro34]NPY (pig)	Full agonist	8.4	pIC50
SR120819A	Antagonist	8.4	pKi
pancreatic polypeptide	Full agonist	7.9	pKi
NPY-(13-36) (pig)	Full agonist	7.8	pKi
NPY-(3-36) (pig)	Full agonist	7.7	pKi
PYY-(13-36) (mouse, rat, pig)	Full agonist	7.5	pKi
PYY-(3-36)	Full agonist	7.4	pKi
[Leu31,Pro34]PYY (pig)	Full agonist	7.4	pIC50
[Leu31,Pro34]NPY	Agonist	7.1	pEC50
pancreatic polypeptide	Full agonist	7.0	pKi
NPY-(2-36) (pig)	Full agonist	6.3	pIC50
[Ala31,Aib32]NPY (pig)	Full agonist	6.0	pIC50

Binding affinities (BindingDB)

56 measured of 141 human assays (151 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NPY, porcine	KI	0.07 nM
P34-PYY,human	KI	0.14 nM
PYY Pro34, Human	KI	0.14 nM
CAS_118997-30-1	KI	0.17 nM
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
[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
NPY16-36, porcine	KI	41 nM
PP [Ile31,Gln34], human	KI	42.7 nM
PYY3-36, human	KI	45.7 nM
A single isomer of 2,2’,2″-(10-(2-((2-(2-(3-(4-((4R,Z)-9-amino-4-((2,6-difluoro-4-hydroxybenzyl)carbamoyl)-1-(isoindolin-2-yl)-2,11,16-trioxo-3,8,10,12,15-pentaazaoctadec-9-en-1-yl)phenyl)propoxy)ethoxy)ethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(R)—N-(4-hydroxybenzyl)-2-((R)-2-(isoindolin-2-yl)-2-phenylacetamido)-5-((Z)-2-((2-propionamidoethyl)carbamoyl)guanidino)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(R)-2-((R)-2-(4-(3-aminopropoxy)phenyl)-2-(isoindolin-2-yl)acetamido)-N-(4-hydroxybenzyl)-5-((Z)-2-((2-propionamidoethyl)carbamoyl)guanidinopentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-(isoindolin-2-yl)-2-phenylacetamido)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
US20250213735, Compound 70	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-(4-isopropylpiperidin-1-yl)-2-phenylacetamido)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-(2-(4-ethylpiperidin-1-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-(2-(4-(tert-butyl)piperidin-1-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(6-azaspiro[2.5]octan-6-yl)acetamido)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(7-azaspiro[3.5]nonan-7-yl)acetamido)pentanamide	KI	55 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
NPY, C2	KI	72.4 nM
CAS_59763-91-6	KI	97.7 nM
PP2-36, HUMAN	KI	100 nM
PP13-36, HUMAN	KI	100 nM
CAS_59763-91-6	KI	170 nM
CAS_59763-91-6	KI	209 nM
NPY, free acid, human	KI	398 nM
NSC_41735	KI	468 nM
PP [cPP(1-7), NPY(19-23), Ala31, Aib32, Gln34], human	KI	530 nM
2,2’,2″-(10-(2-((6-((3-(4-((1R,4R,Z)-9-amino-4-((4-hydroxybenzyl)carbamoyl)-1-(isoindolin-2-yl)-2,11,16-trioxo-3,8,10,12,15-pentaazaoctadec-9-en-1-yl)phenoxy)propyl)-amino)-6-oxohexyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid-2,2,2-trifluoroacetic acid (1/1)	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(piperidin-1-yl)acetamido)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(4-(trifluoromethyl)piperidin-1-yl)acetamido)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-(2-(4,4-dimethylpiperidin-1-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-(2-(3,3-dimethylpiperidin-1-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(R)-5-guanidino-N-(4-hydroxybenzyl)-2-((S)-2-phenyl-2-(4-propylpiperidin-1-yl)acetamidlentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-(2-(4-cyclopropylpiperidin-1-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-(4-isobutylpiperidin-1-yl)-2-phenylacetamido)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(8-azaspiro[4.5]decan-8-yl)acetamido)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(4-phenylpiperidin-1-yl)acetamido)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-5-guanidino-N-(4-hydroxybenzyl)-2-(2-phenyl-2-(3-azaspiro[5.5]undecan-3-yl)acetamido)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-((2S)-2-(6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
(2R)-2-(2-(2,2-difluoro-7-azaspiro[3.5]nonan-7-yl)-2-phenylacetamido)-5-guanidino-N-(4-hydroxybenzyl)pentanamide	KI	550 nM	US-20250213735: NEUROPEPTIDE Y1 RECEPTOR (NPY1R) TARGETED THERAPEUTICS AND USES THEREOF
NPY [Ala31, Aib32], porcine	KI	700 nM

ChEMBL bioactivities

