TACR1

Summary

TACR1 (tachykinin receptor 1, HGNC:11526) is a protein-coding gene on chromosome 2p12, encoding Substance-P receptor (P25103). Receptor for the tachykinin substance P, also able to bind and respond to tachynins neurokinin A/substance K and neurokinin B/neuromedin-K.

This gene belongs to a gene family of tachykinin receptors. These tachykinin receptors are characterized by interactions with G proteins and contain seven hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin substance P, also referred to as neurokinin 1. The encoded protein is also involved in the mediation of phosphatidylinositol metabolism of substance P.

Source: NCBI Gene 6869 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dopa-responsive dystonia due to sepiapterin reductase deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 265 total — 21 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 42 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001058

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11526
Approved symbol	TACR1
Name	tachykinin receptor 1
Location	2p12
Locus type	gene with protein product
Status	Approved
Aliases	SPR, NK1R, NKIR
Ensembl gene	ENSG00000115353
Ensembl biotype	protein_coding
OMIM	162323
Entrez	6869

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000305249, ENST00000409848, ENST00000497764

RefSeq mRNA: 2 — MANE Select: NM_001058 NM_001058, NM_015727

CCDS: CCDS1958, CCDS46345

Canonical transcript exons

ENST00000305249 — 5 exons

Exon	Start	End
ENSE00000766571	75051251	75051447
ENSE00000766572	75053605	75053755
ENSE00000766573	75120574	75120768
ENSE00001167527	75198546	75199520
ENSE00001177315	75046463	75049723

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 80.27.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7410 / max 37.0263, expressed in 247 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29269	0.7410	247

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.27	gold quality
endocervix	UBERON:0000458	76.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.17	gold quality
ectocervix	UBERON:0012249	73.48	gold quality
body of uterus	UBERON:0009853	71.83	gold quality
left uterine tube	UBERON:0001303	71.69	gold quality
adipose tissue	UBERON:0001013	70.76	gold quality
connective tissue	UBERON:0002384	70.22	gold quality
tendon of biceps brachii	UBERON:0008188	69.99	silver quality
calcaneal tendon	UBERON:0003701	69.90	gold quality
tendon	UBERON:0000043	69.58	gold quality
omental fat pad	UBERON:0010414	69.39	gold quality
peritoneum	UBERON:0002358	69.31	gold quality
smooth muscle tissue	UBERON:0001135	69.07	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.71	gold quality
vagina	UBERON:0000996	68.47	gold quality
tibial nerve	UBERON:0001323	68.31	gold quality
inferior olivary complex	UBERON:0002127	68.26	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	68.26	gold quality
upper leg skin	UBERON:0004262	68.01	gold quality
putamen	UBERON:0001874	67.72	gold quality
caudate nucleus	UBERON:0001873	67.68	gold quality
mucosa of stomach	UBERON:0001199	67.30	gold quality
skin of abdomen	UBERON:0001416	67.15	gold quality
sural nerve	UBERON:0015488	67.04	gold quality
skin of hip	UBERON:0001554	66.63	gold quality
parietal pleura	UBERON:0002400	66.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	66.38	gold quality
zone of skin	UBERON:0000014	66.10	gold quality
right uterine tube	UBERON:0001302	65.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1, NFKB

miRNA regulators (miRDB)

92 targeting TACR1, 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-4776-3P	100.00	68.73	1340
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3180-5P	99.82	69.12	2422

Literature-anchored findings (GeneRIF, showing 40)

• Demonstration of authentic and functional NK-1 receptors in microglia identifies substance P as a potentially important contributor to CNS inflammatory responses. during disease states. (PMID:11857684)
• Tachykinin NK1 receptor-mediated relaxations are non-neurogenic (i.e., unaffected by tetrodotoxin) in penile tissues and are additive with neurogenogenic relaxations elicited by electric field stimulation. (PMID:11906947)
• Involvement of the second extracellular loop (E2) of the neurokinin-1 receptor in the binding of substance P (PMID:11950831)
• Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro. (PMID:12067742)
• role in human colon circular muscle; alterations in diverticular disease (PMID:12130725)
• Analyses of the 5’ flanking sequence in BM stroma and three neural cell lines indicated that sequence +1/+358 relative to the transcription start (TS) site could account for the differences in NK-1 expression between bone marrow and neurons. (PMID:12147210)
• Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers. The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may involve NK-1 receptors in prefrontal cortex. (PMID:12151774)
• This protein is expressed in the human Caco-2 cell line. (PMID:12383866)
• Cgamma H2 of Met174 side chain is the site of covalent attachment to neurokinin-1 receptor of a substance P analog photoactivable in position 5. (PMID:12393913)
• Substance P is expressed in human articular cartilage and is involved in chondrocyte mechanotransduction via the NK1 receptor in an autocrine and paracrine manner. (PMID:12528114)
• The NK-1 receptor expressed in NT2-N neuronal cells is functionally involved in the regulation of macrophage inflammatory protein 1 beta and may play a major role in modulating neuronal functions related to immune regulatory activities within the CNS. (PMID:12548712)
• NK-1R is regulated by NF-kappa B in human macrophages (PMID:12594338)
• a role for substance P and its receptor, neurokinin NK(1) receptor, in the brainstem nuclei in the development of emesis (review) (PMID:12686752)
• results provide the anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain, but do not suggest a region-specific role of the two isoforms in the CNS (PMID:12752772)
• Data demonstrate the existence of two independent binding components in CHO cells transfected with the human neurokinin-1 (NK-1) receptor. (PMID:12810079)
• Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis (PMID:14601651)
• demonstrate the presence of the tachykinin receptors NK1 and NK3 in platelets and present evidence for the involvement of NK1 in SP-mediated platelet aggregation (PMID:15130944)
• reorganization of the plasma membrane has an effect on the activation of the raft-associated NK1R and the down-stream events such as recruitment of protein kinases (PMID:15590676)
• NK-1 receptor immunoreaction could be detected in inner parts of the walls of large blood vessels and in the walls of small blood vessels of normal and chronic painful Achilles and patellar tendons (PMID:15664664)
• NK-1 deficient cells did not proliferate when they were placed as cocultures with bone marrow stroma, which suggests that NK-1 signaling is important for the survival of NB cells in bone marrow. (PMID:15690122)
• These data suggest substance P-induced vasodilatation delivered via microdialysis contains an NO component but does not contain an H1 receptor activation component at the doses tested. (PMID:16123103)
• These results suggest that bFGF, TGF-beta1, and TNF-alpha in synovial tissue and fluid play a role in the regulation of long neurokinin-1 expression in synovial fibroblasts of rheumatoid arthritis patients. (PMID:16154193)
• present data emphasize the role of NK1r in tachykinin-mediated neuronal processes regulating intestinal motility (PMID:16305827)
• two binding sites are independent and non-interconvertible on the time scale of these experiments (PMID:16618119)
• ERK1/2 is activated by a chimeric neurokinin 1 receptor-beta-arrestin1 fusion protein (PMID:16670094)
• Results demonstrate that there are unique characteristics of neurokinin-1 receptor (NK-1R) expression and NK-1R-mediated signaling between undifferentiated THP-1 cells and THP-1 cells differentiated to the macrophage phenotype. (PMID:16675550)
• this study has demonstrated that the NK(1) receptor is widely distributed in the amygdala, and has shown for the first time a high relative density of NK(1) receptor-immunoreactive cell bodies in the basal nucleus of Meynert. (PMID:16815618)
• Data explored a role for NK1 as a potential target for breast cancer treatment and suggest that similar mechanisms might be operative for other cancers showing preference for bone marrow metastases. (PMID:16901764)
• NK(1) receptors contribute to active vasodilatation, and combined NK(1) receptor desensitization and NO synthase inhibition further diminishes active vasodilatation. (PMID:17023511)
• NK1 receptors modulate CaV2.3 using three different signaling mechanisms: a fast inhibition mediated by Gbeta gamma, a slow inhibition mediated by Galpha(q/11), and a slow stimulation mediated by protein kinases C. (PMID:17050807)
• Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress. (PMID:17370082)
• studied gene variants of Tachykinin Receptor 1 in 167 suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 individuals who committed suicide and 312 healthy subjects (PMID:17443717)
• This study showed that the same isoforms of the neurokinin-1 receptor are present in human retinoblastoma cell lines WERI-Rb-1 and Y-79. Both L-732,138 and L-733,060 can induce apoptosis in these cell lines (PMID:17525212)
• Functional consequences of alteration of N-linked glycosylation sites on NK1R were studied. (PMID:17563389)
• Changes in SP receptor expression during chronic inflammation suggest that SP receptors are potential targets for therapeutic regulation of the inflammatory bowel disease. (PMID:17602742)
• NK1 receptor mRNA and protein expression were enhanced in obstructive sleep apnea. (PMID:17667845)
• Evidence was also obtained that the proper clustering of the receptor in these microdomains was important for effective agonist-induced NK1-R signaling and for its interaction with beta-arrestin2. (PMID:17713785)
• NK1R expressing neurons in different subregions of the ventral respiratory group have diverse roles and provide insight on the modulatory role of substance P. (PMID:18085301)
• substance P receptor mediates ERK1/2 phosphorylation in a calcium-dependent manner (PMID:18095097)
• T-2328 is a potent, centrally active NK(1) antagonist. (PMID:18187929)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tacr1a	ENSDARG00000035533
danio_rerio	tacr1b	ENSDARG00000102900
mus_musculus	Tacr1	ENSMUSG00000030043
rattus_norvegicus	Tacr1	ENSRNOG00000005853
caenorhabditis_elegans		WBGENE00006576

