TACR2

Summary

TACR2 (tachykinin receptor 2, HGNC:11527) is a protein-coding gene on chromosome 10q22.1, encoding Substance-K receptor (P21452). This is a receptor for the tachykinin neuropeptide substance K (neurokinin A).

This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5’-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neuropeptide substance K, also referred to as neurokinin A.

Source: NCBI Gene 6865 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• Druggable target: yes — 47 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11527
Approved symbol	TACR2
Name	tachykinin receptor 2
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	SKR, NK2R
Ensembl gene	ENSG00000075073
Ensembl biotype	protein_coding
OMIM	162321
Entrez	6865

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000373306, ENST00000373307

RefSeq mRNA: 1 — MANE Select: NM_001057 NM_001057

CCDS: CCDS7293

Canonical transcript exons

ENST00000373306 — 5 exons

Exon	Start	End
ENSE00000501852	69407084	69407280
ENSE00000834254	69414945	69415139
ENSE00001096442	69408922	69409075
ENSE00001460089	69415932	69416918
ENSE00001460091	69403903	69405084

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 97.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4626 / max 69.3270, expressed in 113 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109797	0.2027	88
109803	0.1073	19
109802	0.0731	17
109800	0.0241	14
109798	0.0198	9
109799	0.0198	11
109801	0.0159	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	97.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.76	gold quality
lower esophagus	UBERON:0013473	91.64	gold quality
sigmoid colon	UBERON:0001159	89.70	gold quality
smooth muscle tissue	UBERON:0001135	88.16	gold quality
left uterine tube	UBERON:0001303	85.69	gold quality
colonic epithelium	UBERON:0000397	84.55	gold quality
esophagus	UBERON:0001043	82.78	gold quality
colon	UBERON:0001155	82.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.13	gold quality
large intestine	UBERON:0000059	81.78	gold quality
body of uterus	UBERON:0009853	81.23	gold quality
transverse colon	UBERON:0001157	80.03	gold quality
intestine	UBERON:0000160	79.72	gold quality
fundus of stomach	UBERON:0001160	79.26	gold quality
lower esophagus mucosa	UBERON:0035834	77.58	gold quality
myometrium	UBERON:0001296	76.18	gold quality
esophagus mucosa	UBERON:0002469	75.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.52	gold quality
small intestine	UBERON:0002108	74.81	gold quality
urinary bladder	UBERON:0001255	73.35	gold quality
gastrocnemius	UBERON:0001388	73.10	gold quality
triceps brachii	UBERON:0001509	72.39	gold quality
muscle of leg	UBERON:0001383	72.07	gold quality
gluteal muscle	UBERON:0002000	72.01	gold quality
orbitofrontal cortex	UBERON:0004167	70.83	gold quality
ectocervix	UBERON:0012249	70.74	gold quality
rectum	UBERON:0001052	70.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting TACR2, 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-340-5P	100.00	72.50	4437
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-6529-5P	97.85	66.47	673
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-4750-3P	96.65	64.38	512
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 23)