1129 potent at pChembl≥5 of 1268 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL269503
10.59	Kd	0.026	nM	CHEMBL3747715
10.50	Ki	0.03162	nM	CHEMBL4746035
10.43	Ki	0.037	nM	CHEMBL508974
10.40	Kd	0.04	nM	CHEMBL3747715
10.40	EC50	0.03981	nM	CHEMBL3559801
10.36	Kd	0.044	nM	CHEMBL3747715
10.32	Kd	0.048	nM	CHEMBL3747715
10.32	EC50	0.0476	nM	CHEMBL5420881
10.30	IC50	0.05012	nM	CHEMBL508974
10.28	Ki	0.05248	nM	CHEMBL4794692
10.28	Ki	0.052	nM	CHEMBL349328
10.26	IC50	0.05495	nM	CHEMBL4746035
10.23	Ki	0.05888	nM	CHEMBL4743976
10.22	Ki	0.06	nM	CHEMBL511460
10.22	Ki	0.06	nM	CHEMBL508974
10.21	IC50	0.06166	nM	CHEMBL4786911
10.20	IC50	0.0631	nM	CHEMBL508974
10.20	Ki	0.0631	nM	CHEMBL4762668
10.18	IC50	0.06607	nM	CHEMBL4755692
10.17	Ki	0.06761	nM	CHEMBL4743858
10.15	Ki	0.07	nM	CHEMBL2110365
10.15	IC50	0.07	nM	HUMAN NEUROPEPTIDE Y
10.15	Ki	0.07079	nM	CHEMBL4751322
10.13	Kd	0.074	nM	CHEMBL3747715
10.13	Ki	0.07413	nM	CHEMBL4752392
10.11	Ki	0.077	nM	CHEMBL3746386
10.10	IC50	0.07943	nM	CHEMBL4794692
10.08	Kd	0.083	nM	CHEMBL3747715
10.04	IC50	0.0912	nM	CHEMBL4798118
10.02	Ki	0.096	nM	HUMAN NEUROPEPTIDE Y
10.00	IC50	0.1	nM	CHEMBL511460
10.00	IC50	0.1	nM	CHEMBL3746870
10.00	IC50	0.1	nM	CHEMBL3746386
10.00	Ki	0.1	nM	CHEMBL3746386
10.00	EC50	0.1	nM	CHEMBL4281479
10.00	Ki	0.1	nM	CHEMBL511460
10.00	Ki	0.1	nM	CHEMBL508974
9.98	IC50	0.1047	nM	CHEMBL3746870
9.97	Ki	0.106	nM	CHEMBL155802
9.96	IC50	0.1096	nM	CHEMBL4743858
9.95	Ki	0.1122	nM	CHEMBL4753520
9.95	Ki	0.112	nM	CHEMBL347807
9.92	IC50	0.1202	nM	CHEMBL511460
9.92	Ki	0.12	nM	CHEMBL508974
9.92	Ki	0.12	nM	NEUROPEPTIDE-Y
9.90	IC50	0.1259	nM	CHEMBL508974
9.90	Ki	0.1259	nM	CHEMBL4281479
9.90	Ki	0.1259	nM	CHEMBL4786911
9.90	IC50	0.1259	nM	CHEMBL4751322

PubChem BioAssay actives

985 with measured affinity, of 2868 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
ethyl 2-[[N’-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[(4-hydroxyphenyl)methylamino]-5-oxopentyl]carbamimidoyl]carbamoylamino]acetate	1266474: Displacement of (R)-Na-Diphenylacetyl-Nomega[2-([2,3-3H]-propionylamino)ethyl]aminocarbonyl (4-hydroxybenzyl)-argininamide from NPY1R in human SK-N-MC cells by radioligand binding assay	ki	<0.0001	uM
(2R)-5-[[amino-[2-(2,3-ditritiopropanoylamino)ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide	1266482: Binding affinity to NPY1R in human SK-N-MC cells after 90 mins	kd	<0.0001	uM
2-(4-tert-butylphenoxy)cyclohexan-1-ol	1450959: Positive allosteric modulation of human C-terminal eYFP-fused human NY1 receptor expressed in African green monkey COS7 cells co-expressing delta6Galphaqi4-myr assessed as potentiation of neuropeptide Y-mediated Ca2+ flux by measuring pancreatic polypeptide EC50 at 30 uM treated at 20 secs post baseline detection followed by addition of neuropeptide Y after 140 secs by Fluo2-AM fluorescent dye-based assay (Rvb = 10.3 +/- 0.1 No_unit)	ec50	<0.0001	uM
(2R)-5-[[amino-[2-[(2-fluoroacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	<0.0001	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid	146430: Affinity against Neuropeptide Y receptor Y1 in SK-N-MC cell line	ic50	<0.0001	uM
N-[1-methyl-2-oxo-5-(pyrrolidine-1-carbonyl)-3-pyridinyl]-2-(2-methylphenoxy)acetamide	1981607: Positive allosteric modulation of YFP tagged human Y1 receptor transfected with COS-7 cells co-transfected with delta6Galphaqi4-myr measured after 24 hrs by calcium 2+ flux assay (Rvb = 64.6 pM )	ec50	<0.0001	uM
(2R)-5-[[amino-(ethylcarbamoylamino)methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide	1266457: Displacement of [3H]propionyl-pNPY from NPY1R (unknown origin)	ki	0.0001	uM
ethyl 3-[[N’-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[(4-hydroxyphenyl)methylamino]-5-oxopentyl]carbamimidoyl]carbamoylamino]propanoate	1266464: Antagonist activity at NPY1R in human HEL cells assessed as inhibition of 10 nM pNPY-induced Ca+2 response preincubated for 15 mins by Fura-2 dye based spectrofluorimetric analysis	ic50	0.0001	uM
