NPFFR1

Summary

NPFFR1 (neuropeptide FF receptor 1, HGNC:17425) is a protein-coding gene on chromosome 10q22.1, encoding Neuropeptide FF receptor 1 (Q9GZQ6). Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides.

Enables neuropeptide receptor activity. Involved in neuropeptide signaling pathway. Located in cilium. Is active in plasma membrane.

Source: NCBI Gene 64106 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 85 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_022146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17425
Approved symbol	NPFFR1
Name	neuropeptide FF receptor 1
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	OT7T022, NPFF1R1
Ensembl gene	ENSG00000148734
Ensembl biotype	protein_coding
OMIM	607448
Entrez	64106

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000277942

RefSeq mRNA: 1 — MANE Select: NM_022146 NM_022146

CCDS: CCDS53539

Canonical transcript exons

ENST00000277942 — 4 exons

Exon	Start	End
ENSE00000987111	70266077	70266391
ENSE00000987113	70260640	70260739
ENSE00002433012	70283670	70284004
ENSE00003583539	70247329	70255827

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 77.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2154 / max 63.4126, expressed in 70 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109832	0.1007	45
109833	0.0866	29
109834	0.0282	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	77.02	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	74.67	silver quality
inferior olivary complex	UBERON:0002127	74.53	gold quality
cervix squamous epithelium	UBERON:0006922	73.43	gold quality
tongue squamous epithelium	UBERON:0006919	73.24	gold quality
cerebellar vermis	UBERON:0004720	71.56	gold quality
cerebellar cortex	UBERON:0002129	71.03	gold quality
cerebellar hemisphere	UBERON:0002245	70.91	gold quality
cerebellum	UBERON:0002037	70.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.53	gold quality
cardia of stomach	UBERON:0001162	69.32	gold quality
olfactory bulb	UBERON:0002264	69.14	gold quality
type B pancreatic cell	CL:0000169	69.05	gold quality
heart right ventricle	UBERON:0002080	69.04	gold quality
triceps brachii	UBERON:0001509	68.85	gold quality
vena cava	UBERON:0004087	68.56	gold quality
saphenous vein	UBERON:0007318	68.52	gold quality
nipple	UBERON:0002030	68.50	gold quality
tongue	UBERON:0001723	68.48	gold quality
subthalamic nucleus	UBERON:0001906	68.44	gold quality
inferior vagus X ganglion	UBERON:0005363	68.41	gold quality
pericardium	UBERON:0002407	68.20	gold quality
ventral tegmental area	UBERON:0002691	68.19	gold quality
superior surface of tongue	UBERON:0007371	68.18	gold quality
body of tongue	UBERON:0011876	68.11	gold quality
pharyngeal mucosa	UBERON:0000355	68.10	gold quality
substantia nigra pars reticulata	UBERON:0001966	68.01	gold quality
lateral globus pallidus	UBERON:0002476	67.96	gold quality
dorsal plus ventral thalamus	UBERON:0001897	67.95	gold quality
substantia nigra pars compacta	UBERON:0001965	67.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.22
E-MTAB-5061	no	1.74

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• GnIH homologs in the human hypothalamus and were identified and human GnIH receptor (GPR147) mRNA expression in the hypothalamus as well as in the pituitary, was characterized. (PMID:20027225)
• In male rats, mRNA expressions of both RFRP and GPR147 increases from postnatal days 12 and 16; mRNA expression of GPR147 in female rats increases from postnatal day 16, peaking at postnatal day 28 and decreasing from postnatal day 35. (PMID:22064075)
• ovarian RFRP-3/GPR147 signaling could contribute to normal ovarian function (PMID:22691551)
• RFRP-3/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out (PMID:25180599)
• Effects of systematic N-terminus deletions and benzoylations of endogenous RF-amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103. (PMID:26211894)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	npffr1	ENSDARG00000111997
mus_musculus	Npffr1	ENSMUSG00000020090
rattus_norvegicus	Npffr1	ENSRNOG00000000559
drosophila_melanogaster	SIFaR	FBGN0038880