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), PROKR1 (ENSG00000169618), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR88 (ENSG00000181656), GPR19 (ENSG00000183150), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

Substance-P receptor — P25103 (reviewed: P25103)

Alternative names: NK-1 receptor, Tachykinin receptor 1

All UniProt accessions (1): P25103

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the tachykinin substance P, also able to bind and respond to tachynins neurokinin A/substance K and neurokinin B/neuromedin-K. The rank order of affinity of this receptor to tachykinins is: substance P > neurokinin A/substance K > neurokinin B/neuromedin-K. Substance P binding to its receptor triggers G protein-coupled receptor signaling via activation of phosphatidylinositol hydrolysis by phospholipase C. Substance P binding also triggers signaling via activation of adenylate cyclase activity which results in increased intracellular levels of cyclic AMP (cAMP).

Subunit / interactions. Interacts with ARRB1.

Subcellular location. Cell membrane. Early endosome.

Miscellaneous. In contrast to Fong et al. data, isoform 2 is not detected by PCR in any of 24 human tissues examined including the placenta.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P25103-1	1	yes
P25103-3	2

RefSeq proteins (2): NP_001049, NP_056542 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000046	NK1_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR001681	Neurokn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (50 total): helix 11, topological domain 8, strand 8, transmembrane region 7, turn 4, glycosylation site 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, binding site 1, lipid moiety-binding region 1, disulfide bond 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
6HLP	X-RAY DIFFRACTION	2.2
6HLO	X-RAY DIFFRACTION	2.4
8U26	ELECTRON MICROSCOPY	2.5
6J20	X-RAY DIFFRACTION	2.7
7P00	ELECTRON MICROSCOPY	2.71
7P02	ELECTRON MICROSCOPY	2.87
7RMG	ELECTRON MICROSCOPY	3
7RMH	ELECTRON MICROSCOPY	3.1
7RMI	ELECTRON MICROSCOPY	3.2
6J21	X-RAY DIFFRACTION	3.2
6HLL	X-RAY DIFFRACTION	3.27
6E59	X-RAY DIFFRACTION	3.4
2KS9	SOLUTION NMR
2KSA	SOLUTION NMR
2KSB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25103-F1	79.07	0.49

Antibody-complex structures (SAbDab): 6 — 7P00, 7P02, 7RMG, 7RMH, 7RMI, 8U26

Functional residue map

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

Ligand- & substrate-binding residues (1): 197

Post-translational modifications (1): 322

Disulfide bonds (1): 105–180

Glycosylation sites (2): 14, 18

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-380095	Tachykinin receptors bind tachykinins
R-HSA-416476	G alpha (q) signalling events
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 473 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, ATF_B, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_93, GOBP_EXCRETION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS

GO Biological Process (47): aggressive behavior (GO:0002118), positive regulation of leukocyte migration (GO:0002687), angiotensin-mediated drinking behavior (GO:0003051), inflammatory response (GO:0006954), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), phospholipase C-activating tachykinin receptor signaling pathway (GO:0007209), tachykinin receptor signaling pathway (GO:0007217), long-term memory (GO:0007616), associative learning (GO:0008306), detection of abiotic stimulus (GO:0009582), response to ozone (GO:0010193), positive regulation of epithelial cell migration (GO:0010634), response to auditory stimulus (GO:0010996), regulation of smooth muscle cell migration (GO:0014910), positive regulation of synaptic transmission, cholinergic (GO:0032224), positive regulation of synaptic transmission, GABAergic (GO:0032230), response to estradiol (GO:0032355), response to progesterone (GO:0032570), response to nicotine (GO:0035094), operant conditioning (GO:0035106), sperm ejaculation (GO:0042713), eating behavior (GO:0042755), positive regulation of vascular permeability (GO:0043117), response to ethanol (GO:0045471), positive regulation of action potential (GO:0045760), positive regulation of blood pressure (GO:0045777), positive regulation of ossification (GO:0045778), positive regulation of vasoconstriction (GO:0045907), positive regulation of hormone secretion (GO:0046887), behavioral response to pain (GO:0048266), regulation of smooth muscle cell proliferation (GO:0048660), positive regulation of lymphocyte proliferation (GO:0050671), positive regulation of epithelial cell proliferation (GO:0050679), positive regulation of stress fiber assembly (GO:0051496), response to electrical stimulus (GO:0051602), smooth muscle contraction involved in micturition (GO:0060083), positive regulation of uterine smooth muscle contraction (GO:0070474), positive regulation of flagellated sperm motility (GO:1902093)