(2R)-5-[[amino-[2-(propanoylamino)ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;bis(2,2,2-trifluoroacetic acid)	1266465: Antagonist activity at NPY1R in human HEL cells assessed as inhibition of 10 nM pNPY-induced Ca+2 response preincubated for 20 mins by Fura-2 dye based spectrofluorimetric analysis	ic50	0.0001	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid	2198842: Binding affinity to Y1 (unknown origin) assessed as inhibition constant	ki	0.0001	uM
(2R)-5-[[amino-[2-[(2,2-difluoroacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[(2-acetamidoethylcarbamoylamino)-aminomethylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[2-[(2,2,2-trifluoroacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[3-(propanoylamino)propylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[2-(prop-2-enoylamino)ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[2-(2-methylpropanoylamino)ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695029: Antagonist activity at Y1 receptor in human HEL cells assessed as reduction in pNPY-induced calcium mobilization preincubated for 15 mins followed by pNPY stimulation and measured immediately by Fura-2 dye based fluorescence assay	ic50	0.0001	uM
(2R)-5-[[(3-acetamidopropylcarbamoylamino)-aminomethylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[2-[(2-bromoacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[2-[(2-chloroacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(2R)-5-[[amino-[2-[(2-hydroxyacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0001	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid	751870: Binding affinity to human neuropeptide Y receptor type 1 by radioligand displacement assay	ki	0.0001	uM
4-[4-[3-[2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)benzimidazol-1-yl]propyl]piperidin-1-yl]-1-phenylbutan-1-one	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0001	uM
3-[4-[3-[2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)benzimidazol-1-yl]propyl]piperidin-1-yl]-1-phenylpropan-1-one	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0001	uM
2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)-1-[3-[1-(3-piperidin-1-ylpropyl)piperidin-4-yl]propyl]benzimidazole	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0001	uM
6-[[5-ethyl-4-(fluoromethyl)-1,3-thiazol-2-yl]sulfanylmethyl]-N-[(6-methyl-2-pyridinyl)methyl]-4-morpholin-4-ylpyridin-2-amine	447594: Displacement of [125I]-PYY from human NPYY1 receptor overexpressed in CHO cell membrane after 120 mins by scintillation counting	ic50	0.0001	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid	1418829: Displacement of [125I]-PYY(1 to 36 residues) from human Y1R expressed in BHK-21 cell membranes after 2 hrs by scintillation proximity assay	ki	0.0001	uM
(3S,9S,12S,18S,24S,27S)-9-N,24-N-bis[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-3,18-bis[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-2,6,11,17,21,26-hexaoxo-1,7,10,16,22,25-hexazatricyclo[25.3.0.012,16]triacontane-9,24-dicarboxamide	143543: Affinity for cloned Y1 receptor using [125I]PYY as radioligand	ki	0.0001	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494756: Displacement of [125I]peptide YY from human Y1 receptor after 120 mins by scintillation counting analysis	ic50	0.0001	uM
1-[3-[1-[2-(4-iodophenyl)ethyl]piperidin-4-yl]propyl]-2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)benzimidazole	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0001	uM
(2R)-5-[[amino-[(1-methyltriazol-4-yl)methylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1266463: Antagonist activity at NPY1R in human HEL cells assessed as inhibition of 10 nM pNPY-induced Ca+2 response preincubated for 10 mins by Fura-2 dye based spectrofluorimetric analysis	ic50	0.0002	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]-methylamino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid	1418833: Activation of human Y1R expressed in HEK293 cells assessed as inhibition of isoproterenol-induced increase in intracellular cAMP levels by calcium 5 dye-based FLIPR assay	ec50	0.0002	uM
(4S)-4-[[2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1418833: Activation of human Y1R expressed in HEK293 cells assessed as inhibition of isoproterenol-induced increase in intracellular cAMP levels by calcium 5 dye-based FLIPR assay	ec50	0.0002	uM
