TACR3

Summary

TACR3 (tachykinin receptor 3, HGNC:11528) is a protein-coding gene on chromosome 4q24, encoding Neuromedin-K receptor (P29371). Receptor for the tachykinin neuromedin-K (neurokinin B), also able to bind and respond to tachynins substance K/neurokinin A and substance P.

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 neurokinin 3, also referred to as neurokinin B.

Source: NCBI Gene 6870 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypogonadotropic hypogonadism 11 with or without anosmia (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 174 total — 9 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 78
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11528
Approved symbol	TACR3
Name	tachykinin receptor 3
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	NK3R, NKR, TAC3R
Ensembl gene	ENSG00000169836
Ensembl biotype	protein_coding
OMIM	162332
Entrez	6870

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000304883

RefSeq mRNA: 1 — MANE Select: NM_001059 NM_001059

CCDS: CCDS3664

Canonical transcript exons

ENST00000304883 — 5 exons

Exon	Start	End
ENSE00001131476	103586031	103589994
ENSE00001134536	103591487	103591683
ENSE00001134546	103656194	103656344
ENSE00001278370	103658215	103658403
ENSE00001278392	103719128	103719985

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 63.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1378 / max 16.2065, expressed in 61 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53448	0.1378	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	63.88	gold quality
secondary oocyte	CL:0000655	58.51	gold quality
hypothalamus	UBERON:0001898	56.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	51.75	gold quality
prefrontal cortex	UBERON:0000451	51.25	gold quality
spinal cord	UBERON:0002240	50.67	gold quality
amygdala	UBERON:0001876	50.28	gold quality
urinary bladder	UBERON:0001255	49.82	gold quality
skin of hip	UBERON:0001554	49.77	silver quality
stromal cell of endometrium	CL:0002255	48.81	gold quality
substantia nigra	UBERON:0002038	48.80	gold quality
midbrain	UBERON:0001891	47.71	gold quality
ventricular zone	UBERON:0003053	47.54	gold quality
corpus callosum	UBERON:0002336	46.13	silver quality
temporal lobe	UBERON:0001871	45.54	gold quality
colonic epithelium	UBERON:0000397	44.90	gold quality
frontal cortex	UBERON:0001870	44.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	44.09	gold quality
primary visual cortex	UBERON:0002436	43.57	silver quality
neocortex	UBERON:0001950	43.50	gold quality
Ammon’s horn	UBERON:0001954	43.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
oocyte	CL:0000023	43.34	gold quality
epithelium of nasopharynx	UBERON:0001951	42.96	gold quality
islet of Langerhans	UBERON:0000006	42.80	silver quality
skeletal muscle tissue	UBERON:0001134	42.67	gold quality
cerebral cortex	UBERON:0000956	42.56	gold quality
vastus lateralis	UBERON:0001379	41.75	gold quality
quadriceps femoris	UBERON:0001377	41.70	gold quality
heart right ventricle	UBERON:0002080	41.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting TACR3, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-4515	95.70	65.73	716

Literature-anchored findings (GeneRIF, showing 32)