• Tachykinin NK2 receptors mediate smooth muscle contraction in human corpus cavernosum and spongiosum. (PMID:11906947)
• Identification of a tachykinin NK(2) receptor splice variant. (PMID:12427486)
• protease-activated receptor 2 agonists induced a contraction of murine intestinal smooth muscle that was mediated by nerves and requires both neurokinin 1 and 2 receptors (PMID:12801882)
• NK2 receptors are compartmentalized at the plasma membrane (PMID:15294896)
• Preprotachykinin-I peptides mediate autocrine proliferation of the neuroblastoma cells through both NK-1 and NK-2 receptors. (PMID:15690122)
• We propose that the N-terminus of NKA is exposed and accessible to the extracellular medium. Subsequent amino acids of the NKA peptide become progressively more buried residues up to approximately one-third of the transmembrane-spanning domain. (PMID:17402972)
• Data indicate that presynaptic and postsynaptic neuroneuronal and neuromuscular regulatory processes mediated by tachykinins via NK2r may occur for modulating human colonic motility. (PMID:17503489)
• Increased proportion of alveolar macrophages expressing neurokinin 2 receptor may be involved in the pathogenesis of COPD. (PMID:17532769)
• all three subtypes of NKRs are expressed in native human airway smooth muscle cells & IP3 levels are the primary mediators of NKR-stimulated initial [Ca2+]i increases, whereas store-operated Ca2+ channels mediate sustained phase of the [Ca2+]i increase. (PMID:18203813)
• NK2 receptors are involved in the neuroneuronal and neuromuscular processes regulating human colonic motility. (PMID:18219665)
• polymorphisms leading to the Ile23Thr and Arg375His amino acid exchanges are highly prevalent in the human TACR2 gene, but do affect the potency of the endogenous agonist NKA or small molecule antagonists with respect to intracellular Ca(2+) signalling (PMID:18601911)
• The prevalence of the TACR2 mRNA alpha isoform strongly suggests a major involvement of tachykinin NK(2) receptor in the regulation of human colonic functions. (PMID:18835556)
• This study demonistrated that no association of Tachykinin receptor 2 (TACR2) polymorphisms with Alzheimer’s disease. (PMID:19375820)
• NK2R-dependent neuropeptide signaling regulates Ag-specific T cell responses via activation of DC function (PMID:22474018)
• This study aims to explore the associations of polymorphisms in tachykinin, precursor 1 (TAC1), tachykinin receptor 1 (TACR1), and tachykinin receptor 2 (TACR2) genes and their interactions with the risk of colorectal cancer among Chinese population. (PMID:22733436)
• The occurrence of a profound alteration in NK receptor expression in RMDD is a novel finding that suggests NK-1R and NK-2R pathways as possible players in major depressive disorder. (PMID:23142211)
• Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells (PMID:26371842)
• expressed in mural granulosa and cumulus cells (PMID:27146034)
• Expression substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors are dysregulated in uterine leiomyomata. (PMID:27456549)
• This study revealed for the first time an increase of Mast Cells -nerve association and NK2R expression on Mast Cells during Allergic Rhinitis as well as nerve fibres containing receptors for mass cells. (PMID:28030866)
• Hemokinin-1 and substance P stimulate production of inflammatory cytokines and chemokines in human colonic mucosa via both NK1 and NK2 tachykinin receptors. (PMID:32600668)
• IFN-alpha/beta-mediated NK2R expression is related to the malignancy of colon cancer cells. (PMID:35561088)
• Deciphering specificity and cross-reactivity in tachykinin NK1 and NK2 receptors. (PMID:37944618)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tacr2	ENSDARG00000074509
mus_musculus	Tacr2	ENSMUSG00000020081
rattus_norvegicus	Tacr2	ENSRNOG00000050658
drosophila_melanogaster	TkR99D	FBGN0004622
drosophila_melanogaster	TkR86C	FBGN0004841
caenorhabditis_elegans		WBGENE00016761

Paralogs (33): PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), 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-K receptor — P21452 (reviewed: P21452)

Alternative names: NK-2 receptor, Neurokinin A receptor, Tachykinin receptor 2

All UniProt accessions (2): P21452, A6NEW7

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_001048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000913	NK2_rcpt	Family
IPR001681	Neurokn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (65 total): helix 19, topological domain 8, transmembrane region 7, mutagenesis site 7, sequence variant 6, sequence conflict 5, turn 5, strand 3, glycosylation site 2, chain 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7XWO	ELECTRON MICROSCOPY	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21452-F1	80.63	0.51

Antibody-complex structures (SAbDab): 1 — 7XWO

Functional residue map

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

Post-translational modifications (1): 324

Disulfide bonds (1): 106–181

Glycosylation sites (2): 11, 19

Mutagenesis-validated functional residues (7):

Position	Phenotype
28	reduced response to nka.
93	reduced response to nka.
97	severely reduced response to nka.
114	reduced response to nka.
175	reduced response to nka.
285	reduced response to nka.
289	reduced response to nka.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380095	Tachykinin receptors bind tachykinins
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 171 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_HORMONE_TRANSPORT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (19): muscle contraction (GO:0006936), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating tachykinin receptor signaling pathway (GO:0007209), tachykinin receptor signaling pathway (GO:0007217), positive regulation of acetylcholine secretion, neurotransmission (GO:0014057), intestine smooth muscle contraction (GO:0014827), negative regulation of luteinizing hormone secretion (GO:0033685), operant conditioning (GO:0035106), positive regulation of vascular permeability (GO:0043117), positive regulation of monoatomic ion transport (GO:0043270), positive regulation of smooth muscle contraction (GO:0045987), response to electrical stimulus (GO:0051602), prolactin secretion (GO:0070459), positive regulation of uterine smooth muscle contraction (GO:0070474), positive regulation of flagellated sperm motility (GO:1902093), regulation of smooth muscle contraction (GO:0006940), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), regulation of uterine smooth muscle contraction (GO:0070472)