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), AVPR2 (ENSG00000126895), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Protein

Protein identifiers

Neuropeptide FF receptor 1 — Q9GZQ6 (reviewed: Q9GZQ6)

Alternative names: G-protein coupled receptor 147, RFamide-related peptide receptor OT7T022

All UniProt accessions (1): Q9GZQ6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_071429* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR005395	NPFF_rcpt	Family
IPR005396	NPFF_rcpt_1	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (28 total): topological domain 8, transmembrane region 7, glycosylation site 5, region of interest 2, compositionally biased region 2, chain 1, disulfide bond 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9M0R	ELECTRON MICROSCOPY	2.47
9M2F	ELECTRON MICROSCOPY	2.93
9VI9	ELECTRON MICROSCOPY	3.02
9VIF	ELECTRON MICROSCOPY	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZQ6-F1	78.27	0.57

Antibody-complex structures (SAbDab): 4 — 9M0R, 9M2F, 9VI9, 9VIF

Functional residue map

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

Disulfide bonds (1): 116–203

Glycosylation sites (5): 10, 18, 29, 113, 195

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-389397	Orexin and neuropeptides FF and QRFP bind to their respective receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 57 (showing top): AP1_01, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, TGANTCA_AP1_C, GOBP_RESPONSE_TO_HORMONE, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, KANG_IMMORTALIZED_BY_TERT_DN, GOCC_CILIUM, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOCC_NON_MOTILE_CILIUM

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), cellular response to hormone stimulus (GO:0032870), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), neuropeptide receptor activity (GO:0008188), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding 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	2
G protein-coupled receptor activity	1
signal transduction	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
binding	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPFFR1	NPFF	O15130	995
NPFFR1	NPVF	Q9HCQ7	982
NPFFR1	QRFP	P83859	887
NPFFR1	GAL	P22466	722
NPFFR1	KISS1	Q15726	720
NPFFR1	NPY	P01303	662
NPFFR1	GNRH1	P01148	634
NPFFR1	TAC3	Q9UHF0	626
NPFFR1	PRLH	P81277	600
NPFFR1	GNA15	P30679	559
NPFFR1	FSHB	P01225	534
NPFFR1	GNAQ	P50148	520
NPFFR1	GNRH2	O43555	507
NPFFR1	TACR3	P29371	505
NPFFR1	SUCLG1	P53597	491

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TCP11	NPFFR1	psi-mi:“MI:0915”(physical association)	0.560
NPFFR1	ATP1A3	psi-mi:“MI:0915”(physical association)	0.560
NPFFR1	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
TCP11	NPFFR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): NPFFR1 (Two-hybrid), NPFFR1 (Reconstituted Complex)

ESM2 similar proteins: F1MV99, O08786, O42179, O43613, O43614, O62809, O97661, P0DQD5, P28646, P30551, P30680, P30872, P30873, P30874, P30875, P30935, P30936, P30937, P32238, P32745, P33534, P33535, P34975, P34993, P34994, P35372, P42866, P48146, P49660, P50391, P56718, P56719, P58307, P58308, P79350, Q0GBZ5, Q49LX5, Q49LX6, Q5D0K2, Q5IS39

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

6 interactions.

A	Effect	B	Mechanism
NPFFR1	“up-regulates activity”	GNAI1	binding
NPFFR1	“up-regulates activity”	GNAI3	binding
NPFFR1	“up-regulates activity”	GNAO1	binding
NPFFR1	“up-regulates activity”	GNAZ	binding
“neuropeptide FF receptor agonist”	“up-regulates activity”	NPFFR1	“chemical activation”
NPFF	up-regulates	NPFFR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