GO Molecular Function (4): tachykinin receptor activity (GO:0004995), substance P receptor activity (GO:0016496), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), cell surface (GO:0009986), dendrite (GO:0030425), sperm flagellum (GO:0036126), cell body (GO:0044297), postsynaptic membrane (GO:0045211), sperm head (GO:0061827), sperm midpiece (GO:0097225), membrane (GO:0016020), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
G protein-coupled receptor signaling pathway	3
positive regulation of cell migration	2
tachykinin receptor signaling pathway	2
positive regulation of synaptic transmission	2
behavior	1
positive regulation of immune system process	1
regulation of leukocyte migration	1
leukocyte migration	1
brain renin-angiotensin system	1
drinking behavior	1
defense response	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
regulation of biological quality	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
memory	1
learning	1
response to abiotic stimulus	1
detection of stimulus	1
response to reactive oxygen species	1
epithelial cell migration	1
regulation of epithelial cell migration	1
response to mechanical stimulus	1
smooth muscle cell migration	1
regulation of cell migration	1
synaptic transmission, cholinergic	1
regulation of synaptic transmission, cholinergic	1
regulation of synaptic transmission, GABAergic	1
synaptic transmission, GABAergic	1
response to lipid	1
response to oxygen-containing compound	1
response to steroid hormone	1
response to ketone	1
neuropeptide receptor activity	1
tachykinin receptor activity	1
transmembrane signaling receptor activity	1
binding	1
membrane	1

Protein interactions and networks

STRING

1236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TACR1	TAC1	P20366	999
TACR1	TAC3	Q9UHF0	996
TACR1	TAC4	Q86UU9	941
TACR1	ARRB2	P32121	918
TACR1	ARRB1	P49407	918
TACR1	NALCN	Q8IZF0	874
TACR1	UNC80	Q8N2C7	853
TACR1	NTS	P30990	849
TACR1	VIP	P01282	742
TACR1	TRPV1	Q8NER1	736
TACR1	SST	P01166	721
TACR1	CHKB	Q9Y259	708
TACR1	OPRM1	P35372	707
TACR1	MME	P08473	669
TACR1	TRPC7	Q9HCX4	644

IntAct

15 interactions, top by confidence:

A	B	Type	Score
TACR1	ATP5PB	psi-mi:“MI:0914”(association)	0.640
TACR1	CCDC167	psi-mi:“MI:0915”(physical association)	0.560
TACR1	TMEM147	psi-mi:“MI:0915”(physical association)	0.560
TACR1	TAC1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	TACR1	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	TACR1	psi-mi:“MI:0915”(physical association)	0.400
TACR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
TACR1	B3GAT3	psi-mi:“MI:0914”(association)	0.350
CCDC167	TACR1	psi-mi:“MI:0915”(physical association)	0.000
TMEM147	TACR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (99): TACR1 (Reconstituted Complex), TACR1 (Reconstituted Complex), RDH14 (Affinity Capture-MS), CAV1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), SLMAP (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), PKP2 (Affinity Capture-MS), ARVCF (Affinity Capture-MS), COX1 (Affinity Capture-MS), GPR89A (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ATP8 (Affinity Capture-MS), MFSD5 (Affinity Capture-MS), NDUFS6 (Affinity Capture-MS)

ESM2 similar proteins: A5A4L1, B2ZI34, O08725, O54799, O62709, P14600, P21450, P21451, P21729, P24053, P24530, P25101, P25103, P26684, P28088, P28336, P30547, P30548, P30550, P32304, P32305, P33534, P33535, P34975, P35372, P35463, P41144, P41145, P42866, P47211, P48302, P52500, P56479, P56497, P79350, Q29010, Q2KIP6, Q5DUB3, Q5IS39, Q5IS84

Diamond homologs: A0T2N3, A1ZAX0, E7F7V7, F1MV99, F1R332, O08726, O08858, O43603, O60755, O88626, O88853, O88854, O97666, P14600, P21109, P25024, P25025, P25103, P28646, P30547, P30548, P30680, P30731, P30872, P30873, P30874, P30875, P30937, P30938, P30974, P30975, P31391, P32300, P32303, P32745, P33396, P33533, P33534, P33535, P34975

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
TACR1	“up-regulates activity”	GNAS	binding
TACR1	“up-regulates activity”	GNAL	binding
TACR1	“up-regulates activity”	GNAI1	binding
TACR1	“up-regulates activity”	GNAI3	binding
TACR1	“up-regulates activity”	GNAO1	binding
TACR1	“up-regulates activity”	GNAZ	binding
TACR1	“up-regulates activity”	GNAQ	binding
TACR1	“up-regulates activity”	GNA14	binding
“Substance P”	“up-regulates activity”	TACR1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	7
Uncertain significance	131
Likely benign	82
Benign	8

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1162322	NM_003124.5(SPR):c.304+2_304+13del	Pathogenic
12939	NM_003124.5(SPR):c.355C>T (p.Gln119Ter)	Pathogenic
12940	NM_003124.5(SPR):c.448_452del (p.Thr151fs)	Pathogenic
12941	NM_003124.5(SPR):c.448A>G (p.Arg150Gly)	Pathogenic
12943	NM_003124.5(SPR):c.488C>T (p.Pro163Leu)	Pathogenic
12944	NM_003124.5(SPR):c.751A>T (p.Lys251Ter)	Pathogenic
1323647	NM_003124.5(SPR):c.544C>T (p.Gln182Ter)	Pathogenic
1458146	NC_000002.11:g.(?73114562)(73115753_?)del	Pathogenic
2165411	NM_003124.5(SPR):c.277C>T (p.Gln93Ter)	Pathogenic
235551	NM_003124.5(SPR):c.655C>T (p.Arg219Ter)	Pathogenic
2720176	NM_003124.5(SPR):c.715C>T (p.Gln239Ter)	Pathogenic
2760535	NM_003124.5(SPR):c.262del (p.Arg88fs)	Pathogenic
31917	NM_003124.5(SPR):c.304G>T (p.Gly102Cys)	Pathogenic
3617711	NM_003124.5(SPR):c.619C>T (p.Gln207Ter)	Pathogenic
39869	NM_003124.5(SPR):c.596-2A>G	Pathogenic
429901	NM_003124.5(SPR):c.369C>G (p.Tyr123Ter)	Pathogenic
522878	NM_003124.4(SPR):c.596del	Pathogenic
625209	NM_003124.5(SPR):c.305-2A>G	Pathogenic
831031	NC_000002.12:g.(?72887413)(72891557_?)del	Pathogenic
842660	NM_003124.5(SPR):c.615dup (p.Gln206fs)	Pathogenic
985237	NM_003124.5(SPR):c.587A>G (p.Tyr196Cys)	Pathogenic
1162323	NM_003124.5(SPR):c.512G>A (p.Cys171Tyr)	Likely pathogenic
1414432	NM_003124.5(SPR):c.596-2_602del	Likely pathogenic
1698420	NM_003124.5(SPR):c.1A>C (p.Met1Leu)	Likely pathogenic
2502832	NM_003124.5(SPR):c.631del (p.Glu211fs)	Likely pathogenic
2627381	NM_003124.5(SPR):c.560A>G (p.Glu187Gly)	Likely pathogenic
444507	NM_003124.5(SPR):c.783_786del (p.Ter262ProextTer?)	Likely pathogenic
808769	NM_003124.5(SPR):c.517G>T (p.Gly173Ter)	Likely pathogenic