• 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)
• Results found no significant difference in the expression of tachykinins receptors between pre-eclamptic placenta and normal controls. (PMID:16709596)
• 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)
• Our results suggest that TACR3 is unlikely to be related to the development of schizophrenia in the Japanese population. (PMID:18287949)
• small nucleotide polymorphisms in the 3’ region of tachykinin receptor 3 gene (TACR3) provided significant evidence of association with alcohol dependence (PMID:18422838)
• In healthy human colon a higher expression level of the TACR2 mRNA alpha isoform, the gene encoding the functional tachykinin NK(2) receptor, was observed in comparison to TACR1 and TACR3 mRNAs genes encoding for NK(1) and NK(3) receptors respectively (PMID:18835556)
• TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. (PMID:19079066)
• Homozygosity for the TACR3 His148Leu mutation leads to failure of sexual maturation in humans, whereas signaling by the mutant receptor in vitro in response to either NKB or senktide is severely impaired. (PMID:19755480)
• NK-3R plays a crucial role in hypothalamic gonadotropin releasing hormone release in humans. (PMID:20194706)
• broad cohort of normosmic hypogonadotropic hypogonadism probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships (PMID:20332248)
• report of a Japanese female with hypogonadism(IHH) and compound heterozygous TACR3 mutations and her heterozygous parents; results suggest hypothalamic dysfunction as primary cause for IHH in patients with biallelic TACR3 mutations (PMID:20395662)
• The gonadotropin axis dysfunction associated with nCHH due to TAC3/TACR3 mutations is related to a low GnRH pulsatile frequency leading to a low frequency of alpha-subunit pulses and to an elevated FSH/LH ratio. (PMID:22031817)
• NKB/NK(3)R and kisspeptin/KISS1R are present in female peripheral reproductive tissues with colocalization of both systems in some non-neuronal cell populations of the human female genital tract. (PMID:22424618)
• Data suggest that mutations in TACR3 and GNRHR are the most common causative mutations in normosmic idiopathic hypogonadotropic hypogonadism in families in Turkey. (PMID:22766261)
• Sex differences in the neurokinin B system in the human infundibular nucleus. (PMID:23019350)
• Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders and loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. (PMID:23329188)
• Expression of the gene encoding TACR3 is significantly up-regulated in leiomyomas, compared with matched myometrium. (PMID:23656837)
• the rs2765 SNP predicted the degree of impairment of learning and memory in 209 elderly patients with cognitive impairments (PMID:23983264)
• Studies indicate the molecular mechanisms by which NK3R mutations cause GnRH deficiency. (PMID:24376026)
• data indicate that GPR54 and TACR3 gene mutations are not a frequent cause of ICPP. The identified A/G synonymous SNP (dbSNP ID: rs10407968) located in exon 1 of the gene is not likely to have a pathogenic role in exon splicing (PMID:24434351)
• mutations in TAC and TACR3 are not a common cause for ICPP. (PMID:24802197)
• None of the 4 single polymorphisms studied in TACR3 are linked directly to puberty onset time, but A63P in TAC3 is statistically associated with precocious puberty. (PMID:25153567)
• Elevated CRP is likely a pathogenic factor contributing to preeclampsia by binding to phosphocholinated neurokinin B and preferentially activating NK3R. (PMID:25452470)
• observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain; in the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined (PMID:26993630)
• Neuropeptide derivatives to regulate the reproductive axis: Kisspeptin receptor (KISS1R) ligands and neurokinin-3 receptor (NK3R) ligands. (PMID:27271543)
• reduced to an almost undetectable level in polycystic ovary syndrome granulosa cells (PMID:27580802)
• results suggest that peripheral sensory nerve-derived TAC3 may affect gingival oral squamous cell carcinoma cells through TACR3 in the bone matrix (PMID:27919954)
• Three Single-nucleotide polymorphisms (on chromosomes 3 and 11) were associated with vasomotor menopause symptoms in the African American group. However, 14 Single-nucleotide polymorphisms, all located on chromosome 4 in the tachykinin receptor 3 (TACR3) locus, had similar effect sizes across studies/participants’ ancestry. Genetic variation in TACR3 may contribute to the risk of vasomotor menopause symptoms. (PMID:28231077)
• High NK-3R expression is associated with Oral Squamous Cell Carcinoma. (PMID:29061792)
• Identified a newly discovered stopgain mutation in tachykinin receptor 3 (TACR3) in nonobstructive azoospermia paitents. (PMID:30390321)
• Neurokinin receptors in drug and alcohol addiction. (PMID:32067964)
• The overexpression of neurokinin B-neurokinin 3 receptor system exerts direct effects on the ovary under PCOS-like conditions to interfere with mitochondrial function. (PMID:36453600)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tacr3l	ENSDARG00000003054
danio_rerio	tacr3a	ENSDARG00000075112
mus_musculus	Tacr3	ENSMUSG00000028172
rattus_norvegicus	Tacr3	ENSRNOG00000009372
caenorhabditis_elegans		WBGENE00006576

Paralogs (33): TACR2 (ENSG00000075073), 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), 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

Neuromedin-K receptor — P29371 (reviewed: P29371)

Alternative names: NK-3 receptor, Neurokinin B receptor, Tachykinin receptor 3

All UniProt accessions (1): P29371

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the tachykinin neuromedin-K (neurokinin B), also able to bind and respond to tachynins substance K/neurokinin A and substance P. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K and substance P. Neuromedin-K binding to its receptor triggers G protein-coupled receptor signaling via activation of G(q) and phosphatidylinositol hydrolysis by phospholipase C. Neuromedin-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.

Post-translational modifications. The anchoring of this receptor to the plasma membrane is probably mediated by the palmitoylation of a cysteine residue.

Disease relevance. Hypogonadotropic hypogonadism 11 with or without anosmia (HH11) [MIM:614840] A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in TACR3 as well as in other HH-associated genes including FGFR1, SPRY4 and KAL1.

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

RefSeq proteins (1): NP_001050* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001013	NK3_rcpt	Family
IPR001681	Neurokn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (67 total): helix 17, mutagenesis site 9, topological domain 8, transmembrane region 7, sequence variant 7, turn 6, glycosylation site 3, sequence conflict 3, strand 2, chain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8JBG	ELECTRON MICROSCOPY	2.8
8JBH	ELECTRON MICROSCOPY	2.9
8JBF	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29371-F1	74.14	0.43

Antibody-complex structures (SAbDab): 3 — 8JBF, 8JBG, 8JBH

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): 374

Disulfide bonds (1): 158–233

Glycosylation sites (3): 23, 50, 73

Mutagenesis-validated functional residues (9):

Position	Phenotype
78	decreased sensitivity to activation by nkb.
78	loss of activation by nkb.
138	loss of activation by nkb.
142	decreased sensitivity to activation by nkb.
166	decreased sensitivity to activation by nkb.
232	no effect on activation by nkb.
315	decreased sensitivity to activation by nkb.
319	decreased sensitivity to activation by nkb.
338	loss of activation by nkb.