GO Molecular Function (4): tachykinin receptor activity (GO:0004995), substance K receptor activity (GO:0016497), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), sperm flagellum (GO:0036126), sperm head (GO:0061827), sperm midpiece (GO:0097225), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
tachykinin receptor signaling pathway	2
G protein-coupled receptor signaling pathway	2
smooth muscle contraction	2
regulation of smooth muscle contraction	2
uterine smooth muscle contraction	2
muscle system process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of neurotransmitter secretion	1
acetylcholine secretion, neurotransmission	1
regulation of acetylcholine secretion, neurotransmission	1
positive regulation of synaptic transmission, cholinergic	1
positive regulation of amine transport	1
phasic smooth muscle contraction	1
gastro-intestinal system smooth muscle contraction	1
luteinizing hormone secretion	1
negative regulation of gonadotropin secretion	1
regulation of luteinizing hormone secretion	1
learning	1
regulation of vascular permeability	1
monoatomic ion transport	1
regulation of monoatomic ion transport	1
positive regulation of transport	1
positive regulation of muscle contraction	1
response to abiotic stimulus	1
protein secretion	1
peptide hormone secretion	1
positive regulation of smooth muscle contraction	1
regulation of uterine smooth muscle contraction	1
positive regulation of cilium movement	1
flagellated sperm motility	1
regulation of flagellated sperm motility	1
positive regulation of cilium-dependent cell motility	1
positive regulation of reproductive process	1
regulation of muscle contraction	1
cell communication	1
cellular process	1
signaling	1

Protein interactions and networks

STRING

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TACR2	TAC1	P20366	998
TACR2	TAC3	Q9UHF0	998
TACR2	TAC4	Q86UU9	906
TACR2	CHKB	Q9Y259	761
TACR2	MAS1	P04201	586
TACR2	AASDHPPT	Q9NRN7	574
TACR2	TRPC7	Q9HCX4	571
TACR2	ARRB2	P32121	505
TACR2	TRPV1	Q8NER1	449
TACR2	DDX50	Q9BQ39	447
TACR2	SSTR1	P30872	443
TACR2	IGF2R	P11717	418
TACR2	VIPR2	P41587	416
TACR2	TACR1	P25103	415
TACR2	FYN	P06241	410

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TACR2	TAC1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): TACR2 (Reconstituted Complex), TACR2 (Reconstituted Complex), TACR2 (Protein-RNA), TAC1 (Reconstituted Complex), TAC3 (Reconstituted Complex)

ESM2 similar proteins: O18821, O42329, P05363, P0C0L6, P16610, P21452, P30549, P30559, P30560, P30968, P30969, P32236, P32237, P32306, P37288, P47751, P47901, P48043, P48974, P49922, P51144, P56449, P56494, P70536, P79218, P97926, Q01776, Q19PY9, Q28756, Q56H79, Q5DUB2, Q62463, Q64077, Q6W5P4, Q7T3Q7, Q868T3, Q8BZP8, Q8CH60, Q90252, Q90334

Diamond homologs: G4WMX4, O02813, O02835, O02836, O18935, O19012, O19032, O19091, O42179, O43614, O62809, O77408, O77700, O77713, O77721, O97512, P05363, P08909, P14416, P14600, P16177, P16610, P18089, P18825, P19328, P20288, P21452, P22086, P24628, P25103, P25931, P29371, P30098, P30545, P30547, P30549, P30731, P30938, P30974, P30975

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TACR2	“up-regulates activity”	GNAI1	binding
TACR2	“up-regulates activity”	GNAI3	binding
TACR2	“up-regulates activity”	GNAQ	binding
TACR2	“up-regulates activity”	GNA14	binding
“Neurokinin A”	“up-regulates activity”	TACR2	“chemical activation”
TAC1	up-regulates	TACR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