(4S)-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(3S)-6-amino-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-1-oxopentan-2-yl]amino]-1,6-dioxohexan-3-yl]-methylamino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-aminopropanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid	1418833: Activation of human Y1R expressed in HEK293 cells assessed as inhibition of isoproterenol-induced increase in intracellular cAMP levels by calcium 5 dye-based FLIPR assay	ec50	0.0002	uM
N-[2-[[N’-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[(4-hydroxyphenyl)methylamino]-5-oxopentyl]carbamimidoyl]carbamoylamino]ethyl]cyclopropanecarboxamide;2,2,2-trifluoroacetic acid	1695029: Antagonist activity at Y1 receptor in human HEL cells assessed as reduction in pNPY-induced calcium mobilization preincubated for 15 mins followed by pNPY stimulation and measured immediately by Fura-2 dye based fluorescence assay	ic50	0.0002	uM
(2R)-5-[[amino-[2-[(2-aminoacetyl)amino]ethylcarbamoylamino]methylidene]amino]-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide;2,2,2-trifluoroacetic acid	1695028: Displacement of [3H]UR-MK299 from Y1 receptor in human SK-N-MC cells by radioligand binding assay	ki	0.0002	uM
N-[2-[[N’-[(4R)-4-[(2,2-diphenylacetyl)amino]-5-[(4-hydroxyphenyl)methylamino]-5-oxopentyl]carbamimidoyl]carbamoylamino]ethyl]cyclobutanecarboxamide;2,2,2-trifluoroacetic acid	1695029: Antagonist activity at Y1 receptor in human HEL cells assessed as reduction in pNPY-induced calcium mobilization preincubated for 15 mins followed by pNPY stimulation and measured immediately by Fura-2 dye based fluorescence assay	ic50	0.0002	uM
2-(phenoxymethyl)-1-[3-[1-[(Z)-3-phenylprop-2-enyl]piperidin-4-yl]propyl]-4-(3-piperidin-1-ylpropoxy)benzimidazole	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0002	uM
2-(phenoxymethyl)-1-[3-[1-(2-phenylethyl)piperidin-4-yl]propyl]-4-(3-piperidin-1-ylpropoxy)benzimidazole	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0002	uM
6-[[4-(fluoromethyl)-5-methyl-1,3-thiazol-2-yl]sulfanylmethyl]-N-[(6-methyl-2-pyridinyl)methyl]-4-morpholin-4-ylpyridin-2-amine	447594: Displacement of [125I]-PYY from human NPYY1 receptor overexpressed in CHO cell membrane after 120 mins by scintillation counting	ic50	0.0002	uM
6-[(4,5-dimethyl-1,3-oxazol-2-yl)sulfanylmethyl]-N-[(6-methyl-2-pyridinyl)methyl]-4-thiomorpholin-4-ylpyridin-2-amine	447594: Displacement of [125I]-PYY from human NPYY1 receptor overexpressed in CHO cell membrane after 120 mins by scintillation counting	ic50	0.0002	uM
(3S,9S,12S,18S,24S,27S)-9-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-3,18-bis[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-24-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-2,6,11,17,21,26-hexaoxo-1,7,10,16,22,25-hexazatricyclo[25.3.0.012,16]triacontane-9,24-dicarboxamide	1607554: Displacement of (sCy5)-[Lys2 Arg4]-BVD15 from GFP-tagged Y1R in human HEK293T cells assessed as inhibitory constant incubated for 5 mins followed by (sCy5)-[Lys2 Arg4]-BVD15 addition and measured after 30 mins by fluorescence based assay	ki	0.0003	uM
(3S,9S,12S,18S,24S,27S)-9-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-24-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-3,18-bis[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-2,6,11,17,21,26-hexaoxo-1,7,10,16,22,25-hexazatricyclo[25.3.0.012,16]triacontane-9,24-dicarboxamide	1607554: Displacement of (sCy5)-[Lys2 Arg4]-BVD15 from GFP-tagged Y1R in human HEK293T cells assessed as inhibitory constant incubated for 5 mins followed by (sCy5)-[Lys2 Arg4]-BVD15 addition and measured after 30 mins by fluorescence based assay	ki	0.0003	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(3S,9S,12S,18R,24R,27S)-3,18-bis[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-24-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-3-(4-hydroxyphenyl)-1-methoxy-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]-2,6,11,17,21,26-hexaoxo-1,7,10,16,22,25-hexazatricyclo[25.3.0.012,16]triacontane-9-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	143541: Affinity for cloned Y1 receptor using [125I]PYY as radioligand	ki	0.0003	uM