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: 351 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_4HR_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_RESPONSE_TO_ESTRADIOL, chr4q24, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_COCAINE, GOBP_ASSOCIATIVE_LEARNING, MODULE_64, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION

GO Biological Process (17): 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 heart rate (GO:0010460), response to estradiol (GO:0032355), positive regulation of luteinizing hormone secretion (GO:0033686), regulation of dopamine metabolic process (GO:0042053), response to cocaine (GO:0042220), drinking behavior (GO:0042756), positive regulation of blood pressure (GO:0045777), vagina development (GO:0060068), regulation of feeding behavior (GO:0060259), positive regulation of uterine smooth muscle contraction (GO:0070474), positive regulation of flagellated sperm motility (GO:1902093), conditioned place preference (GO:1990708), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): tachykinin receptor activity (GO:0004995), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), dendritic spine membrane (GO:0032591), neuronal cell body membrane (GO:0032809), axon terminus (GO:0043679), dendritic spine head (GO:0044327), sperm midpiece (GO:0097225), membrane (GO:0016020), dendrite membrane (GO:0032590), neuronal cell body (GO:0043025)

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
response to oxygen-containing compound	2
feeding behavior	2
neuron projection membrane	2
dendritic spine	2
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
regulation of heart rate	1
positive regulation of heart contraction	1
response to lipid	1
luteinizing hormone secretion	1
positive regulation of gonadotropin secretion	1
regulation of luteinizing hormone secretion	1
regulation of catecholamine metabolic process	1
dopamine metabolic process	1
response to alkaloid	1
regulation of blood pressure	1
female genitalia development	1
regulation of behavior	1
positive regulation of smooth muscle contraction	1
uterine 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
associative learning	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
neuropeptide receptor activity	1
transmembrane signaling receptor activity	1

Protein interactions and networks

STRING

868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TACR3	TAC3	Q9UHF0	999
TACR3	TAC1	P20366	991
TACR3	KISS1	Q15726	958
TACR3	GNRH1	P01148	905
TACR3	TAC4	Q86UU9	896
TACR3	NSMF	Q6X4W1	887
TACR3	PROK2	Q9HC23	856
TACR3	CHD7	Q9P2D1	811
TACR3	CHKB	Q9Y259	732
TACR3	PDYN	P01213	728
TACR3	ANOS1	P23352	718
TACR3	GNRH2	O43555	685
TACR3	FGFR1	P11362	678
TACR3	HS6ST1	O60243	667
TACR3	SEMA3A	Q14563	630

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TACR3	C6orf47	psi-mi:“MI:0914”(association)	0.530
TACR3	TAC3	psi-mi:“MI:0915”(physical association)	0.400
TACR3	TCAF2	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): TACR3 (Reconstituted Complex), TVP23C (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATL2 (Affinity Capture-MS), THNSL1 (Affinity Capture-MS), ABCB8 (Affinity Capture-MS), PKP4 (Affinity Capture-MS), C6orf47 (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), PBXIP1 (Affinity Capture-MS), MAP2K7 (Affinity Capture-MS), FARP2 (Affinity Capture-MS)

ESM2 similar proteins: O08786, O62709, O97512, O97772, P05363, P14600, P16177, P21451, P21452, P25103, P26684, P28088, P29371, P30098, P30547, P30548, P30551, P30559, P30560, P30872, P30873, P30975, P32238, P32306, P35463, P37288, P47937, P48043, P48302, P56449, P56494, P70031, P70536, P79218, P97926, Q28756, Q49LX5, Q5D0K2, Q5DUB1, Q5DUB2

Diamond homologs: A1ZAX0, B1PHQ8, B9VR26, E7F7V7, F1MV99, F1R332, O02836, O08726, O08858, O35786, O43603, O43613, O60755, O88626, O88853, O88854, O97512, O97661, O97666, P0C7U5, P16177, P21109, P25103, P28646, P29371, P30098, P30547, P30680, P30872, P30873, P30874, P30875, P30935, P30936, P30937, P30938, P30974, P30975, P31391, P32250

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
TACR3	“up-regulates activity”	GNAS	binding
TACR3	“up-regulates activity”	GNAL	binding
TACR3	“up-regulates activity”	GNAI1	binding
TACR3	“up-regulates activity”	GNAI3	binding
TACR3	“up-regulates activity”	GNAQ	binding
TACR3	“up-regulates activity”	GNA14	binding
TACR3	“up-regulates activity”	GNA12	binding
TACR3	“up-regulates activity”	GNA13	binding
“Neurokinin B”	“up-regulates activity”	TACR3	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	8
Uncertain significance	90
Likely benign	41
Benign	12