SpliceAI

1236 predictions. Top by Δscore:

Variant	Effect	Δscore
2:75051245:CCTCA:C	donor_loss	1.0000
2:75051246:CTCAC:C	donor_loss	1.0000
2:75051247:TCAC:T	donor_loss	1.0000
2:75051248:CACCT:C	donor_loss	1.0000
2:75051249:A:C	donor_loss	1.0000
2:75051250:C:A	donor_loss	1.0000
2:75051444:CCAC:C	acceptor_gain	1.0000
2:75051445:CAC:C	acceptor_gain	1.0000
2:75051445:CACC:C	acceptor_gain	1.0000
2:75051446:AC:A	acceptor_gain	1.0000
2:75051447:CC:C	acceptor_gain	1.0000
2:75051447:CCT:C	acceptor_loss	1.0000
2:75051449:T:A	acceptor_loss	1.0000
2:75053600:CTCA:C	donor_loss	1.0000
2:75053601:TCA:T	donor_loss	1.0000
2:75053602:CA:C	donor_loss	1.0000
2:75053603:ACCT:A	donor_loss	1.0000
2:75053604:C:CA	donor_loss	1.0000
2:75053751:GGTAC:G	acceptor_gain	1.0000
2:75053752:GTACC:G	acceptor_loss	1.0000
2:75053753:TAC:T	acceptor_gain	1.0000
2:75053753:TACC:T	acceptor_loss	1.0000
2:75053754:AC:A	acceptor_gain	1.0000
2:75053755:CC:C	acceptor_gain	1.0000
2:75053755:CCT:C	acceptor_loss	1.0000
2:75053756:C:CC	acceptor_gain	1.0000
2:75053757:T:A	acceptor_loss	1.0000
2:75053760:A:T	acceptor_gain	1.0000
2:75120572:A:AC	donor_gain	1.0000
2:75120573:C:CC	donor_gain	1.0000

AlphaMissense

2679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:75051295:G:C	S296R	1.000
2:75051295:G:T	S296R	1.000
2:75051297:T:G	S296R	1.000
2:75051412:G:C	F257L	1.000
2:75051412:G:T	F257L	1.000
2:75051414:A:G	F257L	1.000
2:75120606:C:A	W184C	1.000
2:75120606:C:G	W184C	1.000
2:75120618:G:C	C180W	1.000
2:75120619:C:G	C180S	1.000
2:75120619:C:T	C180Y	1.000
2:75120620:A:T	C180S	1.000
2:75120695:A:G	W155R	1.000
2:75120695:A:T	W155R	1.000
2:75198546:C:A	R130M	1.000
2:75198621:C:G	C105S	1.000
2:75198621:C:T	C105Y	1.000
2:75198622:A:T	C105S	1.000
2:75198641:C:A	W98C	1.000
2:75198641:C:G	W98C	1.000
2:75198643:A:G	W98R	1.000
2:75198643:A:T	W98R	1.000
2:75049720:G:C	F312L	0.999
2:75049720:G:T	F312L	0.999
2:75049721:A:G	F312S	0.999
2:75049722:A:G	F312L	0.999
2:75051280:G:C	N301K	0.999
2:75051280:G:T	N301K	0.999
2:75051309:A:G	W292R	0.999
2:75051309:A:T	W292R	0.999

dbSNP variants (sampled 300 via entrez): RS1000002603 (2:75095303 G>A), RS1000010907 (2:75175734 C>G,T), RS1000030359 (2:75055427 G>A,T), RS1000040533 (2:75073924 A>G), RS1000061392 (2:75055681 T>C), RS1000065265 (2:75136893 T>C), RS1000071029 (2:75178136 C>G,T), RS1000073018 (2:75047861 T>C), RS1000114214 (2:75053004 A>C,G), RS1000164140 (2:75153860 C>T), RS1000198299 (2:75083211 G>A), RS1000203642 (2:75193738 C>G), RS1000215289 (2:75089287 C>G,T), RS1000216003 (2:75153574 G>T), RS1000243998 (2:75107840 A>G)

Disease associations

OMIM: gene MIM:162323 | disease phenotypes: MIM:612716

GenCC curated gene-disease

Disease	Classification	Inheritance
dopa-responsive dystonia due to sepiapterin reductase deficiency	Definitive	Autosomal recessive
BH4-deficient hyperphenylalaninemia A	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dopa-responsive dystonia due to sepiapterin reductase deficiency	Definitive	AR

Mondo (4): dystonic disorder (MONDO:0003441), dopa-responsive dystonia due to sepiapterin reductase deficiency (MONDO:0012994), intellectual disability (MONDO:0001071), BH4-deficient hyperphenylalaninemia A (MONDO:0009863)

Orphanet (3): Dopa-responsive dystonia due to sepiapterin reductase deficiency (Orphanet:70594), Non-syndromic anorectal malformation (Orphanet:557), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001332	Dystonia

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001889_11	Brain connectivity	3.000000e-09
GCST002063_6	Sexual dimorphism in anthropometric traits	9.000000e-07
GCST002875_158	Diisocyanate-induced asthma	4.000000e-09
GCST005024_51	Pursuit maintenance gain	2.000000e-06
GCST005655_3	Seborrheic dermatitis	1.000000e-07
GCST007094_72	Diastolic blood pressure	2.000000e-09
GCST007099_71	Systolic blood pressure	4.000000e-06
GCST007250_3	Nonunion in individuals with fractures	3.000000e-07
GCST007576_126	Chronotype	1.000000e-09
GCST008152_82	Weight	3.000000e-06
GCST010277_16	Gout	9.000000e-07
GCST010725_60	Malaria	7.000000e-06
GCST010725_79	Malaria	5.000000e-06
GCST012307_5	Bipolar disorder x sex interaction	5.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0005951	sexual dimorphism
EFO:0006995	response to diisocyanate
EFO:0008433	pursuit maintenance gain measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009707	fractures, ununited
EFO:0008328	chronotype measurement
EFO:0004338	body weight
EFO:0008343	sex interaction measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D020821	Dystonic Disorders	C10.228.662.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C535325	6-pyruvoyl-tetrahydropterin synthase deficiency (supp.)
C562657	Dystonia, Dopa-Responsive, due to Sepiapterin Reductase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL249 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

