NTSR1

Summary

NTSR1 (neurotensin receptor 1, HGNC:8039) is a protein-coding gene on chromosome 20q13.33, encoding Neurotensin receptor type 1 (P30989). G-protein coupled receptor for the tridecapeptide neurotensin (NTS).

Neurotensin receptor 1 belongs to the large superfamily of G-protein coupled receptors. NTSR1 mediates the multiple functions of neurotensin, such as hypotension, hyperglycemia, hypothermia, antinociception, and regulation of intestinal motility and secretion.

Source: NCBI Gene 4923 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 101 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002531

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8039
Approved symbol	NTSR1
Name	neurotensin receptor 1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	NTR
Ensembl gene	ENSG00000101188
Ensembl biotype	protein_coding
OMIM	162651
Entrez	4923

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370501, ENST00000482259

RefSeq mRNA: 1 — MANE Select: NM_002531 NM_002531

CCDS: CCDS13502

Canonical transcript exons

ENST00000370501 — 4 exons

Exon	Start	End
ENSE00000663288	62754685	62754886
ENSE00001452871	62708836	62709921
ENSE00003492391	62760018	62762771
ENSE00003534963	62758266	62758356

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 83.65.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8378 / max 46.8066, expressed in 280 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185749	0.3899	164
185748	0.2332	124
209206	0.0831	39
209205	0.0663	34
185750	0.0653	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
muscle layer of sigmoid colon	UBERON:0035805	83.65	gold quality
cortical plate	UBERON:0005343	81.58	gold quality
sigmoid colon	UBERON:0001159	75.71	gold quality
granulocyte	CL:0000094	65.81	gold quality
colon	UBERON:0001155	65.32	gold quality
secondary oocyte	CL:0000655	64.86	gold quality
large intestine	UBERON:0000059	64.66	gold quality
substantia nigra	UBERON:0002038	63.63	gold quality
prefrontal cortex	UBERON:0000451	62.69	gold quality
monocyte	CL:0000576	61.69	gold quality
hair follicle	UBERON:0002073	61.62	gold quality
mononuclear cell	CL:0000842	61.58	gold quality
leukocyte	CL:0000738	61.49	gold quality
midbrain	UBERON:0001891	61.40	gold quality
transverse colon	UBERON:0001157	61.13	gold quality
blood	UBERON:0000178	60.97	gold quality
ganglionic eminence	UBERON:0004023	60.69	gold quality
colonic epithelium	UBERON:0000397	60.59	silver quality
intestine	UBERON:0000160	60.39	gold quality
cingulate cortex	UBERON:0003027	59.59	gold quality
Brodmann (1909) area 10	UBERON:0013541	59.49	gold quality
anterior cingulate cortex	UBERON:0009835	59.35	gold quality
bone marrow	UBERON:0002371	59.26	gold quality
neocortex	UBERON:0001950	58.32	gold quality
frontal cortex	UBERON:0001870	58.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	57.76	gold quality
bone marrow cell	CL:0002092	57.58	gold quality
right frontal lobe	UBERON:0002810	57.07	gold quality
amniotic fluid	UBERON:0000173	56.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	56.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-36552	no	10.23
E-ANND-3	no	1.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, SP1, TCF3, TCF4, TCF7L2

miRNA regulators (miRDB)

80 targeting NTSR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 40)

• Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor (PMID:11559354)
• investigation of its binding to neurotensin (PMID:11906607)
• Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line. (PMID:12360476)
• constant activation of NT1 receptor generates an oncogenic regulation (PMID:14699144)
• neuropeptide neurotensin (NT) binds to freshly isolated Sezary malignant cells and induces through NT1 receptors the cell migration of the cutaneous T cell lymphoma cell line Cou-L. (PMID:14962098)
• NT and NTR1 are part of network activated after mucosal injuries, and NT stimulates epithelial restitution, at least in part, through a COX-2 dependent pathway. (PMID:15764810)
• Ca2+ mobilization elicited by R-NT is via NTR1 (PMID:16087676)
• this report establishs a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation (PMID:16299383)
• NMU & its cancer-specific receptors NTSR1 & GHSR1b, as well as its target genes, are overexpressed in lung cancer and in cell lines, and that those gene products play indispensable roles in the growth and progression of lung cancer cells. (PMID:17018595)
• Binding of NTSR1 in a prostatic neoplasm cell line is sensitive to metabolic stress. (PMID:17289170)
• results suggest that increased NTSR1 expression may be an early event during colonic tumorigenesis and also contribute to tumor progression and aggressive behavior in colonic adenocarcinomas. (PMID:18541341)
• NTR1 and NTR2 mRNA were not detected in either pituitary adenomas or normal tissue. (PMID:18624930)
• Investigating prototypical interactions between NT(8-13) and the human neurotensin receptor 1 (hNTR1), we created a receptor-ligand model that was validated by site-directed mutagenesis and structure-activity relationship studies (PMID:18809332)
• neurotensin receptor-1 pathway contributes to human ductal breast cancer progression (PMID:19156213)
• Our findings suggest that NT produced by type I cells acts in an autocrine or paracrine way on the same cell type, playing a modulatory role on chemoception. (PMID:19864207)
• this study proposes a novel function of NTR2 in the regulation of NTR1 activity. (PMID:19968961)
• Four splice variants of the NTS1 receptor were detected in prostate cancer cell lines. These isoforms are expressed in the prostate cancer cell lines PC3 and DU145, but not in LNCaP or in normal prostate tissue, which only express the normal transcript. (PMID:20018219)
• NTR1 was upregulated in cells with a basal phenotype (cytokeratin 1/5/10/14+) (PMID:20048080)
• Data show that neurotensin- and NTSR1-positive mmunohistochemistry staining in 60.4% and 59.7% of lung adenocarcinomas, respectively. (PMID:20810387)
• Results indicate that the counteraction of neurotensin and neurotensin receptor subtype-1 regulates the genesis and development of pancreatic carcinomas. (PMID:21272935)
• Neurotensin receptor 1 is expressed in gastrointestinal stromal tumors but not in interstitial cells of Cajal. (PMID:21364741)
• NTSR1 single nucleotide polymorphisms were significantly associated with variance in working memory performance among healthy adults. (PMID:21394204)
• Our studies demonstrate that NTSR-1 plamitoylation is required for NTSR-1-mediated MAPK signaling and cellular proliferation in breast cancer cells. (PMID:21725197)
• Integrin alpha(nu) beta(3), NTRS1 and PSCA mRNA expression increased with tumorigenic potential, but mRNA expression levels for these proteins do not translate directly to equivalent expression levels of membrane bound protein. (PMID:21748756)
• Endothelin-converting enzyme-1 (ECE-1) degrades NT in acidic conditions, and its activity is crucial for NTR1 recycling. (PMID:22416137)
• analysis of the role of cholesterol on the activity and stability of neurotensin receptor 1 (PMID:22551944)
• NTSR2 was overexpressed, NTSR1 decreased, and neurotensin was not expressed in B cell leukemia patient’s B-cells, as compared with healthy B cells. (PMID:23109725)
• These results indicate that the association between hippocampal structure and working memory performance was modulated by variation in the NTSR1 gene (PMID:23110888)
• Results show that both the neurotensin (NT) and the neurotensin 1 receptor hNTS1(321-344)fragment present a 3D structure in complex. (PMID:23140271)
• The study found no evidence for the possible association between three NTR1 SNPs and both trait and state anxiety. (PMID:23292156)
• rs6090453C/G polymorphism and the CGG haplotype may enhance schizophrenia susceptibility in the Han Chinese population, while the GCG haplotype may be a protective factor, particularly in females. (PMID:23483448)
• Data indicate that dopamine D2 receptor (D2R) and neurotensin 1 receptor (NTS1R) were colocated in the plasma membrane of cells. (PMID:23624386)
• NTSR1 gene variants are associated with alcohol dependence in a male Han Chinese population. (PMID:23743782)
• The association between NTR1 gene single nucleotide polymorphisms (SNPs) (rs6090453, rs6011914, and rs2427422) and coping styles, were evaluated. (PMID:23807075)
• NTSR1 in colonic epithelial cells is overexpressed in inflammatory bowel disease, in a stepwise fashion with sequential progress from inflammation to dysplasia and carcinoma. (PMID:23901225)
• NTSR1 is commonly high expressed in melanoma cells. (PMID:24357116)
• variations in the NTR1 gene were involved in the biological mechanisms of HA and RD personality traits; however, the effect is influenced by gender. (PMID:24401289)
• Taken together, our results provided a novel regulatory mechanism for GPR39-1b in NTRS1 signaling. (PMID:24512471)
• The current study investigated whether genetic polymorphisms in the NTR1 gene (rs6090453C/G, rs6011914C/G, and rs2427422A/G) were associated with the performance on verbal and visual learning. (PMID:24770449)
• Neurotensin receptor 1 SNPs were significantly associated with processing speed in a sample of Chinese college students. (PMID:25159184)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntsr1	ENSDARG00000077577
mus_musculus	Ntsr1	ENSMUSG00000027568
rattus_norvegicus	Ntsr1	ENSRNOG00000028708

Paralogs (15): BRS3 (ENSG00000102239), MLNR (ENSG00000102539), GHSR (ENSG00000121853), GRPR (ENSG00000126010), NMUR2 (ENSG00000132911), NMBR (ENSG00000135577), EDNRB (ENSG00000136160), EDNRA (ENSG00000151617), NTSR2 (ENSG00000169006), GPR37L1 (ENSG00000170075), GPR37 (ENSG00000170775), NMUR1 (ENSG00000171596), GPR148 (ENSG00000173302), TRHR (ENSG00000174417), GPR39 (ENSG00000183840)

Protein

Protein identifiers

Neurotensin receptor type 1 — P30989 (reviewed: P30989)

Alternative names: High-affinity levocabastine-insensitive neurotensin receptor, NTRH

All UniProt accessions (1): P30989

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for the tridecapeptide neurotensin (NTS). Signaling is effected via G proteins that activate a phosphatidylinositol-calcium second messenger system. Signaling leads to the activation of downstream MAP kinases and protects cells against apoptosis.

Subunit / interactions. Interacts (palmitoylated form) with GNA11.

Subcellular location. Cell membrane. Membrane raft.

Tissue specificity. Expressed in prostate (at protein level). Detected in colon and peripheral blood mononuclear cells. Detected at very low levels in brain.

Post-translational modifications. N-glycosylated. Palmitoylated; this is required for normal localization at membrane rafts and normal GNA11-mediated activation of down-stream signaling cascades. The palmitoylation level increases in response to neurotensin treatment.

Domain organisation. The ligand binding pocket consists mainly of extracellular loops ECL2 and ECL3, as well as transmembrane regions TM6 and TM7.

Similarity. Belongs to the G-protein coupled receptor 1 family. Neurotensin receptor subfamily. NTSR1 sub-subfamily.