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
14025	NM_001059.3(TACR3):c.278G>A (p.Gly93Asp)	Pathogenic
1691567	NM_001059.3(TACR3):c.370del (p.Leu124_Val125insTer)	Pathogenic
2424810	NC_000004.11:g.(?101947022)(106061534_?)del	Pathogenic
3248549	NM_001059.3(TACR3):c.1003C>T (p.Gln335Ter)	Pathogenic
373350	NM_001059.3(TACR3):c.548+2T>C	Pathogenic
4281244	NM_001059.3(TACR3):c.992G>A (p.Trp331Ter)	Pathogenic
4849262	NM_001059.3(TACR3):c.19del (p.Ala7fs)	Pathogenic
66084	NM_001059.3(TACR3):c.824G>A (p.Trp275Ter)	Pathogenic
66085	NM_001059.3(TACR3):c.766T>C (p.Tyr256His)	Pathogenic
180148	NM_001059.3(TACR3):c.511G>C (p.Ala171Pro)	Likely pathogenic
180159	NM_001059.3(TACR3):c.623G>A (p.Trp208Ter)	Likely pathogenic
183684	NM_001059.3(TACR3):c.692C>T (p.Thr231Ile)	Likely pathogenic
2631123	NM_001059.3(TACR3):c.737+1G>C	Likely pathogenic
2633867	NM_001059.3(TACR3):c.311_312insTCCTGGATTGCAAGTATGAAATCTTCCTGGATTTGGGAAATCT (p.Leu104_Ile105insProGlyLeuGlnValTer)	Likely pathogenic
2964605	NM_001059.3(TACR3):c.1090C>T (p.Arg364Ter)	Likely pathogenic
3896750	NM_001059.3(TACR3):c.247_267del (p.Trp83_Ser89del)	Likely pathogenic
817809	NM_001059.3(TACR3):c.447_448del (p.Ser149fs)	Likely pathogenic

SpliceAI

646 predictions. Top by Δscore:

Variant	Effect	Δscore
4:103589753:T:TA	donor_gain	1.0000
4:103591680:CAAC:C	acceptor_gain	1.0000
4:103591683:CCTA:C	acceptor_loss	1.0000
4:103591684:CTAT:C	acceptor_loss	1.0000
4:103658213:A:AC	donor_gain	1.0000
4:103658214:C:CC	donor_gain	1.0000
4:103658337:T:TA	donor_gain	1.0000
4:103589990:GAAAT:G	acceptor_gain	0.9900
4:103589992:AATCT:A	acceptor_loss	0.9900
4:103589993:AT:A	acceptor_gain	0.9900
4:103589995:C:CC	acceptor_gain	0.9900
4:103589995:CTG:C	acceptor_loss	0.9900
4:103589996:T:C	acceptor_loss	0.9900
4:103590006:C:CT	acceptor_gain	0.9900
4:103590007:A:T	acceptor_gain	0.9900
4:103590011:C:CT	acceptor_gain	0.9900
4:103591481:TTTTA:T	donor_loss	0.9900
4:103591482:TTTA:T	donor_loss	0.9900
4:103591483:TTACC:T	donor_loss	0.9900
4:103591484:TAC:T	donor_loss	0.9900
4:103591485:A:T	donor_loss	0.9900
4:103591486:C:G	donor_loss	0.9900
4:103591684:C:CC	acceptor_gain	0.9900
4:103591685:T:A	acceptor_loss	0.9900
4:103656345:C:CC	acceptor_gain	0.9900
4:103656347:A:C	acceptor_gain	0.9900
4:103658208:AACTT:A	donor_loss	0.9900
4:103658209:A:C	donor_gain	0.9900
4:103658209:ACTT:A	donor_loss	0.9900
4:103658210:CTT:C	donor_loss	0.9900

AlphaMissense

3049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:103591531:G:C	S347R	0.999
4:103591531:G:T	S347R	0.999
4:103591533:T:G	S347R	0.999
4:103591648:A:C	F308L	0.999
4:103591648:A:T	F308L	0.999
4:103591650:A:G	F308L	0.999
4:103658241:C:A	W237C	0.999
4:103658241:C:G	W237C	0.999
4:103658330:A:G	W208R	0.999
4:103658330:A:T	W208R	0.999
4:103719128:C:A	R183M	0.999
4:103589991:A:C	F363L	0.998
4:103589991:A:T	F363L	0.998
4:103589993:A:G	F363L	0.998
4:103591631:G:C	P314R	0.998
4:103591634:A:G	L313P	0.998
4:103591641:A:G	C311R	0.998
4:103656306:G:C	P259R	0.998
4:103658253:G:C	C233W	0.998
4:103658254:C:G	C233S	0.998
4:103658255:A:G	C233R	0.998
4:103658255:A:T	C233S	0.998
4:103719160:G:C	S172R	0.998
4:103719160:G:T	S172R	0.998
4:103719162:T:G	S172R	0.998
4:103719223:C:A	W151C	0.998
4:103719223:C:G	W151C	0.998
4:103719225:A:G	W151R	0.998
4:103719225:A:T	W151R	0.998
4:103719296:A:G	L127P	0.998

dbSNP variants (sampled 300 via entrez): RS1000021853 (4:103705078 C>G), RS1000024577 (4:103665253 G>A), RS1000029300 (4:103641376 G>A), RS1000045129 (4:103628511 C>A), RS10000527 (4:103601776 C>T), RS1000068055 (4:103623400 A>G), RS1000077983 (4:103623139 T>C), RS1000107521 (4:103653951 C>A,T), RS1000109735 (4:103703675 T>C), RS1000136925 (4:103628434 C>A,T), RS1000139051 (4:103600168 C>T), RS1000156342 (4:103667091 C>T), RS1000191051 (4:103688931 T>A), RS1000191989 (4:103599983 G>A), RS1000195950 (4:103612351 C>T)