909 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70266069:GCAC:G	donor_loss	0.9900
10:70266070:CACT:C	donor_loss	0.9900
10:70266071:ACTC:A	donor_loss	0.9900
10:70266072:CT:C	donor_loss	0.9900
10:70266073:TCA:T	donor_loss	0.9900
10:70266074:CACCA:C	donor_loss	0.9900
10:70266075:A:AC	donor_gain	0.9900
10:70266076:C:CC	donor_gain	0.9900
10:70255010:C:A	donor_gain	0.9800
10:70260209:A:T	acceptor_gain	0.9800
10:70266076:CCA:C	donor_gain	0.9800
10:70255177:T:TA	donor_gain	0.9700
10:70255832:C:CT	acceptor_gain	0.9700
10:70266389:CCC:C	acceptor_gain	0.9700
10:70266390:CCC:C	acceptor_gain	0.9700
10:70266390:CCCT:C	acceptor_loss	0.9700
10:70266392:CTA:C	acceptor_loss	0.9700
10:70266393:T:C	acceptor_loss	0.9700
10:70260220:A:T	acceptor_gain	0.9600
10:70266075:AC:A	donor_gain	0.9600
10:70266076:CC:C	donor_gain	0.9600
10:70266387:CTCCC:C	acceptor_gain	0.9600
10:70266392:C:CC	acceptor_gain	0.9600
10:70255124:C:CT	donor_gain	0.9500
10:70260738:CC:C	acceptor_gain	0.9500
10:70260739:CC:C	acceptor_gain	0.9500
10:70283668:AC:A	donor_gain	0.9500
10:70283669:CC:C	donor_gain	0.9500
10:70259348:AAAG:A	donor_gain	0.9400
10:70266390:CC:C	acceptor_gain	0.9400

AlphaMissense

2791 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70260715:C:G	C116S	0.999
10:70260715:C:T	C116Y	0.999
10:70260716:A:T	C116S	0.999
10:70255629:C:A	W207C	0.998
10:70255629:C:G	W207C	0.998
10:70260714:G:C	C116W	0.998
10:70260735:C:A	W109C	0.998
10:70260735:C:G	W109C	0.998
10:70266147:G:C	N84K	0.998
10:70266147:G:T	N84K	0.998
10:70255642:C:T	C203Y	0.997
10:70260715:C:A	C116F	0.997
10:70260716:A:G	C116R	0.997
10:70260737:A:G	W109R	0.997
10:70260737:A:T	W109R	0.997
10:70255284:G:C	S322R	0.996
10:70255284:G:T	S322R	0.996
10:70255286:T:G	S322R	0.996
10:70255297:G:T	A318D	0.996
10:70255403:A:G	W283R	0.996
10:70255403:A:T	W283R	0.996
10:70255642:C:G	C203S	0.996
10:70255643:A:T	C203S	0.996
10:70266135:A:C	S88R	0.996
10:70266135:A:T	S88R	0.996
10:70266137:T:G	S88R	0.996
10:70255281:G:C	S323R	0.995
10:70255281:G:T	S323R	0.995
10:70255283:T:G	S323R	0.995
10:70255631:A:G	W207R	0.995

dbSNP variants (sampled 300 via entrez): RS1000019110 (10:70277478 T>A), RS1000065365 (10:70280815 A>G,T), RS1000094295 (10:70270637 C>T), RS1000145994 (10:70266633 C>A), RS1000178556 (10:70254739 C>T), RS1000281179 (10:70272544 A>C), RS1000288292 (10:70278285 G>C), RS1000540923 (10:70261677 G>A), RS1000582093 (10:70283751 G>A,T), RS1000833827 (10:70264800 G>A), RS1000943948 (10:70273502 G>A,C), RS1001087359 (10:70267734 T>C,G), RS1001181613 (10:70253738 G>T), RS1001246447 (10:70282341 C>T), RS1001414424 (10:70247534 G>A)

Disease associations

OMIM: gene MIM:607448 | 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
GCST001693_3	Acute lymphoblastic leukemia (childhood)	8.000000e-06
GCST003075_140	Cognitive decline rate in late mild cognitive impairment	3.000000e-07
GCST003075_7	Cognitive decline rate in late mild cognitive impairment	8.000000e-08
GCST004750_32	Squamous cell lung carcinoma	2.000000e-06
GCST010989_85	Body size at age 10	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5951 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 982 (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
CHEMBL376756	KISSPEPTIN-10	3	982