RefSeq proteins (1): NP_002522* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR003984	NT_rcpt	Family
IPR003985	NT1_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (48 total): helix 13, topological domain 8, transmembrane region 7, glycosylation site 3, sequence variant 3, turn 3, strand 3, lipid moiety-binding region 2, mutagenesis site 2, chain 1, region of interest 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

48 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9P7Z	ELECTRON MICROSCOPY	2.1
9VAW	ELECTRON MICROSCOPY	2.24
9P80	ELECTRON MICROSCOPY	2.3
7UL2	ELECTRON MICROSCOPY	2.4
20ZG	ELECTRON MICROSCOPY	2.4
20ZH	ELECTRON MICROSCOPY	2.4
9P82	ELECTRON MICROSCOPY	2.4
20ZC	ELECTRON MICROSCOPY	2.6
9P81	ELECTRON MICROSCOPY	2.6
8ZYT	ELECTRON MICROSCOPY	2.65
8ZYU	ELECTRON MICROSCOPY	2.65
20ZI	ELECTRON MICROSCOPY	2.7
20ZK	ELECTRON MICROSCOPY	2.7
9P84	ELECTRON MICROSCOPY	2.7
20ZD	ELECTRON MICROSCOPY	2.8
9P87	ELECTRON MICROSCOPY	2.8
8ZYY	ELECTRON MICROSCOPY	2.83
9VB4	ELECTRON MICROSCOPY	2.85
20ZJ	ELECTRON MICROSCOPY	2.9
9P86	ELECTRON MICROSCOPY	2.9
9P88	ELECTRON MICROSCOPY	2.9
9VAU	ELECTRON MICROSCOPY	2.95
9VAV	ELECTRON MICROSCOPY	2.99
6OS9	ELECTRON MICROSCOPY	3
6OSA	ELECTRON MICROSCOPY	3
9P85	ELECTRON MICROSCOPY	3
9VB7	ELECTRON MICROSCOPY	3.01
8JPF	ELECTRON MICROSCOPY	3.02
9VB3	ELECTRON MICROSCOPY	3.02
8JPB	ELECTRON MICROSCOPY	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30989-F1	80.27	0.55

Antibody-complex structures (SAbDab): 4 — 6OS9, 6PWC, 7UL2, 8ZYU

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): 381, 383

Disulfide bonds (1): 141–224

Glycosylation sites (3): 4, 37, 41

Mutagenesis-validated functional residues (2):

Position	Phenotype
381	abolishes palmitoylation; when associated with s-383.
383	abolishes palmitoylation; when associated with s-381.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 319 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_GLUTAMATE_SECRETION, GOBP_POSITIVE_REGULATION_OF_SEQUESTERING_OF_CALCIUM_ION, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_ACID_SECRETION, GOBP_REGULATION_OF_ICOSANOID_SECRETION, GOBP_COGNITION, MODULE_274, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (34): temperature homeostasis (GO:0001659), negative regulation of systemic arterial blood pressure (GO:0003085), regulation of membrane depolarization (GO:0003254), cAMP biosynthetic process (GO:0006171), response to stress (GO:0006950), G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), adult locomotory behavior (GO:0008344), positive regulation of gene expression (GO:0010628), positive regulation of glutamate secretion (GO:0014049), positive regulation of gamma-aminobutyric acid secretion (GO:0014054), response to food (GO:0032094), regulation of inositol trisphosphate biosynthetic process (GO:0032960), response to lipid (GO:0033993), positive regulation of locomotion (GO:0040017), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), regulation of respiratory gaseous exchange (GO:0043576), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), negative regulation of release of sequestered calcium ion into cytosol (GO:0051280), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), positive regulation of inositol phosphate biosynthetic process (GO:0060732), D-aspartate import across plasma membrane (GO:0070779), inositol phosphate catabolic process (GO:0071545), vocalization behavior (GO:0071625), positive regulation of arachidonate secretion (GO:0090238), positive regulation of inhibitory postsynaptic potential (GO:0097151), L-glutamate import across plasma membrane (GO:0098712), conditioned place preference (GO:1990708), regulation of behavioral fear response (GO:2000822), signal transduction (GO:0007165), learning (GO:0007612), associative learning (GO:0008306)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), G protein-coupled neurotensin receptor activity (GO:0016492), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (17): endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), cell surface (GO:0009986), symmetric synapse (GO:0032280), terminal bouton (GO:0043195), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), perikaryon (GO:0043204), membrane raft (GO:0045121), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), neuronal cell body (GO:0043025), axon terminus (GO:0043679), neuron spine (GO:0044309)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
neuron projection	3
G protein-coupled receptor signaling pathway	2
positive regulation of organic acid transport	2
positive regulation of amino acid transport	2
response to chemical	2
apoptotic process	2
regulation of apoptotic process	2
binding	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
presynapse	2
dendrite	2
multicellular organismal-level homeostasis	1
regulation of systemic arterial blood pressure	1
negative regulation of blood pressure	1
regulation of membrane potential	1
regulation of cellular process	1
membrane depolarization	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cAMP metabolic process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
anterograde trans-synaptic signaling	1
locomotory behavior	1
adult behavior	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
glutamate secretion	1
regulation of glutamate secretion	1
positive regulation of secretion by cell	1
gamma-aminobutyric acid secretion	1
regulation of gamma-aminobutyric acid secretion	1
positive regulation of secretion	1
response to nutrient levels	1
regulation of inositol phosphate biosynthetic process	1

Protein interactions and networks

STRING

1176 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTSR1	NTS	P30990	999
NTSR1	ARRB1	P49407	968
NTSR1	WFIKKN1	Q96NZ8	875
NTSR1	ARRB2	P32121	863
NTSR1	WFIKKN2	Q8TEU8	850
NTSR1	DHX15	O43143	777
NTSR1	PCOLCE	Q15113	771
NTSR1	BDNF	P23560	769
NTSR1	PCOLCE2	Q9UKZ9	759
NTSR1	NGF	P01138	752
NTSR1	NTRK1	P04629	733
NTSR1	SORT1	Q99523	724
NTSR1	NTRK2	Q16620	714
NTSR1	NTF4	P34130	708
NTSR1	COPA	P53621	704