Disease associations

OMIM: gene MIM:162332 | disease phenotypes: MIM:614840, MIM:146110, MIM:147950

GenCC curated gene-disease

Disease	Classification	Inheritance
hypogonadotropic hypogonadism 11 with or without anosmia	Strong	Autosomal recessive
hypogonadotropic hypogonadism	Supportive	Autosomal dominant
Kallmann syndrome	Supportive	Autosomal dominant

Mondo (6): hypogonadotropic hypogonadism 11 with or without anosmia (MONDO:0013913), amenorrhea (MONDO:0001836), hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), autism spectrum disorder (MONDO:0005258), hypogonadotropic hypogonadism (MONDO:0018555), Kallmann syndrome (MONDO:0018800)

Orphanet (3): Kallmann syndrome (Orphanet:478), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000002	Abnormality of body height
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000013	Hypoplasia of the uterus
HP:0000026	Male hypogonadism
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000104	Renal agenesis
HP:0000118	Phenotypic abnormality
HP:0000134	Female hypogonadism
HP:0000144	Decreased fertility
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000316	Hypertelorism
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000551	Color vision defect
HP:0000639	Nystagmus
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000789	Infertility
HP:0000802	Impotence
HP:0000823	Delayed puberty
HP:0000830	Anterior hypopituitarism

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002541_11	Menarche (age at onset)	5.000000e-13
GCST003993_10	Menarche (age at onset)	3.000000e-08
GCST005790_93	Rosacea symptom severity	6.000000e-06
GCST006979_148	Heel bone mineral density	1.000000e-10
GCST007576_318	Chronotype	1.000000e-08
GCST008181_18	Spontaneous preterm birth without premature rupture of membranes	6.000000e-06
GCST008839_389	Height	5.000000e-12
GCST012227_1290	Hip circumference adjusted for BMI	2.000000e-09
GCST012227_1291	Hip circumference adjusted for BMI	2.000000e-13
GCST012229_81	Hip index	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0009180	rosacea severity measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0006917	spontaneous preterm birth
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
C562785	Idiopathic Hypogonadotropic Hypogonadism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4429 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 63,308 (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
CHEMBL1471	APREPITANT	4	901
CHEMBL3608680	FEZOLINETANT	4	116
CHEMBL447955	SERLOPITANT	3	295
CHEMBL10188	TALNETANT	2	3,273
CHEMBL346178	OSANETANT	2	2,277
CHEMBL3545233	PAVINETANT	2	73
CHEMBL373569	ELEDOISIN	2	1,297
CHEMBL9960	AZD-7624	2	69
CHEMBL235363	SUBSTANCE P	1	55,007

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1384401	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1384401	TACR3	3	2.00	1	opioids

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
osanetant	Antagonist	9.96	pKi
[3H]osanetant	Antagonist	9.9	pKd
SSR 146977	Antagonist	9.6	pKi
SCH 206272	Antagonist	9.5	pKi
senktide	Agonist	9.3	pEC50
neurokinin B	Full agonist	9.2	pKi
hemokinin 1	Full agonist	9.1	pKi
talnetant	Antagonist	9.0	pKi
[Phe(Me)7]neurokinin B	Full agonist	8.9	pEC50
SB 235375	Antagonist	8.7	pKi
[3H]senktide	Full agonist	8.7	pKd
pavinetant	Antagonist	8.7	pKi
FK 224	Antagonist	8.4	pKi
N′,2-diphenylquinoline-4-carbohydrazide	Antagonist	8.4	pIC50
N’,2-diphenylquinoline-4-carbohydrazide 8m	Antagonist	8.4	pIC50
PD 161182	Antagonist	8.15	pIC50
GSK 172981	Antagonist	8.11	pKi
GSK 256471	Antagonist	8.08	pKi
SB 218795	Antagonist	7.97	pKi
PD157672	Antagonist	7.9	pIC50
SB 222200	Antagonist	7.7	pIC50
fezolinetant	Antagonist	7.6	pKi
[Trp7, β-Ala8] neurokinin A-(4-10)	Antagonist	7.46	pA2
kassinin	Full agonist	7.0	pIC50
eledoisin	Full agonist	6.6	pIC50

Binding affinities (BindingDB)