42 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 631,392 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1255800	FIDAXOMICIN	4	2,010
CHEMBL1471	APREPITANT	4	901
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL163	RITONAVIR	4	53,773
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL206253	NETUPITANT	4	2,133
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL3707331	ROLAPITANT	4	980
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL490	PAROXETINE	4	46,410
CHEMBL52440	DEXTROMETHORPHAN	4	33,223
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL551466	ACLIDINIUM BROMIDE	4	247
CHEMBL621	TRAZODONE	4	26,657
CHEMBL623	NEFAZODONE	4
CHEMBL64391	ITRACONAZOLE	4
CHEMBL707	DOXAZOSIN	4
CHEMBL723	CARVEDILOL	4
CHEMBL808	ECONAZOLE	4
CHEMBL83	TAMOXIFEN	4
CHEMBL91	MICONAZOLE	4
CHEMBL1672054	CASOPITANT	3
CHEMBL308148	SAREDUTANT	3
CHEMBL447955	SERLOPITANT	3

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs735668	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

14 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2111375	TACR1		0.00	0
rs6715729	TACR1		0.00	0
rs881	TACR1		0.00	0
rs4439987	TACR1		0.00	0
rs6546952	TACR1		0.00	0
rs2160652	TACR1		0.00	0
rs12475818	TACR1		0.00	0
rs3771836	TACR1		0.00	0
rs10191107	TACR1		0.00	0
rs12713837	TACR1		0.00	0
rs6725334	TACR1		0.00	0
rs2024512	TACR1		0.00	0
rs735668	TACR1	3	2.00	1	opioids
rs58933792	TACR1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Tachykinin receptors

Most potent curated ligand interactions (52 total), top 25:

Ligand	Action	Affinity	Parameter
hemokinin 1	Full agonist	11.7	pKi
vofopitant	Antagonist	10.6	pKi
substance P	Full agonist	10.3	pKi
serlopitant	Antagonist	10.22	pIC50
T2328	Antagonist	10.1	pKi
aprepitant	Antagonist	10.05	pKi
lanepitant	Antagonist	10.0	pKi
ZD6021	Antagonist	9.9	pIC50
[Sar9,Met(O2)11]SP	Full agonist	9.9	pIC50
L760735	Antagonist	9.72	pIC50
ezlopitant	Antagonist	9.7	pKi
CP 99994	Antagonist	9.7	pKi
[125I]L703,606	Antagonist	9.5	pKd
casopitant	Antagonist	9.4	pKi
vestipitant	Antagonist	9.37	pKi
TAK-637	Antagonist	9.35	pIC50
R116031	Antagonist	9.35	pKi
septide	Full agonist	9.3	pKi
neurokinin A	Full agonist	9.3	pKi
imnopitant	Antagonist	9.24	pKi
physalaemin	Full agonist	9.2	pIC50
rolapitant	Antagonist	9.18	pKi
L-733,060	Antagonist	9.1	pKi
FK-888	Antagonist	9.1	pKi
netupitant	Antagonist	9.02	pKi

Binding affinities (BindingDB)

176 measured of 182 human assays (196 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
ZD6021	KI	0.12 nM
4-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-[1-(2-hydroxyacetyl)piperidine-4-carbonyl]piperidin-4-yl]-N-methylbenzamide	IC50	0.22 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3R,4R)-1-[(1-acetylpiperidin-4-yl)methyl]-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamide	IC50	0.22 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-[1-(2-hydroxyacetyl)piperidine-4-carbonyl]piperidin-4-yl]-N-methyl-4-(trifluoromethyl)benzamide	IC50	0.22 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methyl-4-(trifluoromethyl)benzamide	IC50	0.23 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
4-bromo-N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-[1-(2-hydroxyacetyl)piperidine-4-carbonyl]piperidin-4-yl]-N-methylbenzamide	IC50	0.24 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-cyclopropyl-N-methylbenzamide	IC50	0.25 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
SCH 206272	KI	0.3 nM
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamide	IC50	0.31 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-[1-(2-hydroxyacetyl)piperidine-4-carbonyl]piperidin-4-yl]-N-methyl-5-(trifluoromethyl)pyridine-2-carboxamide	IC50	0.36 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
CHEMBL120523	IC50	0.363 nM
N-[(4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-bromo-N-methylbenzamide	IC50	0.45 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-6-(2-methyl-2H-tetrazol-5-yl)-1-phenyl-8-aza-bicyclo[3.2.1]octane	IC50	0.5 nM
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-methoxy-N-methylbenzamide	IC50	0.56 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
CHEMBL340559	IC50	0.617 nM
CHEMBL2114439	KI	0.631 nM
Substance P [Sar9,Met(O2)11]	KI	0.65 nM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-acetamido-3-(1H-indol-3-yl)propanoate	KI	0.73 nM
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide	IC50	0.79 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-5-bromo-N-methylpyridine-2-carboxamide	IC50	0.82 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
SB-2234	KI	1 nM
2-(3,5-bis(trifluoromethyl)benzyloxy)-6-(2-methyl-2H-tetrazol-5-yl)-1-phenyl-8-aza-bicyclo[3.2.1]octane	IC50	1 nM
N-[(4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamide	IC50	1.1 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-aza-bicyclo[3.2.1]octane	IC50	1.2 nM
2-(3,5-bis(trifluoromethyl)benzyloxy)-6-fluoro-6-(2-methyl-2H-tetrazol-5-yl)-1-phenyl-8-aza-bicyclo[3.2.1]octane	IC50	1.5 nM
L-703606	IC50	1.6 nM
N-[(4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methyl-4-phenylbenzamide	IC50	1.7 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N,4-dimethylbenzamide	IC50	2 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(3S)-1-(1-acetylpiperidine-4-carbonyl)-4-(3,4-dichlorophenyl)pyrrolidin-3-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide	IC50	2.2 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
N-[(4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-methoxy-N-methylbenzamide	IC50	2.3 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
1-[3,5-bis(trifluoromethyl)phenyl]-3-[(3S,4R)-4-(4-fluorophenyl)-1-[1-(2-hydroxy-2-methylpropanoyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-1,3-dimethylurea	IC50	2.4 nM	US-8592454: Nitrogen-containing heterocyclic compound and use of same
CHEMBL2392023	KI	2.6 nM
2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-1-phenyl-8-aza-bicyclo[3.2.1]octane	IC50	4.2 nM
2-[4-[5-[[2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl]-methylamino]-4-(4-fluoro-2-methylphenyl)-6-(hydroxymethyl)-2-pyridinyl]cyclohexyl]acetic acid	IC50	4.96 nM	US-9708266: Cyclohexyl pyridine derivative
[(8R)-3-(3-ethyl-1,2,4-oxadiazol-5-yl)-8-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	5 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
[(8R)-3-[2-(dimethylamino)-1,3-thiazol-4-yl]-8-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	7 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
1-[(3R,4S)-1-(1-acetylpiperidine-4-carbonyl)-4-(4-fluorophenyl)pyrrolidin-3-yl]-3-[3,5-bis(trifluoromethyl)phenyl]-1,3-dimethylurea	IC50	7.1 nM	US-8592454: Nitrogen-containing heterocyclic compound and use of same
2-(3,5-bis(trifluoromethyl)benzyloxy)-6-(1-methyl-1H-tetrazol-5-yl)-1-phenyl-8-aza-bicyclo[3.2.1]octane	IC50	9 nM
H-Tyr-D-Ala-Gly-Phe-Pro-Leu-Trp-NH-Bzl	KI	10 nM
[(8R)-8-methyl-3-(6-methyl-2-pyridinyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	11 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
[(8R)-3-(3-ethyl-1,2,4-thiadiazol-5-yl)-8-methyl-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-fluorophenyl)methanone	IC50	12 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
(3,4-dichlorophenyl)-[(8R)-8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	16 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
[(8R)-8-methyl-3-(2-methyl-1,3-thiazol-4-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	16 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
(S)-N-{(S)-1-[(S)-1-({[(S)-1-((S)-1-Carbamoyl-3-methylsulfanyl-propylcarbamoyl)-3-methyl-butylcarbamoyl]-methyl}-carbamoyl)-2-phenyl-ethylcarbamoyl]-2-phenyl-ethyl}-3-(3-carboxy-propionylamino)-N-methyl-succinamic acid	KI	17.1 nM
6-[(8R)-8-methyl-7-(4-thiophen-2-ylbenzoyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-3-yl]-1H-pyridin-2-one	IC50	18 nM	US-9475814: Chiral N-acyl-5,6,7(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor mediated disorders and chiral synthesis thereof
fezolinetant	IC50	18 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
(4-chloro-3-fluorophenyl)-[(8R)-8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	19 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
(4-fluorophenyl)-[(8R)-8-methyl-3-[2-(trifluoromethyl)-1,3-thiazol-4-yl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	20 nM	US-9840508: N-acyl-(3-substituted)-(8-methyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a] pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor-mediated disorders
(3,4-difluorophenyl)-[(8R)-8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	21 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
(3-chloro-4-fluorophenyl)-[(8R)-8-methyl-3-[2-(trifluoromethyl)-1,3-thiazol-4-yl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	23 nM	US-9840508: N-acyl-(3-substituted)-(8-methyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a] pyrazines as selective NK-3 receptor antagonists, pharmaceutical composition, methods for use in NK-3 receptor-mediated disorders