4-[2-[4-[3-[2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)benzimidazol-1-yl]propyl]piperidin-1-yl]ethyl]phenol	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0003	uM
1-[3-[1-(2-cyclohexylethyl)piperidin-4-yl]propyl]-2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)benzimidazole	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0003	uM
1-[3-[1-(3-methylbutyl)piperidin-4-yl]propyl]-2-(phenoxymethyl)-4-(3-piperidin-1-ylpropoxy)benzimidazole	146580: Ability to displace [125I]-peptide YY binding to cloned human Neuropeptide Y receptor type 1 expressed in AV-12 cells	ki	0.0003	uM
6-[(4,5-dimethyl-1,3-thiazol-2-yl)sulfanylmethyl]-N-[(6-methyl-2-pyridinyl)methyl]-4-morpholin-4-ylpyridin-2-amine	447594: Displacement of [125I]-PYY from human NPYY1 receptor overexpressed in CHO cell membrane after 120 mins by scintillation counting	ic50	0.0003	uM
6-[(4,5-dimethyl-1,3-oxazol-2-yl)sulfanylmethyl]-N-[(6-fluoro-2-pyridinyl)methyl]-4-thiomorpholin-4-ylpyridin-2-amine	447594: Displacement of [125I]-PYY from human NPYY1 receptor overexpressed in CHO cell membrane after 120 mins by scintillation counting	ic50	0.0003	uM
(2R)-N-[[4-[(carbamoylamino)methyl]phenyl]methyl]-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]pentanamide	597411: Displacement of [3H]-UR-MK114 from Y1R in human SK-N-MC cells	ki	0.0003	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3R)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2R)-1-[[(2R)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-1-[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid	1266473: Displacement of (R)-Na-Diphenylacetyl-Nomega[2-([2,3-3H]-propionylamino)ethyl]aminocarbonyl (4-hydroxybenzyl)-argininamide from NPY1R in human SK-N-MC cells preincubated with radioligand followed by protein addition for 60 mins by radioligand binding assay	ki	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	5
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, decreases reaction	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression, increases methylation	2
Coumestrol	increases expression, affects reaction, affects cotreatment	2
Estrogens	decreases reaction, increases expression, affects expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Medroxyprogesterone Acetate	decreases reaction, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	increases expression	1
trichostatin A	decreases expression, increases expression	1
afimoxifene	decreases reaction, increases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
tobacco tar	decreases reaction, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
allyl sulfide	decreases reaction, increases expression	1
neuropeptide Y, Leu(31)-Pro(34)-	increases activity	1
BIBP 3226	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression	1
Cycloheximide	decreases expression, decreases reaction	1

ChEMBL screening assays

317 unique, capped per target: 248 binding, 69 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000189	Binding	Binding affinity to NPY1 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1011811	Functional	Antagonist activity at neuropeptide Y1 receptor in human HEL assessed as change in pNPY-induced calcium response by fura-2-based fluorescence assay	Guanidine-acylguanidine bioisosteric approach in the design of radioligands: synthesis of a tritium-labeled N(G)-propionylargininamide ([3H]-UR-MK114) as a highly potent and selective neuropeptide Y Y1 receptor antagonist. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 spontaneously immortalized cell line, 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0T8	ACTOne NPY1R	Transformed cell line	Female
CVCL_H373	293/NPY1	Transformed cell line	Female
CVCL_H479	CHO-K1/NPY1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KY64	PathHunter CHO-K1 NPY1R beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_U001	CHO-NPY1R	Spontaneously immortalized cell line	Female
CVCL_ZL02	Tango NPY1R-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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