307 measured of 314 human assays (321 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(6-cyano-3-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.3 nM	US-9346786: Pyrrolidine compounds
SCH 206272	KI	0.3 nM
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-acetyl-2-pyridinyl)piperidine-4-carbonyl]-4-(4-chloro-3-fluorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.5 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-chloro-2-pyridinyl)piperidine-4-carbonyl]-4-(3,4-dichlorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.5 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-acetyl-2-pyridinyl)piperidine-4-carbonyl]-4-(3,4-dichlorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.5 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-chloro-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.6 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-cyano-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.7 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(6-cyanopyridazin-3-yl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.7 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-methylsulfonyl-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.7 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-cyanopyrazin-2-yl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.8 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(3,4-dichlorophenyl)-1-[1-(5-fluoro-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.8 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-carbamoyl-2-pyridinyl)piperidine-4-carbonyl]-4-(3,4-dichlorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	0.9 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(3,4-dichlorophenyl)-1-[1-(1-methylcyclopropanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	1 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-fluoro-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	1 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(3,3-difluorocyclobutanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	1 nM	US-9346786: Pyrrolidine compounds
SB-2234	KI	1 nM
(4-fluorophenyl) N-[(3S,4R)-4-(3,4-dichlorophenyl)-1-[1-[5-(trifluoromethyl)-2-pyridinyl]piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	1.6 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) 2-[(3R,4R)-1-[1-(5-carbamoyl-2-pyridinyl)piperidine-4-carbonyl]-4-(4-chloro-3-fluorophenyl)pyrrolidin-3-yl]butanoate	KI	1.7 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-acetyl-2-pyridinyl)piperidine-4-carbonyl]-4-(3-chloro-4-fluorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	1.7 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(3-chloro-4-fluorophenyl)-1-[1-(5-chloro-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	1.8 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(5-methylsulfonyl-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(5-cyanopyrazin-2-yl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(6-cyanopyridazin-3-yl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(5-cyano-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-[5-(trifluoromethyl)-2-pyridinyl]piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(1-methylcyclopropanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-methyl-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-cyano-2-pyridinyl)piperidine-4-carbonyl]-4-(3,4-difluorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-[1-(6-cyano-3-pyridinyl)piperidine-4-carbonyl]-4-(3,4-difluorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(cyclobutanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-[1-(trifluoromethyl)cyclobutanecarbonyl]piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(3-fluorocyclobutanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(1-cyanocyclopropanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-1-(1-acetylpiperidine-4-carbonyl)-4-(4-chloro-3-fluorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	2 nM	US-9346786: Pyrrolidine compounds
[(8R)-8-methyl-3-(2-propan-2-yl-1,3-oxazol-4-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-(4-thiophen-2-ylphenyl)methanone	IC50	2 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)-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]-(4-thiophen-2-ylphenyl)methanone	IC50	2 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
(4-fluorophenyl) N-[(3R,4S)-4-(4-chlorophenyl)-1-[1-(5-cyano-2-pyridinyl)piperidine-4-carbonyl]-3-methylpyrrolidin-3-yl]-N-methylcarbamate	KI	2.1 nM	US-8618303: Pyrrolidine derivatives
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(cyclobutanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2.1 nM	US-9346786: Pyrrolidine compounds
4-[4-[(3R,4R)-4-(4-chlorophenyl)-3-[(5-chloro-2-pyridinyl)oxymethyl]-3-methylpyrrolidine-1-carbonyl]piperidin-1-yl]benzonitrile	KI	2.3 nM	US-8507535: Methyl-pyrrolidine ether derivatives
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(3,3-difluorocyclobutanecarbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	2.4 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3R,4S)-4-(4-chlorophenyl)-1-[1-(6-cyano-3-pyridinyl)piperidine-4-carbonyl]-3-methylpyrrolidin-3-yl]-N-methylcarbamate	KI	2.8 nM	US-8618303: Pyrrolidine derivatives
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-(5-cyano-2-pyridinyl)piperidine-4-carbonyl]-4-methylpyrrolidin-3-yl]-N-methylcarbamate	KI	2.9 nM	US-8618303: Pyrrolidine derivatives
(4-fluorophenyl) N-[(3S,4R)-1-[1-(5-acetyl-2-pyridinyl)piperidine-4-carbonyl]-4-(4-chlorophenyl)pyrrolidin-3-yl]-N-ethylcarbamate	KI	3 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chlorophenyl)-1-[1-[5-(trifluoromethyl)-2-pyridinyl]piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	3 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(4-cyano-2-pyridinyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	3 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(3-methyloxetane-3-carbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	3 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(2,2-dimethyloxane-4-carbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	3 nM	US-9346786: Pyrrolidine compounds
(4-fluorophenyl) N-[(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-[1-(5-fluoropyridine-2-carbonyl)piperidine-4-carbonyl]pyrrolidin-3-yl]-N-ethylcarbamate	KI	3 nM	US-9346786: Pyrrolidine compounds
[(8R)-3-(2-ethyl-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	3 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-(2-ethenyl-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	3 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