ChEMBL bioactivities

3192 potent at pChembl≥5 of 3280 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL1270066
11.00	IC50	0.01	nM	CHEMBL281797
10.96	IC50	0.011	nM	CHEMBL26761
10.92	IC50	0.012	nM	CHEMBL3215877
10.91	IC50	0.0123	nM	CHEMBL1214024
10.90	IC50	0.01259	nM	CHEMBL507340
10.89	IC50	0.013	nM	CHEMBL1092755
10.80	Ki	0.016	nM	CHEMBL3609620
10.77	IC50	0.017	nM	CHEMBL1917864
10.77	IC50	0.017	nM	CHEMBL1951813
10.74	IC50	0.0182	nM	CHEMBL1766208
10.70	Ki	0.02	nM	CHEMBL212428
10.70	IC50	0.02	nM	CHEMBL1951810
10.60	Ki	0.02512	nM	VOFOPITANT DIHYDROCHLORIDE
10.60	IC50	0.025	nM	CHEMBL1917866
10.57	IC50	0.027	nM	CHEMBL3651897
10.54	IC50	0.029	nM	CHEMBL3651891
10.52	Ki	0.03	nM	CHEMBL3609617
10.52	IC50	0.03	nM	CHEMBL3651896
10.52	IC50	0.03	nM	CHEMBL392466
10.52	Kd	0.0302	nM	VESTIPITANT
10.52	IC50	0.03	nM	CHEMBL413027
10.51	IC50	0.031	nM	CHEMBL3651887
10.50	Ki	0.03162	nM	CHEMBL149557
10.49	IC50	0.032	nM	CHEMBL3651892
10.49	IC50	0.032	nM	CHEMBL1951626
10.47	Ki	0.034	nM	CHEMBL2419537
10.46	IC50	0.035	nM	CHEMBL1951633
10.41	IC50	0.039	nM	CHEMBL3651895
10.41	IC50	0.039	nM	CHEMBL1917853
10.40	Ki	0.03981	nM	CHEMBL542044
10.40	Ki	0.03981	nM	CHEMBL555572
10.40	Ki	0.03981	nM	CHEMBL545594
10.40	IC50	0.04	nM	CHEMBL555572
10.40	IC50	0.04	nM	CHEMBL1091469
10.39	IC50	0.041	nM	CHEMBL1089271
10.37	IC50	0.043	nM	CHEMBL1951631
10.36	IC50	0.044	nM	CHEMBL1917856
10.34	Ki	0.046	nM	CHEMBL261390
10.34	IC50	0.046	nM	CHEMBL1951811
10.33	IC50	0.047	nM	CHEMBL1951630
10.32	IC50	0.048	nM	CHEMBL1951632
10.31	IC50	0.049	nM	CHEMBL3651893
10.31	EC50	0.04898	nM	CHEMBL1627325
10.31	IC50	0.049	nM	CHEMBL1917852
10.30	IC50	0.05	nM	CHEMBL99055
10.30	Ki	0.05012	nM	CHEMBL536103
10.30	Ki	0.05012	nM	CHEMBL545360
10.30	Ki	0.05	nM	CHEMBL3608937
10.30	IC50	0.05	nM	CHEMBL391615