846 predictions. Top by Δscore:

Variant	Effect	Δscore
10:69407078:GCTCA:G	donor_loss	1.0000
10:69407079:CTCAC:C	donor_loss	1.0000
10:69407080:TCACC:T	donor_loss	1.0000
10:69407081:CACC:C	donor_loss	1.0000
10:69407082:ACC:A	donor_loss	1.0000
10:69407083:C:T	donor_loss	1.0000
10:69407281:C:CC	acceptor_gain	1.0000
10:69407287:C:CT	acceptor_gain	1.0000
10:69414943:A:AC	donor_gain	1.0000
10:69414944:C:CC	donor_gain	1.0000
10:69406402:ATTT:A	donor_gain	0.9900
10:69407082:A:AC	donor_gain	0.9900
10:69407083:C:CC	donor_gain	0.9900
10:69407276:ACAAA:A	acceptor_gain	0.9900
10:69407277:CAAA:C	acceptor_gain	0.9900
10:69407277:CAAAC:C	acceptor_gain	0.9900
10:69407278:AAA:A	acceptor_gain	0.9900
10:69407279:AA:A	acceptor_gain	0.9900
10:69407287:C:T	acceptor_gain	0.9900
10:69407288:A:T	acceptor_gain	0.9900
10:69408917:CCCA:C	donor_loss	0.9900
10:69408918:CCAC:C	donor_loss	0.9900
10:69408920:A:T	donor_loss	0.9900
10:69408921:C:CA	donor_loss	0.9900
10:69408921:CCTT:C	donor_gain	0.9900
10:69414959:G:A	donor_gain	0.9900
10:69415914:C:A	donor_gain	0.9900
10:69415973:CATGG:C	donor_gain	0.9900
10:69409076:CTG:C	acceptor_loss	0.9800
10:69409077:T:G	acceptor_loss	0.9800

AlphaMissense

2611 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:69407128:G:C	S298R	0.992
10:69407128:G:T	S298R	0.992
10:69407130:T:G	S298R	0.992
10:69414990:C:G	C181S	0.983
10:69414991:A:T	C181S	0.983
10:69415964:G:C	S120R	0.978
10:69415964:G:T	S120R	0.978
10:69415966:T:G	S120R	0.978
10:69416007:C:G	C106S	0.977
10:69416007:C:T	C106Y	0.977
10:69416008:A:T	C106S	0.977
10:69407245:A:C	F259L	0.976
10:69407245:A:T	F259L	0.976
10:69407247:A:G	F259L	0.976
10:69416102:A:C	N74K	0.976
10:69416102:A:T	N74K	0.976
10:69415066:A:G	W156R	0.975
10:69415066:A:T	W156R	0.975
10:69416006:G:C	C106W	0.975
10:69416029:A:G	W99R	0.973
10:69416029:A:T	W99R	0.973
10:69416027:C:A	W99C	0.972
10:69416027:C:G	W99C	0.972
10:69414991:A:G	C181R	0.971
10:69407142:A:G	W294R	0.965
10:69407142:A:T	W294R	0.965
10:69416054:G:C	N90K	0.964
10:69416054:G:T	N90K	0.964
10:69407212:G:C	F270L	0.963
10:69407212:G:T	F270L	0.963

dbSNP variants (sampled 300 via entrez): RS1000123551 (10:69415616 C>A,T), RS1000550904 (10:69417917 C>A,T), RS1000978439 (10:69411756 A>G), RS1001118367 (10:69416559 C>G,T), RS1001279450 (10:69406159 C>G), RS1001458203 (10:69407555 CA>C), RS1001530090 (10:69416811 T>C), RS1001540562 (10:69403468 T>G), RS1001792685 (10:69414283 C>T), RS1002514259 (10:69417264 T>C), RS1002514733 (10:69405881 T>C), RS1003395063 (10:69413332 C>G), RS1003424804 (10:69413427 A>G), RS1003632497 (10:69418134 G>A,C,T), RS1003894215 (10:69410983 C>T)

Disease associations

OMIM: gene MIM:162321 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2327 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