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Neuropeptide FF/neuropeptide AF receptors

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
neuropeptide FF	Full agonist	9.9	pKi
[125I]Y-RFRP-3	Full agonist	9.7	pKd
Y-RFRP-3	Full agonist	9.4	pKi
RFRP-3	Full agonist	9.3	pKi
1DMe	Full agonist	9.0	pKi
[125I]1DMe	Full agonist	8.9	pKd
[3H]NPVF	Full agonist	8.6	pKd
AC262620	Antagonist	8.1	pKi
AC262970	Antagonist	8.1	pKi
BIBP3226	Antagonist	7.8	pKi
EFWSLAAPQRF-NH2	Full agonist	7.3	pKi
RF9	Antagonist	7.2	pKi
compound 46 [PMID: 25268943]	Antagonist	7.09	pKi
MES304	Antagonist	6.95	pKi
compound 8b [PMID: 38522114]	Antagonist	6.68	pKi
compound 16a [PMID: 38522114]	Antagonist	6.64	pKi
pancreatic polypeptide	Partial agonist	5.3	pKi

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4442534	IC50	190 nM
CHEMBL3360829	EC50	4700 nM

ChEMBL bioactivities

249 potent at pChembl≥5 of 252 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL2165920
10.22	Ki	0.06	nM	CHEMBL429731
9.49	Ki	0.32	nM	CHEMBL2208337
9.23	Ki	0.59	nM	CHEMBL2165920
9.14	Ki	0.73	nM	CHEMBL5093771
9.10	Ki	0.8	nM	CHEMBL2208303
9.05	Ki	0.9	nM	CHEMBL2208301
9.00	Ki	1	nM	CHEMBL4793841
8.95	Kd	1.13	nM	CHEMBL429731
8.89	Ki	1.3	nM	CHEMBL2165920
8.77	EC50	1.7	nM	CHEMBL2165920
8.72	IC50	1.9	nM	CHEMBL1672379
8.70	Ki	2	nM	CHEMBL2208325
8.70	Ki	2	nM	CHEMBL2208338
8.70	Ki	2	nM	CHEMBL414263
8.57	Ki	2.7	nM	CHEMBL4797394
8.54	Ki	2.9	nM	CHEMBL4460742
8.44	Ki	3.66	nM	CHEMBL2165920
8.41	Ki	3.85	nM	CHEMBL3360830
8.40	Ki	4	nM	CHEMBL3360830
8.37	Ki	4.3	nM	CHEMBL5090293
8.33	Ki	4.7	nM	CHEMBL5085324
8.33	IC50	4.7	nM	KISSPEPTIN-10
8.31	EC50	4.9	nM	CHEMBL2165920
8.30	Ki	5	nM	CHEMBL2208320
8.22	Ki	6	nM	CHEMBL2208322
8.20	Ki	6.3	nM	CHEMBL5071745
8.18	Ki	6.6	nM	CHEMBL5075638
8.14	Ki	7.2	nM	CHEMBL2208303
8.14	Ki	7.2	nM	CHEMBL5074999
8.12	EC50	7.5	nM	CHEMBL4800237
8.12	EC50	7.586	nM	CHEMBL4800237
8.11	EC50	7.7	nM	CHEMBL2165920
8.10	Ki	7.9	nM	CHEMBL414263
8.00	EC50	9.9	nM	CHEMBL2165920
8.00	Ki	10	nM	CHEMBL2208319
8.00	Ki	10	nM	CHEMBL5082175
7.96	Ki	11	nM	CHEMBL2208340
7.95	Ki	11.2	nM	CHEMBL5091013
7.92	Ki	12	nM	CHEMBL332347
7.92	Ki	12	nM	CHEMBL2440929
7.89	Ki	13	nM	CHEMBL4777535
7.85	Ki	14	nM	CHEMBL1672380
7.82	Ki	15	nM	CHEMBL2208299
7.80	EC50	16	nM	CHEMBL2165920
7.80	Ki	16	nM	CHEMBL5088703
7.80	Kd	15.85	nM	CHEMBL5085324
7.76	EC50	17.5	nM	CHEMBL4793250
7.76	EC50	17.38	nM	CHEMBL4793250
7.75	Ki	18	nM	CHEMBL332347