PubChem BioAssay actives

2730 with measured affinity, of 4117 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
3-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-3-phenylcyclobutan-1-amine	268445: Displacement of [3H]Sar-Met substance P from human recombinant NK1 receptor expressed in CHO cells	ki	<0.0001	uM
N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(hydroxymethyl)-4-phenylquinoline-3-carboxamide	208276: Binding affinity against human Tachykinin receptor 1 expressed in astrocytoma UC11MG cells using [125I]- SP radioligand	ic50	<0.0001	uM
(2S,3S)-N-[(2-methoxy-5-thiophen-3-ylphenyl)methyl]-2-phenylpiperidin-3-amine	208598: Binding affinity to Tachykinin receptor 1 stably expressed in chinese hamster ovary (CHO) cells	ki	<0.0001	uM
2-(aminomethyl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-phenylquinoline-3-carboxamide	208276: Binding affinity against human Tachykinin receptor 1 expressed in astrocytoma UC11MG cells using [125I]- SP radioligand	ic50	<0.0001	uM
N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(bromomethyl)-4-phenylquinoline-3-carboxamide	208276: Binding affinity against human Tachykinin receptor 1 expressed in astrocytoma UC11MG cells using [125I]- SP radioligand	ic50	<0.0001	uM
N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-N-methyl-4-phenylquinoline-3-carboxamide	208276: Binding affinity against human Tachykinin receptor 1 expressed in astrocytoma UC11MG cells using [125I]- SP radioligand	ic50	<0.0001	uM
N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-(methylaminomethyl)-4-phenylquinoline-3-carboxamide	208276: Binding affinity against human Tachykinin receptor 1 expressed in astrocytoma UC11MG cells using [125I]- SP radioligand	ic50	<0.0001	uM
(3S,4S)-1-(1-acetylpiperidine-4-carbonyl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
N-[2-[(3R,4S)-4-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methylamino]-3-phenylpiperidin-1-yl]-2-oxoethyl]acetamide	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]acetyl]amino]-3-(1H-indol-3-yl)propanoate	1242772: Displacement of [3H]-substance P from human NK1 receptor transfected in CHO cells	ki	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoate	1242772: Displacement of [3H]-substance P from human NK1 receptor transfected in CHO cells	ki	<0.0001	uM
(2S,3S)-N-[[2-methoxy-5-(tetrazol-1-yl)phenyl]methyl]-2-phenylpiperidin-3-amine;dihydrochloride	779964: Antagonist activity at NK1 receptor (unknown origin)	ic50	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1798027: Radioligand Labeled Binding Assay from Article 10.1021/jm070332f: “A Structure-Activity Relationship Study and Combinatorial Synthetic Approach of C-Terminal Modified Bifunctional Peptides That Are delta/mu Opioid Receptor Agonists and Neurokinin 1 Receptor Antagonists.”	ki	<0.0001	uM
(3S,4S)-N-[(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-3-(4-fluoro-2-methylphenyl)-N-methyl-1-oxamoylpiperidine-4-carboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(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-methylsulfanylbutanoyl]-N-[(2S)-1-[[(2S)-1-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	391166: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cell membrane by liquid scintillation counting	ki	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoate	1242772: Displacement of [3H]-substance P from human NK1 receptor transfected in CHO cells	ki	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-(1H-indol-3-yl)propanoate	1242772: Displacement of [3H]-substance P from human NK1 receptor transfected in CHO cells	ki	<0.0001	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]hexanoyl]-N-[(2S)-1-[[(2S)-1-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	422079: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cell membrane	ic50	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	766404: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cells	ki	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	766404: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cells	ki	<0.0001	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]-N-[(2S)-1-[[(2S)-1-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	592526: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cells	ic50	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2R)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-hydroxypropanoic acid	375519: Antagonist activity at human recombinant NK1 receptor expressed in CHO cells assessed as inhibition of NPS-induced intracellular calcium mobilization	ec50	<0.0001	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropanoyl]-N-[(2S)-1-[[(2S)-1-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	422079: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cell membrane	ic50	<0.0001	uM
1-[4-[(3S,4R)-3-[5-[2-[3,5-bis(trifluoromethyl)phenyl]propan-2-yl]-1,2,4-oxadiazol-3-yl]-4-(4-fluoro-2-methylphenyl)pyrrolidine-1-carbonyl]piperidin-1-yl]ethanone	301059: Displacement of [125I]SP from human NK1 receptor expressed in CHO cells	ic50	<0.0001	uM
(6R,7S,8S)-6-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-7-(4-fluorophenyl)-2-hydroxy-2-methyl-5,6,7,8-tetrahydro-1H-pyrrolizin-3-one	463576: Displacement of [125I]substance P from human NK1 receptor expressed in CHO cells	ic50	<0.0001	uM
(1S,2R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-7-(1-tert-butylpiperidin-4-yl)-1-(4-fluorophenyl)-2,3,8,8a-tetrahydro-1H-indolizin-5-one	473682: Displacement of [125I]substance P from human NK1 receptor expressed in CHO cells	ic50	<0.0001	uM
(1S,2R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-1-(4-fluorophenyl)-2,3,8,8a-tetrahydro-1H-indolizin-5-one	473682: Displacement of [125I]substance P from human NK1 receptor expressed in CHO cells	ic50	<0.0001	uM
(2S)-1-[(4S,7S,13R)-13-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carbonyl]-N-[(2S)-1-[[(2S)-1-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	497529: Displacement of [3H]substance P frome human NK1 receptor	ki	<0.0001	uM
(3S,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-N-methyl-1-oxamoylpiperidine-4-carboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
N-[4-[(3R,4S)-4-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methylamino]-3-phenylpiperidin-1-yl]-4-oxobutyl]acetamide;hydrochloride	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3S,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-1-[2-(hydroxyamino)-2-oxoacetyl]-N-methylpiperidine-4-carboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3S,4S)-4-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-1-N,4-N-dimethylpiperidine-1,4-dicarboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3S,4S)-1-(2-acetamidoacetyl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
1-[(3R,4S)-4-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methylamino]-3-phenylpiperidin-1-yl]ethanone;hydrochloride	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3R,4S)-4-[[2-cyclopropyloxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methylamino]-N-ethyl-3-phenylpiperidine-1-carboxamide;hydrochloride	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3S,4S)-1-(1-acetylpiperidine-4-carbonyl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-N-methyl-3-(2-methylphenyl)piperidine-4-carboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3S,4S)-4-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-(4-fluoro-2-methylphenyl)-4-N-methylpiperidine-1,4-dicarboxamide	646565: Displacement of [125I]BH-SP from tachykinin NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(2S,3S)-N-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine;dihydrochloride	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ki	<0.0001	uM
[3,5-bis(trifluoromethyl)phenyl]methyl (2S)-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-3-(1H-indol-3-yl)propanoate	766404: Displacement of [3H]substance P from human NK1 receptor expressed in CHO cells	ki	<0.0001	uM
(2S,3S)-N-[[2-methoxy-5-(trifluoromethoxy)phenyl]methyl]-2-phenylpiperidin-3-amine;dihydrochloride	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(3R,4S)-N-ethyl-4-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methylamino]-3-phenylpiperidine-1-carboxamide;hydrochloride	630278: Displacement of [125I]BH-SP from NK1 receptor in human IM9 cells after 30 mins by scintillation counting	ic50	<0.0001	uM
(2S)-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperazine-1-carboxamide	350144: Binding affinity to human recombinant NK1 receptor expressed in CHO cells assessed as dissociation constant	kd	<0.0001	uM
(3S)-3-[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]-10-phenyl-1-oxa-9-azaspiro[4.5]decane	208415: Displacement of [125I]-labeled substance P from the cloned human Tachykinin receptor 1 expressed in CHO cells	ic50	0.0001	uM
3-[2-(4-chlorophenyl)-1,5-dimethylindol-3-yl]-1-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-one	144534: Concentration required for displacement of [125I]-labeled substance P from cloned hNK1 receptor expressed in CHO cells(*).	ic50	0.0001	uM
3-[2-(4-bromophenyl)-1,5-dimethylindol-3-yl]-1-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-one	144534: Concentration required for displacement of [125I]-labeled substance P from cloned hNK1 receptor expressed in CHO cells(*).	ic50	0.0001	uM
1-(4-benzyl-4-hydroxypiperidin-1-yl)-3-[5-chloro-1-methyl-2-[5-(trifluoromethyl)-2-pyridinyl]indol-3-yl]propan-1-one	144534: Concentration required for displacement of [125I]-labeled substance P from cloned hNK1 receptor expressed in CHO cells(*).	ic50	0.0001	uM
(2S,3S)-N-[[2-ethoxy-5-(trifluoromethoxy)phenyl]methyl]-2-phenylpiperidin-3-amine	208265: Antagonist activity for Tachykinin receptor 1 as displacement of [3H]-Substance P in human IM-9 cells	ic50	0.0001	uM
(2R,4S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(dimethylamino)-2-(4-fluoro-2-methylphenyl)-N-methylpiperidine-1-carboxamide	576859: Displacement of [3H]SP from human NK1 receptor expressed in CHO cells by liquid scintillation counting	ki	0.0001	uM
N-[3-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-3-phenylcyclobutyl]acetamide	268445: Displacement of [3H]Sar-Met substance P from human recombinant NK1 receptor expressed in CHO cells	ki	0.0001	uM
1-(4-benzyl-4-hydroxypiperidin-1-yl)-3-[5-chloro-2-(4-chlorophenyl)-1-methylpyrrolo[2,3-b]pyridin-3-yl]propan-1-one	144533: Concentration required for displacement of [125I]-labeled substance P from cloned hNK1 receptor expressed in CHO cells	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases methylation	2
Aprepitant	affects binding, decreases activity	2
Asian ginseng	affects cotreatment, decreases expression	1
VX-agent	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
manganese chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
substance P, Sar(9)-Met(O2)(11)-	decreases reaction, increases activity	1
CGP 52608	affects binding, increases reaction	1
S 18523	affects binding	1
vofopitant	affects binding, decreases reaction	1
3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine	decreases reaction, increases activity	1
SU 5402	decreases expression, decreases reaction, increases expression	1
R116301	affects binding	1
bardoxolone methyl	decreases activity	1
clothianidin	increases expression	1
(N-N’-bis-(2-(1H-indol-3-yl)-ethyl)-N,N’-bis-(3-thiomorpholin-4-yl-propyl)-phthalamide)	affects binding	1
casopitant	affects binding, decreases activity, decreases reaction	1
vestipitant	affects binding, decreases activity	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases expression	1
Diethylhexyl Phthalate	affects cotreatment, decreases expression	1
Dobutamine	affects binding, increases activity, increases reaction	1
Lipopolysaccharides	increases expression, affects response to substance	1
Manganese	decreases expression	1
Taurine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