47 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,213,494 (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
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1201469	GRAMICIDIN	4
CHEMBL1221	SULCONAZOLE	4	12,121
CHEMBL1262	OXICONAZOLE	4	48
CHEMBL1289	HALOPROGIN	4	8,799
CHEMBL1479	DANAZOL	4	16,256
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL163	RITONAVIR	4	53,773
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL305660	EBASTINE	4	10,024
CHEMBL3349607	PASIREOTIDE	4	109
CHEMBL3545252	DOCETAXEL	4	1,009
CHEMBL404849	SULOCTIDIL	4	5,496
CHEMBL411	DIETHYLSTILBESTROL	4	353,912
CHEMBL428647	PACLITAXEL	4	332,542
CHEMBL496	HEXACHLOROPHENE	4	26,164
CHEMBL503	LOVASTATIN	4
CHEMBL553025	VINORELBINE	4
CHEMBL584	NELFINAVIR	4
CHEMBL633	AMIODARONE	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL71	CHLORPROMAZINE	4
CHEMBL726	FLUPHENAZINE	4
CHEMBL787	MONTELUKAST	4
CHEMBL808	ECONAZOLE	4
CHEMBL81	RALOXIFENE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Tachykinin receptors

Most potent curated ligand interactions (31 total), top 25:

Ligand	Action	Affinity	Parameter
ibodutant	Antagonist	10.3	pKi
saredutant	Antagonist	10.25	pIC50
YM44781	Antagonist	9.9	pKi
GR94800	Antagonist	9.8	pKi
[3H]saredutant	Antagonist	9.7	pKd
GR 159897	Antagonist	9.5	pKd
neuropeptide γ	Agonist	9.5	pEC50
SCH 206272	Antagonist	9.4	pKi
[Lys5,Me-Leu9,Nle10]NKA-(4-10)	Full agonist	9.4	pIC50
[125I]NKA (human, mouse, rat)	Full agonist	9.3	pKd
[3H]GR100679	Antagonist	9.2	pKd
MEN10627	Antagonist	9.2	pKi
SB 414240	Antagonist	9.0	pKi
neurokinin A	Agonist	8.89	pEC50
neuropeptide K	Agonist	8.8	pEC50
nepadutant	Antagonist	8.7	pKi
ZM-274773	Antagonist	8.62	pKi
YM44778	Antagonist	8.6	pKi
GR64349	Full agonist	8.4	pEC50
MEN 10376	Antagonist	8.1	pKi
osanetant	Antagonist	7.8	pKi
neurokinin B	Full agonist	7.7	pKi
talnetant	Antagonist	6.9	pKi
substance P	Full agonist	6.9	pKi
[Phe(Me)7]neurokinin B	Full agonist	6.9	pKi

Binding affinities (BindingDB)

120 measured of 124 human assays (137 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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-(1-hydroxycyclopropanecarbonyl)piperidine-4-carbonyl]piperidin-4-yl]-N-methyl-4-morpholin-4-ylbenzamide	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
N-[(3R,4R)-1-(1-acetylpiperidine-4-carbonyl)-3-(3,4-dichlorophenyl)piperidin-4-yl]-N-methyl-4-morpholin-4-ylbenzamide	IC50	0.42 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-bromo-N-methylbenzamide	IC50	0.45 nM	US-8470816: Nitrogen-containing heterocyclic compound and use thereof
4-[(4-chlorophenyl)methoxy]-3-ethoxybenzaldehyde	IC50	0.55 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-methoxy-N-methylbenzamide	IC50	0.56 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-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
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
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
[(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-(Adamantan-1-ylmethoxy)-3-(3,4-dichloro-phenyl)-5-(4-hydroxy-4-phenyl-piperidin-1-yl)-pentan-2-one O-methyl-oxime	KI	7 nM
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
[(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
[(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]-(3,4,5-trifluorophenyl)methanone	IC50	24 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-[2-(trifluoromethyl)-1,3-thiazol-4-yl]-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone	IC50	26 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-chloro-4-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	30 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
[(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]-(3,4,5-trifluorophenyl)methanone	IC50	30 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
(4-chlorophenyl)-[(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	31 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-(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	32 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
(4-chlorophenyl)-[(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	32 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
[(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]-(2,3,4-trifluorophenyl)methanone	IC50	33 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists
[(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]-(2,3,4,5-tetrafluorophenyl)methanone	IC50	33 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
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone	KI	33 nM
[(8R)-8-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	33 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
(3,4-dichlorophenyl)-[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	34 nM	US-9422299: Substituted [1,2,4]triazolo[4,3-a]pyrazines as selective NK-3 receptor antagonists