IntAct

51 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
DRD2	DRD2	psi-mi:“MI:2364”(proximity)	0.770
NTSR1	NTS	psi-mi:“MI:0407”(direct interaction)	0.560
NTSR1	NTSR1	psi-mi:“MI:0407”(direct interaction)	0.560
RAMP3	NTSR1	psi-mi:“MI:0915”(physical association)	0.560
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
SCAMP2	SCAMP3	psi-mi:“MI:0914”(association)	0.530
NTSR1	NTS	psi-mi:“MI:0915”(physical association)	0.400
NTS	NTSR1	psi-mi:“MI:0915”(physical association)	0.400
NTSR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	NTSR1	psi-mi:“MI:0915”(physical association)	0.400
DRD2	NTSR1	psi-mi:“MI:0403”(colocalization)	0.380
DRD2	NTSR1	psi-mi:“MI:2364”(proximity)	0.380
NTSR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
ZXDB	SETD1A	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC4E	ESYT2	psi-mi:“MI:0914”(association)	0.350
KLRB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ACKR2	TMEM223	psi-mi:“MI:0914”(association)	0.350
ATP5PF	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ATP5PB	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): NTSR1 (Affinity Capture-RNA), NTS (Reconstituted Complex), TMEM161B (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), NTSR1 (Affinity Capture-MS), ND5 (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), ALG8 (Affinity Capture-MS), HIST1H1C (Affinity Capture-MS), ATP5B (Affinity Capture-MS), PKD2 (Affinity Capture-MS), GPR50 (Affinity Capture-MS), COX1 (Affinity Capture-MS), LACRT (Affinity Capture-MS), SURF4 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R9YJI3, A1ZAX0, B2ZHY2, B4XF06, D4A3U0, O43194, O46635, O55040, O88319, P08911, P08912, P0C0W8, P11617, P14842, P18599, P20789, P28223, P29274, P30543, P30989, P32940, P34979, P35363, P35408, P46616, P50128, P50129, P56490, P70259, Q58CW4, Q5IS53, Q5IS98, Q5R4Q6, Q5U431, Q60613, Q6DWJ6, Q6TLI7, Q75Z89, Q7TQN9, Q8BZ39

Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, O08725, O17239, O42179, O43193, O55040, O88319, O93603, P19020, P20789, P20905, P21917, P24628, P30989, P35367, P49683, P58826, P79291, Q09388, Q25188, Q28553, Q58CW4, Q5QD24, Q63384, Q7JQF1, Q8BZ39, Q8ITC7, Q90WY4, Q923Y8, Q92847, Q93126, Q95254, Q99P50, Q9ESQ4, Q9GZQ4, Q9HB89, Q9JJI5, Q9JJS7

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
NTS	up-regulates	NTSR1	binding
GRK5	“up-regulates activity”	NTSR1	phosphorylation
GRK2	“up-regulates activity”	NTSR1	phosphorylation
NTSR1	“up-regulates activity”	GNAQ	binding
NTSR1	“up-regulates activity”	GNAI1	binding
NTSR1	“up-regulates activity”	GNA13	binding
NTSR1	“up-regulates activity”	GNAO1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	5	11.8×	2e-03
G alpha (s) signalling events	5	9.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	9
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

1304 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62754887:G:GG	donor_gain	1.0000
20:62758394:G:GG	donor_gain	1.0000
20:62760012:CCGCA:C	acceptor_loss	1.0000
20:62760013:CGCA:C	acceptor_loss	1.0000
20:62760014:GCAG:G	acceptor_loss	1.0000
20:62760015:CAG:C	acceptor_loss	1.0000
20:62760016:A:AG	acceptor_gain	1.0000
20:62760016:AGG:A	acceptor_loss	1.0000
20:62760017:G:GA	acceptor_gain	1.0000
20:62760017:GGTT:G	acceptor_gain	1.0000
20:62760017:GGTTC:G	acceptor_gain	1.0000
20:62709921:GGT:G	donor_loss	0.9900
20:62754679:CTGCA:C	acceptor_loss	0.9900
20:62754680:TGCA:T	acceptor_loss	0.9900
20:62754681:GCA:G	acceptor_loss	0.9900
20:62754682:CAGGT:C	acceptor_loss	0.9900
20:62754683:A:AC	acceptor_loss	0.9900
20:62754683:A:AG	acceptor_gain	0.9900
20:62754684:G:GA	acceptor_gain	0.9900
20:62754684:GGTC:G	acceptor_gain	0.9900
20:62754684:GGTCA:G	acceptor_gain	0.9900
20:62758262:TCAG:T	acceptor_loss	0.9900
20:62758263:CA:C	acceptor_loss	0.9900
20:62758265:G:A	acceptor_loss	0.9900
20:62758357:G:GG	donor_gain	0.9900
20:62758375:G:GT	donor_gain	0.9900
20:62760016:AG:A	acceptor_gain	0.9900
20:62760017:GG:G	acceptor_gain	0.9900
20:62760017:GGT:G	acceptor_gain	0.9900
20:62709911:T:TA	donor_gain	0.9800