ChEMBL bioactivities

1919 potent at pChembl≥5 of 1931 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.96	EC50	0.011	nM	CHEMBL3736177
10.92	EC50	0.012	nM	CHEMBL2347491
10.92	EC50	0.012	nM	CHEMBL3735159
10.89	EC50	0.013	nM	CHEMBL583102
10.89	EC50	0.013	nM	CHEMBL3735427
10.85	EC50	0.014	nM	CHEMBL3736361
10.77	EC50	0.017	nM	CHEMBL2347513
10.77	EC50	0.017	nM	CHEMBL3735858
10.77	EC50	0.017	nM	CHEMBL3736299
10.74	EC50	0.018	nM	CHEMBL3734932
10.74	EC50	0.018	nM	CHEMBL3736512
10.72	EC50	0.019	nM	CHEMBL3735812
10.66	EC50	0.022	nM	CHEMBL3735306
10.62	EC50	0.024	nM	CHEMBL2347510
10.62	EC50	0.024	nM	CHEMBL3736459
10.59	EC50	0.026	nM	CHEMBL2347512
10.54	EC50	0.029	nM	CHEMBL3736185
10.52	EC50	0.03	nM	CHEMBL3735210
10.51	EC50	0.031	nM	CHEMBL3735951
10.49	EC50	0.032	nM	CHEMBL2347496
10.48	EC50	0.033	nM	CHEMBL3734892
10.44	EC50	0.036	nM	CHEMBL2347498
10.44	EC50	0.036	nM	CHEMBL2347492
10.42	EC50	0.038	nM	CHEMBL2347508
10.40	EC50	0.04	nM	CHEMBL2347494
10.40	EC50	0.04	nM	CHEMBL2347509
10.39	EC50	0.041	nM	CHEMBL2347497
10.39	EC50	0.041	nM	CHEMBL3735225
10.37	EC50	0.043	nM	CHEMBL2347493
10.37	EC50	0.043	nM	CHEMBL3734921
10.34	EC50	0.046	nM	CHEMBL2347495
10.30	EC50	0.05	nM	CHEMBL3736198
10.29	EC50	0.051	nM	CHEMBL2347489
10.22	EC50	0.06	nM	CHEMBL2370235
10.20	EC50	0.063	nM	CHEMBL3736313
10.19	EC50	0.065	nM	CHEMBL2347488
10.19	EC50	0.064	nM	CHEMBL3736227
10.15	EC50	0.071	nM	CHEMBL2347506
10.14	EC50	0.072	nM	CHEMBL2347361
10.11	EC50	0.078	nM	CHEMBL2347662
10.10	Kd	0.08	nM	CHEMBL2311148
10.10	EC50	0.08	nM	CHEMBL2347511
10.10	EC50	0.079	nM	CHEMBL2347657
10.08	EC50	0.083	nM	CHEMBL2347659
10.08	EC50	0.084	nM	CHEMBL3735396
10.08	EC50	0.083	nM	CHEMBL3735963
10.07	EC50	0.085	nM	CHEMBL2347499
9.96	EC50	0.11	nM	CHEMBL2347501
9.92	EC50	0.12	nM	UPEROLEIN
9.89	EC50	0.13	nM	CHEMBL2347661