620 unique, capped per target: 506 binding, 111 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000259	Binding	Displacement of [125I]substance P human recombinant NK1 receptor expressed in CHO cells in absence of human serum albumin	Potent, brain-penetrant, hydroisoindoline-based human neurokinin-1 receptor antagonists. — J Med Chem
CHEMBL1001562	Functional	Antagonist activity at human recombinant NK1 receptor expressed in CHO cells assessed as inhibition of NPS-induced intracellular calcium mobilization	Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists. — J Med Chem
CHEMBL4726510	ADMET	Binding affinity to NK1R (unknown origin) expressed in HEK293 cells assessed as protein-mediated drug uptake at 1 uM incubated for 1 hr by flow cytometry analysis	Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P. — Bioorg Med Chem Lett

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D1QU	Abcam K-562 TACR1 KO	Cancer cell line	Female
CVCL_D2MF	Abcam Raji TACR1 KO	Cancer cell line	Male
CVCL_H470	CHO-K1/NK1	Spontaneously immortalized cell line	Female
CVCL_KW21	PathHunter C2C12 TACR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ17	PathHunter CHO-K1 TACR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB35	PathHunter U2OS TACR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_WQ63	Abcam Jurkat TACR1 KO	Cancer cell line	Male
CVCL_YK21	HEK293 TACR1 HiTSeeker	Transformed cell line	Female
CVCL_YK58	U2OS TACR1 calcium-Nomad	Cancer cell line	Female
CVCL_ZK24	Tango TACR1-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
NCT01433757	PHASE1	COMPLETED	Ampicillin for DYT-1 Dystonia Motor Symptoms
NCT01698450	PHASE1	COMPLETED	Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
NCT02982304	PHASE1	UNKNOWN	Multi-Target Pallidal and Thalamic Deep Brain Stimulation for Hemi-Dystonia
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06554288	PHASE1	RECRUITING	Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT00004421	PHASE2/PHASE3	COMPLETED	Deep Brain Stimulation in Treating Patients With Dystonia
NCT00272246	PHASE2/PHASE3	UNKNOWN	Bilateral Internal Pallidum Stimulation in Primary Generalized Dystonia
NCT00608231	PHASE2/PHASE3	WITHDRAWN	Dexmedetomidine Effects on Microelectrode Recording in Deep Brain Stimulation
NCT04277247	PHASE2/PHASE3	UNKNOWN	Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson’s Disease
NCT02015039	PHASE1/PHASE2	COMPLETED	Pilot Trial of Botulinum Toxin and Occupational Therapy for Writer’s Cramp
NCT02911103	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Deep Brain Stimulation Surgery for Focal Hand Dystonia
NCT04727177	EARLY_PHASE1	UNKNOWN	Precision-targeted Transcranial Magnetic Stimulation in the Treatment of Primary Dystonia
NCT00006336	Not specified	COMPLETED	Sensory Training to Treat Focal Dystonia
NCT00017875	Not specified	COMPLETED	Transcranial Magnetic Stimulation (TMS) Studies of Dystonia
NCT00029601	Not specified	COMPLETED	Surround Inhibition in Patients With Dystonia
NCT00031369	Not specified	TERMINATED	Brain Anatomy in Dystonia
NCT00047957	Not specified	COMPLETED	Brain Inhibition of Muscle Movement in Normal Volunteers
NCT00050024	Not specified	COMPLETED	Transcranial Magnetic Stimulation and Electrical Stimulation of Nerves to Study Focal Dystonia
NCT00072956	Not specified	COMPLETED	The Physiology of Tricks
NCT00082615	Not specified	COMPLETED	Neurophysiological Markers in Patients With Craniofacial Dystonia and Their Relatives
NCT00102999	Not specified	COMPLETED	Brain Function in Focal Dystonia