AlphaMissense

2714 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62709526:A:C	S107R	0.999
20:62709528:C:A	S107R	0.999
20:62709528:C:G	S107R	0.999
20:62709694:A:C	S163R	0.999
20:62709696:T:A	S163R	0.999
20:62709696:T:G	S163R	0.999
20:62709688:A:C	S161R	0.998
20:62709690:C:A	S161R	0.998
20:62709690:C:G	S161R	0.998
20:62760076:A:C	S356R	0.997
20:62760078:C:A	S356R	0.997
20:62760078:C:G	S356R	0.997
20:62709609:G:C	W134C	0.995
20:62709609:G:T	W134C	0.995
20:62709628:T:A	C141S	0.995
20:62709629:G:C	C141S	0.995
20:62709784:T:A	W193R	0.995
20:62709784:T:C	W193R	0.995
20:62709450:C:A	N81K	0.994
20:62709450:C:G	N81K	0.994
20:62709436:G:C	G77R	0.993
20:62709445:G:C	G80R	0.993
20:62709446:G:A	G80D	0.993
20:62758302:C:G	P318R	0.993
20:62758351:G:C	W334C	0.993
20:62758351:G:T	W334C	0.993
20:62760092:C:G	P361R	0.993
20:62758292:T:C	C315R	0.992
20:62760092:C:A	P361H	0.992
20:62709437:G:A	G77D	0.991

dbSNP variants (sampled 300 via entrez): RS1000026060 (20:62711985 A>G), RS1000038499 (20:62754528 C>G,T), RS1000115134 (20:62715175 C>T), RS1000202535 (20:62741109 G>A), RS1000220236 (20:62709871 C>A,G), RS1000343849 (20:62746751 G>T), RS1000376086 (20:62733448 G>T), RS1000392040 (20:62738934 G>C), RS1000482719 (20:62749479 T>C), RS1000626950 (20:62718397 C>A,T), RS1000809370 (20:62740236 A>C), RS1000809590 (20:62713264 A>G), RS1000836706 (20:62735389 C>A,T), RS1000875427 (20:62712031 G>A), RS1000881170 (20:62709205 A>G)

Disease associations

OMIM: gene MIM:162651 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): epilepsy (MONDO:0005027)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007538_6	Cellular nuclear factor (erythroid-derived 2)-like 2 levels	3.000000e-07
GCST009391_280	Metabolite levels	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009794	NRF2 measurement
EFO:0010495	guanosine monophosphate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111438 (PROTEIN FAMILY), CHEMBL3038478 (PROTEIN COMPLEX), CHEMBL4123 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 321,300 (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
CHEMBL113	CAFFEINE	4	200,591
CHEMBL1200485	SORAFENIB TOSYLATE	4	30,403
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL559	DEXTROTHYROXINE	4	3,634
CHEMBL698	TETRACAINE	4	43,379
CHEMBL506981	REMINERTANT	3	235
CHEMBL508338	THIMEROSAL	3
CHEMBL523	NORDAZEPAM	2	4,431

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Neurotensin receptors

Most potent curated ligand interactions (21 total), top 21:

Ligand	Action	Affinity	Parameter
JMV449	Full agonist	10.0	pKi
[125I]neurotensin (human, mouse, rat)	Full agonist	9.9	pKd
EISAI-2	Full agonist	9.8	pKi
neurotensin	Full agonist	9.7	pKi
EISAI-1	Full agonist	9.5	pKi
SR142948A	Antagonist	8.9	pIC50
JMV458	Full agonist	8.8	pKi
large neurotensin	Full agonist	8.7	pIC50
neuromedin N	Full agonist	8.7	pKi
[3H]meclinertant	Antagonist	8.5	pKd
meclinertant	Antagonist	8.4	pKi
ABS-201	Full agonist	8.0	pIC50
KH28	Full agonist	7.92	pIC50
ABS-212	Full agonist	7.64	pIC50
Thr10contulakin-G	Full agonist	7.6	pIC50
SR48527	Antagonist	7.5	pKi
large neuromedin N	Full agonist	7.4	pIC50
contulakin-G	Full agonist	6.0	pIC50
JMV457	Full agonist	5.8	pKi
JMV2004	Full agonist	5.7	pKi
JMV431	Full agonist	5.3	pKi

Binding affinities (BindingDB)

269 measured of 382 human assays (424 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20240287046, Compound I-4	IC50	0.06 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound II-3	IC50	0.06 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-3	IC50	0.062 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound II-2	IC50	0.11 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-9	IC50	0.132 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-7	IC50	0.206 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-5	IC50	0.22 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
CHEMBL2431105	IC50	0.24 nM
US20240287046, Compound II-1	IC50	0.298 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-11	IC50	0.323 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
Ref: WO9632382 A1 1996-10-17	IC50	0.39 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-1	IC50	0.39 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-2	IC50	0.421 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-8	IC50	0.451 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
CHEMBL3086356	KI	0.98 nM
US20240287046, Compound I-10	IC50	1.14 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-13	IC50	2.2 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
H-Arg-Arg-Pro-Tyr-Ile-Aac-OH	KI	2.4 nM
US20240287046, Compound I-12	IC50	2.89 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-14	IC50	2.96 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
US20240287046, Compound I-6	IC50	10.5 nM	US-20240287046: COMPOUNDS AND RADIOLIGANDS FOR TARGETING NEUROTENSIN RECEPTOR AND USES THEREOF
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
3-(4-fluorophenyl)-7,8-dimethoxy-5-[(4-methoxyphenyl)methyl]pyrazolo[4,3-c]quinoline	EC50	1150 nM
4-[4-[2-(azetidin-1-yl)phenyl]piperazin-1-yl]-2-cyclopropyl-N,N-dimethylquinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
4-[4-[2-(azetidin-1-yl)phenyl]piperazin-1-yl]-2-cyclopropyl-N-ethyl-N-methylquinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[4-[4-[2-(azetidin-1-yl)phenyl]piperidin-1-yl]-2-cyclopropylquinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
4-[4-[2-(azetidin-1-yl)phenyl]piperidin-1-yl]-2-cyclopropyl-N-methyl-N-(2-morpholin-4-ylethyl)quinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-(1-fluorocyclopropyl)-N-(2-methoxyethyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]-N-methylquinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]-N-methyl-N-(2-morpholin-4-ylethyl)quinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]-N,N-dimethylquinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]-N-methyl-N-propylquinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[2-cyclobutyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[4-[4-[2-(dimethylamino)phenyl]piperidin-1-yl]-2-[1-(trifluoromethyl)cyclopropyl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[4-[4-[2-(dimethylamino)phenyl]piperidin-1-yl]-2-[1-(trifluoromethyl)cyclopentyl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
4-[4-[2-(dimethylamino)phenyl]piperidin-1-yl]-2-(1-fluorocyclobutyl)-N-methyl-N-(2-morpholin-4-ylethyl)quinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[4-[4-(2-methoxyphenyl)piperidin-1-yl]-2-[1-(trifluoromethyl)cyclobutyl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[4-[4-[2-(dimethylamino)phenyl]piperidin-1-yl]-2-(1-methylcyclobutyl)quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
4-[4-(2-methoxyphenyl)piperidin-1-yl]-N-methyl-2-(1-methylcyclobutyl)-N-(2-morpholin-4-ylethyl)quinazolin-6-amine	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[4-[4-(2-methoxyphenyl)piperidin-1-yl]-2-(1-methylcyclobutyl)quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[2-(1-fluorocyclopentyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
1-[2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]pyrrolidin-3-ol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]-6-(3-methoxypyrrolidin-1-yl)quinazoline	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
(R)-1-{2-cyclopropyl-4-[4-(2- methoxy-phenyl)-piperidin-1-yl]- quinazolin-6-yl}-pyrrolidin-3-ol, HCl salt	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
(3S)-1-[2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]pyrrolidin-3-ol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]-6-[(3R)-3-methoxypyrrolidin-1-yl]quinazoline	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]-6-[(3S)-3-methoxypyrrolidin-1-yl]quinazoline	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[2-(dimethylamino)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[7-chloro-2-cyclopropyl-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[2-cyclopropyl-4-[4-(4-fluoro-2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1
2-[[2-cyclopropyl-4-[4-(5-fluoro-2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino]ethanol	EC50	1250 nM	US-10118902: Small molecule agonists of neurotensin receptor 1