PubChem BioAssay actives

249 with measured affinity, of 589 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	<0.0001	uM
(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0001	uM
N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-phenylbenzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0003	uM
(2R)-N-[(2S)-1-amino-3-(2-bromophenyl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0007	uM
(2R)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-[[(E)-3-phenylprop-2-enoyl]amino]pentanamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0008	uM
(2S)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-(3-phenothiazin-10-ylpropanoylamino)pentanamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0009	uM
5-(3,4-dichlorophenyl)-1,4-dihydropyrimidin-2-amine	1740888: Displacement of [3H]-FFRF-NH2 from human NPFFR1 expressed in CHO cell membrane by Topcount scintillation counting method	ki	0.0010	uM
(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoic acid	570383: Displacement of (D-[125I]Tyr1, MePhe3)-NPFF from NPFFR1 after 2 hrs	ic50	0.0019	uM
(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]-methylamino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1740824: Displacement of [125I]YVP from human NPFFR1 expressed in HEK293 cells by radioligand binding assay	ki	0.0020	uM
N-[(2R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-phenylbenzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0020	uM
N-[(2R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-phenylbenzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0020	uM
(2S)-2-[3-[(4S)-4-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-oxo-4,5-dihydro-1H-2-benzazepin-2-yl]propanoylamino]-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)pentanamide	2075420: Displacement of [125I]-1-DMe-NPFF from human NPFF1 receptor	ki	0.0027	uM
(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2R)-2,4-diamino-4-oxobutanoyl]pyrrolidine-2-carbonyl]-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1740825: Displacement of [125I]YVP from human NPFFR1 expressed in CHO cells by gamma-counter method	ki	0.0029	uM
(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]-methylamino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1167040: Displacement of [3H]NPVF from human NPFF1 receptor expressed in CHO cells after 1 hr by liquid scintillation counting analysis	ki	0.0039	uM
(2R)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0043	uM
(2S)-2-[[(2R)-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanoyl]amino]-4-methylpentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0047	uM
(2S)-N-[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]butanediamide	570383: Displacement of (D-[125I]Tyr1, MePhe3)-NPFF from NPFFR1 after 2 hrs	ic50	0.0047	uM
N-[(2R)-1-[[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-phenylbenzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0050	uM
N-[(2R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-3-phenylbenzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0060	uM
(2R)-N-[(2R)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0063	uM
(2R)-N-[(2S)-1-amino-1-oxo-4-phenylbutan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0066	uM
(2R)-N-[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0072	uM
(2S)-2-[[(2S)-1-[(4R,7S,13S)-13-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-7-benzyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carbonyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1701331: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay	ec50	0.0075	uM
(2R)-N-[(2R)-1-amino-3-(2-bromophenyl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0100	uM
(2R)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]pentanamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0100	uM
N-[(2R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]benzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0110	uM
(2R)-N-(2-amino-2-oxoethyl)-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0112	uM
(2R)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide	1266467: Binding affinity to human NPFF1 receptor expressed in CHO cells	ki	0.0120	uM
(2S)-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]-N-[(4-hydroxyphenyl)methyl]pentanamide	1740832: Displacement of [125I]YVP from human NPFFR1 expressed in CHO cells	ki	0.0120	uM
2-(4-methylquinolin-2-yl)guanidine	1740860: Binding affinity to human NPFFR1 by radioligand binding assay	ki	0.0130	uM
N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]adamantane-1-carboxamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0140	uM
(2R)-N-[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]pentanamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0150	uM