ChEMBL bioactivities

1033 potent at pChembl≥5 of 1110 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	Ki	0.02512	nM	CHEMBL224081
10.30	Ki	0.05012	nM	CHEMBL436981
10.30	Ki	0.05012	nM	CHEMBL1083850
10.30	Ki	0.05012	nM	CHEMBL2112922
10.28	Ki	0.05248	nM	CHEMBL243711
10.24	Ki	0.05754	nM	CHEMBL244362
10.22	Ki	0.06026	nM	CHEMBL395972
10.20	Ki	0.0631	nM	CHEMBL387506
10.20	Ki	0.0631	nM	CHEMBL439281
10.12	Ki	0.07586	nM	IBODUTANT
10.10	Ki	0.07943	nM	CHEMBL1083858
10.10	Ki	0.07943	nM	CHEMBL1083974
10.01	Ki	0.09772	nM	CHEMBL395974
10.00	Ki	0.1	nM	CHEMBL223221
10.00	Ki	0.1	nM	CHEMBL225297
10.00	Ki	0.1	nM	CHEMBL389510
10.00	Ki	0.1	nM	CHEMBL1083879
9.93	Ki	0.1175	nM	CHEMBL242626
9.90	Ki	0.1259	nM	CHEMBL224003
9.90	Ki	0.1259	nM	CHEMBL224374
9.90	Ki	0.1259	nM	CHEMBL1083869
9.90	Ki	0.1259	nM	CHEMBL1083863
9.90	Ki	0.1259	nM	CHEMBL2112925
9.89	IC50	0.13	nM	SAREDUTANT
9.88	Ki	0.1318	nM	CHEMBL394780
9.85	Ki	0.1413	nM	CHEMBL395973
9.81	Ki	0.1549	nM	CHEMBL2370064
9.81	Ki	0.1549	nM	CHEMBL59780
9.80	Ki	0.1585	nM	CHEMBL389459
9.80	Ki	0.1585	nM	CHEMBL413715
9.80	Ki	0.1585	nM	CHEMBL225588
9.80	Ki	0.1585	nM	CHEMBL266284
9.80	Ki	0.1585	nM	CHEMBL389511
9.80	Ki	0.1585	nM	CHEMBL1083875
9.80	Ki	0.1585	nM	CHEMBL1083874
9.80	Ki	0.1585	nM	CHEMBL1083873
9.80	Ki	0.1585	nM	CHEMBL1083870
9.70	Ki	0.1995	nM	CHEMBL224009
9.70	Ki	0.1995	nM	CHEMBL225392
9.70	Ki	0.1995	nM	CHEMBL389279
9.70	Ki	0.1995	nM	CHEMBL388626
9.70	Kd	0.1995	nM	CHEMBL1083850
9.70	Ki	0.2	nM	CHEMBL78284
9.66	IC50	0.22	nM	CHEMBL3642170
9.66	IC50	0.22	nM	CHEMBL3642171
9.66	IC50	0.22	nM	CHEMBL3642173
9.65	Ki	0.2239	nM	CHEMBL243496
9.64	IC50	0.23	nM	CHEMBL3642166
9.63	Ki	0.2344	nM	CHEMBL395971
9.63	Ki	0.2344	nM	CHEMBL1683146