ChEMBL bioactivities

909 potent at pChembl≥5 of 1082 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL3622802
10.38	EC50	0.0416	nM	CHEMBL415788
10.16	EC50	0.06918	nM	CHEMBL415788
10.10	IC50	0.08	nM	CHEMBL258221
9.89	Ki	0.1288	nM	CHEMBL415788
9.85	Ki	0.14	nM	CHEMBL415788
9.85	IC50	0.14	nM	Demotensin 1
9.85	Ki	0.14	nM	CHEMBL342252
9.82	EC50	0.15	nM	CHEMBL415788
9.80	Kd	0.16	nM	CHEMBL342252
9.80	IC50	0.16	nM	NEUROTENSIN
9.74	IC50	0.18	nM	DEMOTENSIN 2
9.72	Ki	0.19	nM	CHEMBL415788
9.70	IC50	0.2	nM	NEUROTENSIN
9.65	Ki	0.223	nM	CHEMBL4593174
9.64	EC50	0.23	nM	NEUROTENSIN
9.64	Ki	0.23	nM	CHEMBL1766935
9.62	IC50	0.24	nM	NEUROTENSIN
9.62	IC50	0.24	nM	CHEMBL2431105
9.62	Ki	0.24	nM	CHEMBL415788
9.62	EC50	0.24	nM	CHEMBL4789659
9.62	Ki	0.24	nM	CHEMBL1766928
9.62	IC50	0.24	nM	CHEMBL133340
9.60	IC50	0.25	nM	CHEMBL4128926
9.60	IC50	0.25	nM	CHEMBL336836
9.59	Ki	0.26	nM	CHEMBL3786779
9.59	EC50	0.26	nM	CHEMBL4744531
9.57	Ki	0.27	nM	NEUROTENSIN
9.57	Ki	0.27	nM	CHEMBL342252
9.55	Ki	0.28	nM	CHEMBL4526200
9.55	IC50	0.28	nM	CHEMBL133850
9.54	Ki	0.29	nM	CHEMBL342252
9.54	Ki	0.29	nM	CHEMBL4528687
9.54	Ki	0.29	nM	CHEMBL468951
9.54	Ki	0.29	nM	NEUROTENSIN
9.52	IC50	0.3	nM	CHEMBL408381
9.52	IC50	0.3	nM	CHEMBL408127
9.52	IC50	0.3	nM	CHEMBL132524
9.52	IC50	0.3	nM	CHEMBL342252
9.52	IC50	0.3	nM	CHEMBL430910
9.52	IC50	0.3	nM	CHEMBL434227
9.49	IC50	0.32	nM	Demotensin 1
9.48	IC50	0.33	nM	NEUROTENSIN
9.48	IC50	0.33	nM	CHEMBL258221
9.48	Ki	0.33	nM	CHEMBL415788
9.47	EC50	0.34	nM	CHEMBL3622803
9.47	IC50	0.34	nM	CHEMBL337260
9.47	IC50	0.34	nM	CHEMBL129953
9.44	Ki	0.36	nM	CHEMBL3785233
9.44	IC50	0.36	nM	CHEMBL133378