(2R)-N-[(2R)-1-amino-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0160	uM
(2S)-2-[[(2S)-1-[(2R)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-sulfanylpropanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1701331: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay	ec50	0.0174	uM
(2R)-N-[(1R)-2-amino-2-oxo-1-phenylethyl]-5-(diaminomethylideneamino)-2-[(2,2-diphenylacetyl)amino]pentanamide	1740834: Antagonist activity at human NPFFR1 expressed in CHO-K1 cells assessed as reversal of agonist-induced inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by LANCE ultra cAMP assay	ic50	0.0210	uM
(2R)-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0210	uM
N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]benzamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0230	uM
2-(6-chloro-4-methylquinolin-2-yl)guanidine	1740860: Binding affinity to human NPFFR1 by radioligand binding assay	ki	0.0240	uM
(2S)-2-[[(2S)-1-[(2R)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-sulfanylpropanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1701331: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay	ec50	0.0249	uM
(2S)-2-[[(2S)-1-[(5S,8S,16S)-16-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-benzyl-4-methyl-3,6,10,17-tetraoxo-1,4,7,11-tetrazacycloheptadecane-8-carbonyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1812980: Agonist activity at NPFF1R (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competitive PKA binding assay	ec50	0.0288	uM
N-[(2R)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]adamantane-1-carboxamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0290	uM
(2R)-N-[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0320	uM
(2S)-2-[[(2S)-1-[(4R,7S,13R)-13-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-7-benzyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carbonyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1701331: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay	ec50	0.0324	uM
(2R)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-5-(diaminomethylideneamino)-2-[(2-phenylacetyl)amino]pentanamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0350	uM
(2S,3S)-2-[[(2R)-5-(diaminomethylideneamino)-2-(3,3-diphenylprop-2-enoylamino)pentanoyl]amino]-3-methylpentanamide	1820160: Displacement of [125I]-1DMeNPFF from recombinant human NPFF1 receptor expressed in CHO cells by TopCount scintillation counting method	ki	0.0390	uM
2-[(E)-[5-[2-(trifluoromethyl)phenyl]furan-2-yl]methylideneamino]guanidine	439333: Agonist activity at human NPFF1 receptor expressed in cells assessed as beta-galactosidase levels after 5 days	ec50	0.0398	uM
(2S)-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-[[(2S)-pyrrolidine-2-carbonyl]amino]pentanediamide	1740815: Displacement of [125I]-1DMeNPFF from human NPFFR1 expressed in HEK293 cells incubated for 2 hrs by scintillation counting method	ki	0.0400	uM
2-[(E)-1-adamantylmethylideneamino]guanidine	698092: Competitive antagonist activity at human NPFF1 receptor expressed in COS1 cells assessed as inhibition of NPVF-induced [3H]inositol phosphate accumulation after 2 hrs by liquid scintillation counting	kd	0.0417	uM
N-[(2R)-1-[[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]adamantane-1-carboxamide	718799: Displacement of [3H]FFRF-NH2 from human flag-tagged NPFF1 receptor expressed in CHO cells by scintillation counting	ki	0.0510	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pentanediamide	1714357: Agonist activity at NPFFR1 (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay	ec50	0.0537	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression	1
bisphenol S	decreases methylation	1
Resveratrol	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
S-Nitrosoglutathione	decreases expression	1

ChEMBL screening assays

114 unique, capped per target: 68 functional, 46 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1058558	Functional	Agonist activity at human NPFF1 receptor expressed in cells assessed as beta-galactosidase levels after 5 days	Discovery of selective nonpeptidergic neuropeptide FF2 receptor agonists. — J Med Chem
CHEMBL1681414	Binding	Displacement of (D-[125I]Tyr1, MePhe3)-NPFF from NPFFR1 at 10 uM after 2 hrs	Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands. — ACS Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H475	CHO-K1/NPFF1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV57	cAMP Hunter CHO-K1 NPFFR1 Gi	Spontaneously immortalized cell line	Female
CVCL_KY62	PathHunter CHO-K1 NPFFR1 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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