PubChem BioAssay actives

870 with measured affinity, of 1462 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-[(1-oxothian-4-yl)amino]-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	<0.0001	uM
N-[1-[[(2R)-1-oxo-1-[[3-oxo-3-(4-pyridin-2-ylpiperazin-1-yl)propyl]amino]-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
N-[(2S)-4-(4-acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide	145472: Inhibition of cloned human NK2 (Neurokinin 2) receptor, stably expressed in chinese hamster ovary (CHO) cells was determined	ic50	0.0001	uM
(2S,5S,8R)-5-benzyl-8-[(3,4-dichlorophenyl)methyl]-2-(1H-indol-3-ylmethyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	211887: Inhibitory affinity constant (pKi) against tachykinin receptor 2 (NK-2R) using heterologous competition experiments	ki	0.0001	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-(thian-4-ylamino)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
N-[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]-2-(4-sulfamoylpiperazin-1-yl)acetamide	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-(oxan-4-ylamino)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
(2S,5S,8R,12R)-12-(4-acetylpiperazin-1-yl)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
6-methyl-N-[1-[[(2S)-5-[4-(oxan-4-ylmethyl)piperazin-1-yl]-1-phenylpentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0001	uM
6-methyl-N-[1-[[(2S)-5-[4-(oxane-4-carbonyl)piperazin-1-yl]-1-phenylpentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0001	uM
6-methyl-N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
6-bromo-N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
N-[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]-2-(4-hydroxypiperidin-1-yl)acetamide	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
6-chloro-N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
N-[1-[[(2R)-1-oxo-3-phenyl-1-[3-(4-sulfamoylpiperazin-1-yl)propylamino]propan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-6-(trifluoromethyl)-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
6-methoxy-N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
6-(diethylamino)-N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0001	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-[(1-methylsulfonylpiperidin-4-yl)amino]-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
4-[[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]amino]piperidine-1-sulfonamide	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0001	uM
6-methyl-N-[1-[[(2S)-5-[1-(oxan-4-ylmethyl)piperidin-4-yl]-1-phenylpentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0001	uM
N-[1-[[(2S)-5-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]-1-phenylpentan-2-yl]carbamoyl]cyclopentyl]-6-methyl-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0001	uM
(4S)-4-amino-1-[4-(oxan-4-ylmethyl)piperazin-1-yl]-5-phenylpentan-1-one;hydrochloride	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0001	uM
6-methyl-N-[1-[[(2R)-4-[4-(oxan-4-yl)piperazin-1-yl]-1-phenylbutan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0001	uM
(2S,5S,8S)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-(4-piperidin-1-ylpiperidine-1-carbonyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	211892: Displacement of [125I]NKA from human Tachykinin receptor 2 expressed in CHO cells	ki	0.0001	uM
(2S,5S,8S)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-(morpholine-4-carbonyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	211892: Displacement of [125I]NKA from human Tachykinin receptor 2 expressed in CHO cells	ki	0.0001	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-morpholin-4-yl-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	211887: Inhibitory affinity constant (pKi) against tachykinin receptor 2 (NK-2R) using heterologous competition experiments	ki	0.0002	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-(4-piperidin-1-ylpiperidin-1-yl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-[methyl(oxan-4-yl)amino]-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
(2S,5S,8R,12R)-12-amino-5-benzyl-8-[(3,4-dichlorophenyl)methyl]-2-(1H-indol-3-ylmethyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-(4-morpholin-4-ylpiperidin-1-yl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
(2S,5S,8R,12S)-12-amino-5-benzyl-8-[(3,4-dichlorophenyl)methyl]-2-(1H-indol-3-ylmethyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
(2S,5S,8R,12R)-5,8-dibenzyl-12-[(1,1-dioxothian-4-yl)amino]-2-(1H-indol-3-ylmethyl)-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0002	uM
6-fluoro-N-[1-[[(2R)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0002	uM