PubChem BioAssay actives

593 with measured affinity, of 1380 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
(2R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-trimethylsilylpropanoic acid	1251023: Displacement of [125I]-Tyr3-NT from human NTS1 receptor expressed in CHOK1 cell membranes incubated for 30 mins by gamma-counting based competitive radioligand binding assay	ic50	<0.0001	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	1182263: Agonist activity at NTSR1 (unknown origin) expressed in CHO cells assessed as potentiation of NT(8-13) peptide-induced change in intracellular Ca2+ level preincubated for 45 mins by FLIPR assay	ec50	<0.0001	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	268354: Displacement of [125I]Tyr3-NT from human NTS1R expressed in WiDr cells	ic50	0.0001	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	1926230: Inhibition of human NTR1	ic50	0.0001	uM
(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	414526: Binding affinity to human NTR1	ki	0.0001	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-(methylamino)pentanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tris(2,2,2-trifluoroacetic acid)	1510626: Displacement of [3H]UR-MK300 from human NSTR1 in HT-29 cells incubated for 2 hrs by liquid scintillation counter	ki	0.0002	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(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]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-methylpentanoic acid	1697048: Agonist activity at human NTS1 expressed in HEK293 cells co-expressing Galphaq/RlucII/GFP10-Ggamma1/Gbeta1 assessed as increase in Galphaq activation incubated for 10 mins in presence of coelenterazine 400A by BRET assay	ec50	0.0002	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-4-carboxy-2-[[(2S)-3-(4-hydroxyphenyl)-2-[[(2S)-4-methyl-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanoyl]amino]propanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0002	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(methylamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0002	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxycyclohexa-1,3-dien-1-yl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	593495: Displacement of [3H]neurotensin from human NTS1 receptor expressed in CHO cells	ki	0.0002	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(3S)-3-amino-6-(diaminomethylideneamino)hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	593495: Displacement of [3H]neurotensin from human NTS1 receptor expressed in CHO cells	ki	0.0002	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[6-amino-2-[[2-[[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propanoyl]amino]acetyl]amino]hexyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	268354: Displacement of [125I]Tyr3-NT from human NTS1R expressed in WiDr cells	ic50	0.0002	uM
2-[[5-(2,6-dimethoxyphenyl)-1-[4-[3-(dimethylamino)propyl-methylcarbamoyl]-2-propan-2-ylphenyl]pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid;hydrochloride	1061657: Displacement of [125I]-neurotensin from NTR1 (unknown origin)	ic50	0.0002	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-3-[4-(aminomethyl)cyclohexyl]-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-2-(1-carbamimidoylpiperidin-4-yl)acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0003	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]-2-piperidin-4-ylacetyl]pyrrolidine-2-carbonyl]amino]-2-(1-carbamimidoylpiperidin-4-yl)acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0003	uM
(2R)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2,6-diaminohexanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-trimethylsilylpropanoyl]amino]-3-trimethylsilylpropanoic acid	1251026: Agonist activity at human NTS1 receptor expressed in CHOK1 cells co-expressing hNTS1-GFP10/RlucII-beta-arrestin 2 assessed as beta-arrestin2 recruitment incubated for 15 mins by BRET assay	ec50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-[[amino-[2-[2-(2-aminoethoxy)ethoxy]ethylcarbamoylamino]methylidene]amino]pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tetrakis(2,2,2-trifluoroacetic acid)	1289937: Displacement of [3H]-{Nomega-[N-(4-propanoylaminobutyl)aminocarbonyl]}Arg-Arg-ProTyr-Ile-Leu-OH Tris(hydrotrifluoroacetate) from NTSR1 in human HT-29 cells after 2 hrs by liquid scintillation counting	ki	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-4-carboxy-2-[[(2S)-3-(4-hydroxyphenyl)-2-[[(2S)-4-methyl-2-[(5-oxopyrrolidine-2-carbonyl)amino]pentanoyl]amino]propanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	1510635: Antagonist activity at NSTR1 (unknown origin) assessed as inhibitory constant	ki	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]-methylamino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tris(2,2,2-trifluoroacetic acid)	1510626: Displacement of [3H]UR-MK300 from human NSTR1 in HT-29 cells incubated for 2 hrs by liquid scintillation counter	ki	0.0003	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-6-amino-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]hexanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-methylpentanoic acid	1697048: Agonist activity at human NTS1 expressed in HEK293 cells co-expressing Galphaq/RlucII/GFP10-Ggamma1/Gbeta1 assessed as increase in Galphaq activation incubated for 10 mins in presence of coelenterazine 400A by BRET assay	ec50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(imidazolidin-2-ylamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-[[amino(ethylamino)methylidene]amino]pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-7-(dimethylamino)heptanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
[(4S)-4-amino-5-[[N’-[(4S)-4-amino-5-[(2S)-2-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-oxopentyl]carbamimidoyl]amino]-5-oxopentyl]-trimethylazanium	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-6-(methylamino)hexanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-[(N’-methylcarbamimidoyl)amino]pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2,6-diaminohexanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0003	uM