PubChem BioAssay actives

961 with measured affinity, of 1343 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
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	<0.0001	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-4-oxo-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]butanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-5-oxopentanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S,3R)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-[[(2S)-1-[(2S)-4-amino-4-oxo-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]butanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]-2-[[(2S)-1-[(2S)-3-hydroxy-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]butanediamide	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
N-[1-[3-[(3R)-1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-(3-tritiophenyl)piperidin-4-yl]-N-methylacetamide	715693: Binding affinity to human NK3 H316F mutant expressed in HEK293 cells assessed as [3H]IP accumulation after 45 mins	kd	0.0001	uM
(3S)-3-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-3-hydroxy-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0001	uM
(3S)-3-[[(2S)-6-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0002	uM
N-[1-[3-[(3R)-1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4-yl]-N-methylacetamide	1064185: Binding affinity to NK3 receptor (unknown origin)	ki	0.0002	uM
2-[3,5-bis(trifluoromethyl)phenyl]-N-[4-(4-fluoro-2-methylphenyl)-6-[(3S)-3-methyl-4-methylsulfonylpiperazin-1-yl]-3-pyridinyl]-N,2-dimethylpropanamide	715705: Displacement of radioligand [3H]osanetant at human NK3 Y315F6.51 mutant expressed in HEK293 cells	ki	0.0002	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0002	uM
3,5-dichloro-N-[(2Z,3R)-3-(3,4-dichlorophenyl)-2-methoxyimino-5-[4-[(3R)-3-[2-(methylamino)-2-oxoethyl]piperidin-1-yl]piperidin-1-yl]pentyl]-N-methylbenzamide	1525513: Displacement of [125I][MePhe]NKB from human NK3 receptor expressed in CHO cells membranes	ki	0.0003	uM
N-[(2Z,3R)-5-[4-[3-[(2R)-1-amino-3-hydroxy-1-oxopropan-2-yl]-2-oxo-1,3-diazinan-1-yl]piperidin-1-yl]-3-(3,4-dichlorophenyl)-2-methoxyiminopentyl]-3,5-dichloro-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0003	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0003	uM
N-[(2Z,3R)-5-[4-[3-(1-amino-2-methyl-1-oxopropan-2-yl)-2-oxo-1,3-diazinan-1-yl]piperidin-1-yl]-3-(3,4-dichlorophenyl)-2-methoxyiminopentyl]-3,5-dichloro-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0003	uM
3,5-dichloro-N-[(2Z,3R)-3-(3,4-dichlorophenyl)-2-methoxyimino-5-[4-[(3R)-3-[2-(methylamino)-2-oxoethyl]-2-oxopiperidin-1-yl]piperidin-1-yl]pentyl]-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0003	uM
(2S)-N-[(4-chlorophenyl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxospiro[3,1-benzoxazine-4,4’-piperidine]-1’-yl)-N-methylbutanamide	1155043: Displacement of [3H]-SR142801 from human NK3 receptor expressed in recombinant CHO cells	ki	0.0004	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	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0004	uM
3,5-dichloro-N-[(2Z,3R)-3-(3,4-dichlorophenyl)-5-[4-[3-[2-(methanesulfonamido)ethyl]-2-oxo-1,3-diazinan-1-yl]piperidin-1-yl]-2-methoxyiminopentyl]-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0004	uM
4-[4-[acetyl(propyl)amino]piperidin-1-yl]-2-(3,4-dichlorophenyl)-N-[(1R)-1-(4-fluorophenyl)-2-hydroxyethyl]-2-methylbutanamide	1155043: Displacement of [3H]-SR142801 from human NK3 receptor expressed in recombinant CHO cells	ki	0.0005	uM
(3S)-3-amino-4-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	738396: Agonist activity at NK3R (unknown origin) transfected in CHO cells assessed as calcium influx at 10 mM	ec50	0.0005	uM
3,5-dichloro-N-[(2Z,3R)-3-(3,4-dichlorophenyl)-5-[4-[3-(2-hydroxy-2-methylpropyl)-2-oxo-1,3-diazinan-1-yl]piperidin-1-yl]-2-methoxyiminopentyl]-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0005	uM
3,5-dichloro-N-[(2Z,3R)-3-(3,4-dichlorophenyl)-2-methoxyimino-5-[4-(2-oxo-3-pyridin-2-yl-1,3-diazinan-1-yl)piperidin-1-yl]pentyl]-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0005	uM
N-[(2Z,3R)-5-[4-[3-[(2Z)-2-amino-2-hydroxyiminoethyl]-2-oxo-1,3-diazinan-1-yl]piperidin-1-yl]-3-(3,4-dichlorophenyl)-2-methoxyiminopentyl]-3,5-dichloro-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0005	uM
3,5-dichloro-N-[(2Z,3R)-3-(3,4-dichlorophenyl)-2-methoxyimino-5-[4-(3-morpholin-4-yl-2-oxo-1,3-diazinan-1-yl)piperidin-1-yl]pentyl]-N-methylbenzamide	212246: Binding affinity against recombinant human tachykinin receptor 3 in CHO cells using [125I][MePhe]-NKB as radioligand	ki	0.0005	uM
2-[3,5-bis(trifluoromethyl)phenyl]-N-[4-(4-fluoro-2-methylphenyl)-6-[(2S)-2-(hydroxymethyl)-4-methylsulfonylpiperazin-1-yl]-3-pyridinyl]-N,2-dimethylpropanamide	715705: Displacement of radioligand [3H]osanetant at human NK3 Y315F6.51 mutant expressed in HEK293 cells	ki	0.0006	uM
2-[3,5-bis(trifluoromethyl)phenyl]-N-[4-(4-fluoro-2-methylphenyl)-6-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-3-pyridinyl]-N,2-dimethylpropanamide	715705: Displacement of radioligand [3H]osanetant at human NK3 Y315F6.51 mutant expressed in HEK293 cells	ki	0.0006	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects methylation	2
daidzein	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
arsenite	increases methylation	1
glycitein	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
(N-N’-bis-(2-(1H-indol-3-yl)-ethyl)-N,N’-bis-(3-thiomorpholin-4-yl-propyl)-phthalamide)	affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Alcohols	increases response to substance	1
Benzo(a)pyrene	increases methylation	1
Cocaine	increases response to substance	1
Copper	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Genistein	increases expression, affects cotreatment	1

ChEMBL screening assays

266 unique, capped per target: 217 binding, 48 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000188	Binding	Binding affinity to NK3 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1037632	Functional	Agonist activity at human NK3 receptor expressed in cells assessed as accumulation of [3H]inositol phosphate	Identification of a critical residue in the transmembrane domain 2 of tachykinin neurokinin 3 receptor affecting the dissociation kinetics and antagonism mode of osanetant (SR 142801) and piperidine-based structures. — J Med Chem
CHEMBL4322116	ADMET	Displacement of [125I][MePhe]NKB from human NK3 receptor expressed in CHO cells membranes	Rational Design of Multitarget-Directed Ligands: Strategies and Emerging Paradigms. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H472	CHO-K1/NK3	Spontaneously immortalized cell line	Female
CVCL_KV86	cAMP Hunter CHO-K1 TACR3 Gs/Gq	Spontaneously immortalized cell line	Female
CVCL_KZ19	PathHunter CHO-K1 TACR3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB37	PathHunter U2OS TACR3 Activated GPCR Internalization	Cancer cell line	Female
CVCL_YK60	U2OS TACR3 calcium-Nomad	Cancer cell line	Female
CVCL_YK61	U2OS TACR3 HiTSeeker	Cancer cell line	Female
CVCL_ZK25	Tango TACR3-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	PHASE4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	PHASE4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	PHASE3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	PHASE3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)