(2S)-N-[(2S)-1-amino-1-oxohexan-2-yl]-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-benzamidopropanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide	145818: Binding affinity against human NK2 receptors expressed in CHO cells using [3H]GR-100679 as radioligand	ki	0.0002	uM
(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-12-[(1-methylpiperidin-4-yl)amino]-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
6-methyl-N-[1-[[(2S)-1-phenyl-5-[4-(pyridin-2-ylmethyl)piperazin-1-yl]pentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0002	uM
6-methyl-N-[1-[[(2S)-1-phenyl-5-[4-(thiophen-2-ylmethyl)piperazin-1-yl]pentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0002	uM
6-methyl-N-[1-[[(2S)-1-phenyl-5-[4-(thiophen-3-ylmethyl)piperazin-1-yl]pentan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0002	uM
N-[1-[[(2S)-5-[4-(furan-3-ylmethyl)piperazin-1-yl]-1-phenylpentan-2-yl]carbamoyl]cyclopentyl]-6-methyl-1-benzothiophene-2-carboxamide	482717: Displacement of [3H]neurokinin A from human NK2 receptor	ki	0.0002	uM
N-[1-[[(2S)-1-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-4-pyrrol-1-ylbenzamide	579760: Displacement of [125I]neurokinin A from human NK2 receptor after 30 mins	ki	0.0002	uM
(2S)-N-[(2S)-1-amino-1-oxohexan-2-yl]-1-[(2R)-1-[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-benzamidopropanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide	1181861: Displacement of [3H]GR100679 from NK2 receptor (unknown origin) expressed in CHO/T cells	ki	0.0002	uM
N-[(2Z,3R)-5-[4-[3-(2-amino-2-oxoethyl)-2-oxo-1,3-diazinan-1-yl]piperidin-1-yl]-3-(3,4-dichlorophenyl)-2-methoxyiminopentyl]-3,5-dichloro-N-methylbenzamide	211720: Binding affinity against recombinant human tachykinin receptor 2 in CHO cells using [3H]-NKA as radioligand	ki	0.0002	uM
N-[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]-2-(4-morpholin-4-ylpiperidin-1-yl)acetamide	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0002	uM
6-chloro-N-[1-[[(2R)-1-(3-morpholin-4-ylpropylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]cyclopentyl]-1-benzothiophene-2-carboxamide	298231: Displacement of [125I]neurokinin A from human recombinant NK2 receptor	ki	0.0003	uM
N-[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]-2-morpholin-4-ylacetamide	211887: Inhibitory affinity constant (pKi) against tachykinin receptor 2 (NK-2R) using heterologous competition experiments	ki	0.0003	uM
(2S,5S,8R,12R)-5-benzyl-8-[(3,4-dichlorophenyl)methyl]-2-(1H-indol-3-ylmethyl)-12-morpholin-4-yl-1,4,7,10-tetrazacyclotetradecane-3,6,11,14-tetrone	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0003	uM
N-[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]acetamide	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0003	uM
N-[(2S,5S,8R,12R)-5,8-dibenzyl-2-(1H-indol-3-ylmethyl)-3,6,11,14-tetraoxo-1,4,7,10-tetrazacyclotetradec-12-yl]-2-(1-oxo-1,4-thiazinan-4-yl)acetamide	282615: Displacement of [125I]neurokinin A from human NK2 receptor expressed in CHOK1 cells	ki	0.0003	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
terbufos	increases methylation	1
SR 48968	affects binding	1
CGP 52608	increases reaction, affects binding	1
MEN 11420	affects binding	1
SR 144190	affects binding, decreases activity	1
(N-N’-bis-(2-(1H-indol-3-yl)-ethyl)-N,N’-bis-(3-thiomorpholin-4-yl-propyl)-phthalamide)	affects binding, decreases activity	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Capsaicin	increases response to substance	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Neurokinin A	affects binding	1

ChEMBL screening assays

338 unique, capped per target: 319 binding, 18 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000187	Binding	Binding affinity to NK2 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1120424	Functional	Antagonist activity at NK2 receptor in human urinary bladder assessed as inhibition of [beta-Ala8]NKA(4-10)-induced tissue contractions	Structure-activity relationships of 6-methyl-benzo[b]thiophene-2-carboxylic acid (1-[(S)-1-benzyl-4-[4-(tetrahydropyran-4-ylmethyl)piperazin-1-yl]butylcarbamoyl]cyclopentyl)amide, potent antagonist of the neurokinin-2 receptor. — J Med Chem
CHEMBL4687886	ADMET	Displacement of [125I]NKA from recombinant human NK2 receptor at 10 uM incubated for 60 mins by radiometric scintillation analysis relative to control	Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family. — Bioorg Med Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_H471	CHO-K1/NK2	Spontaneously immortalized cell line	Female
CVCL_KZ18	PathHunter CHO-K1 TACR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB36	PathHunter U2OS TACR2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_YK59	U2OS TACR2 HiTSeeker	Cancer cell line	Female
CVCL_YK71	U2OS MPX-Nomad NK2R	Cancer cell line	Female
CVCL_ZK89	GeneBLAzer TACR2-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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