(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-(methylamino)pentanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	414520: Displacement of [125I]I-Tyr(3)NT from human NTR1	ki	0.0003	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494758: Displacement of [125I]Tyr3-neurotensin from human recombinant NTS1 receptor after 120 mins by scintillation counting analysis	ic50	0.0003	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0004	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2R)-6-amino-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-2-(1-carbamimidoylpiperidin-4-yl)acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-[[amino-[4-(2,3-ditritiopropanoylamino)butylcarbamoylamino]methylidene]amino]pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tris(2,2,2-trifluoroacetic acid)	1289940: Binding affinity to NTSR1 in human HT-29 cells after 2 hrs by liquid scintillation counting in presence of NTSR2 ligand (S)-2-((2S,3S)-2-(2-((S)-1-((S)-2-((S)-2-amino-5-guanidinopentanamido)-5-guanidinopentanoyl)-N-(4-hydroxyphenethyl)pyrrolidine-2-carboxamido)acetamido)-3-methylpentanamido)-4-methylpentanoic acid	kd	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-[[amino-[2-[2-[2-(propanoylamino)ethoxy]ethoxy]ethylcarbamoylamino]methylidene]amino]pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tris(2,2,2-trifluoroacetic acid)	1289937: Displacement of [3H]-{Nomega-[N-(4-propanoylaminobutyl)aminocarbonyl]}Arg-Arg-ProTyr-Ile-Leu-OH Tris(hydrotrifluoroacetate) from NTSR1 in human HT-29 cells after 2 hrs by liquid scintillation counting	ki	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-5-[[amino-[2-[2-(2-aminoethoxy)ethoxy]ethylcarbamoylamino]methylidene]amino]-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tetrakis(2,2,2-trifluoroacetic acid)	1289937: Displacement of [3H]-{Nomega-[N-(4-propanoylaminobutyl)aminocarbonyl]}Arg-Arg-ProTyr-Ile-Leu-OH Tris(hydrotrifluoroacetate) from NTSR1 in human HT-29 cells after 2 hrs by liquid scintillation counting	ki	0.0004	uM
4-[2-[(1E,3E,5E)-5-[1-[6-[4-[[N’-[(4S)-4-amino-5-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-oxopentyl]carbamimidoyl]carbamoylamino]butylamino]-6-oxohexyl]-3,3-dimethyl-5-sulfoindol-2-ylidene]penta-1,3-dienyl]-3,3-dimethylindol-1-ium-1-yl]butane-1-sulfonate;bis(2,2,2-trifluoroacetic acid)	1541730: Agonist activity at human neurotensin receptor 1 expressed in CHO cells assessed as increase in intracellular calcium by Fluo-4 dye based fluorescence assay	ec50	0.0004	uM
4-[2-[(1E,3E,5E)-5-[1-[6-[2-[2-[2-[[N’-[(4S)-4-amino-5-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-oxopentyl]carbamimidoyl]carbamoylamino]ethoxy]ethoxy]ethylamino]-6-oxohexyl]-3,3-dimethyl-5-sulfoindol-2-ylidene]penta-1,3-dienyl]-3,3-dimethylindol-1-ium-1-yl]butane-1-sulfonate;bis(2,2,2-trifluoroacetic acid)	1541730: Agonist activity at human neurotensin receptor 1 expressed in CHO cells assessed as increase in intracellular calcium by Fluo-4 dye based fluorescence assay	ec50	0.0004	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-carboxybutanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-2-(1-carbamimidoylpiperidin-4-yl)acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3,3-dimethylbutanoyl]amino]-4,4-dimethylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2,7-diaminoheptanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-6-(dimethylamino)hexanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0004	uM
(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(dimethylamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0004	uM
2-[[5-(2,6-dimethoxyphenyl)-1-[4-[3-(dimethylamino)propyl-methylcarbamoyl]-2-propan-2-ylphenyl]pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid	1802507: SPR Screening Assay from Article 10.1021/acschembio.6b00646: “Ligand Discovery for a Peptide-Binding GPCR by Structure-Based Screening of Fragment- and Lead-Like Chemical Libraries.”	kd	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-1-[(2R)-6-amino-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-2-[4-(diaminomethylideneamino)phenyl]acetyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0004	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]-methylamino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	388349: Displacement of [3H]NT(8-13) from wild type human NTR1 expressed in HEK293 cells	ki	0.0005	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2R)-6-amino-2-[[2-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-[4-(diaminomethylideneamino)phenyl]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147045: Binding affinity towards neurotensin receptor in membranes prepared from HT-29 cell line, relative to [111In]-labeled neurotensin peptide	ic50	0.0005	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-[[amino-[4-(2,3-ditritiopropanoylamino)butylcarbamoylamino]methylidene]amino]pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	1541732: Binding affinity to human neurotensin receptor 1	ki	0.0005	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-[[amino-(4-aminobutylcarbamoylamino)methylidene]amino]pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tetrakis(2,2,2-trifluoroacetic acid)	1289937: Displacement of [3H]-{Nomega-[N-(4-propanoylaminobutyl)aminocarbonyl]}Arg-Arg-ProTyr-Ile-Leu-OH Tris(hydrotrifluoroacetate) from NTSR1 in human HT-29 cells after 2 hrs by liquid scintillation counting	ki	0.0005	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-[[amino-[4-(propanoylamino)butylcarbamoylamino]methylidene]amino]pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid;tris(2,2,2-trifluoroacetic acid)	1289937: Displacement of [3H]-{Nomega-[N-(4-propanoylaminobutyl)aminocarbonyl]}Arg-Arg-ProTyr-Ile-Leu-OH Tris(hydrotrifluoroacetate) from NTSR1 in human HT-29 cells after 2 hrs by liquid scintillation counting	ki	0.0005	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-7-(methylamino)heptanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147064: Evaluated for binding affinity by inhibiting binding of [125I]-Tyr(3)-NT to human Neurotensin receptor 1	ic50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
tobacco tar	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
neurotensin 69L	affects binding	1
pinostrobin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ormosil	affects binding, increases expression	1
licochalcone B	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Dactinomycin	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Fonofos	increases methylation	1
Fluorouracil	decreases expression, affects response to substance	1
Isoflavones	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	affects methylation	1
Neurotensin	affects binding	1

ChEMBL screening assays

216 unique, capped per target: 173 binding, 38 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4880283	Binding	Neurotensin receptor (h) CEREP ligand profiling	Data for DCP probe ABT-546
CHEMBL857327	Functional	Effect on second messenger (PI or cGMP) turnover at human neurotensin receptor; ND=Not determined	Synthesis of partially non-peptidic neurotensin mimetics — Bioorg Med Chem Lett
CHEMBL3871846	ADMET	Displacement of [3H]neurotensin from human NTS1 receptor expressed in CHOK1 cell membranes after 60 mins by scintillation counting	NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 3 cancer cell line, 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8RQ	Ubigene HCT 116 NTSR1 KO	Cancer cell line	Male
CVCL_H482	CHO-K1/NTS1	Spontaneously immortalized cell line	Female
CVCL_KY66	PathHunter CHO-K1 NTSR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA93	PathHunter U2OS NTSR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_YK55	U2OS NTSR1 HiTSeeker	Cancer cell line	Female
CVCL_ZK62	GeneBLAzer NTSR1-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy