HTR1A

Summary

HTR1A (5-hydroxytryptamine receptor 1A, HGNC:5286) is a protein-coding gene on chromosome 5q12.3, encoding 5-hydroxytryptamine receptor 1A (P08908). G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

This gene encodes a G protein-coupled receptor for 5-hydroxytryptamine (serotonin), and belongs to the 5-hydroxytryptamine receptor subfamily. Serotonin has been implicated in a number of physiologic processes and pathologic conditions. Inactivation of this gene in mice results in behavior consistent with an increased anxiety and stress response. Mutation in the promoter of this gene has been associated with menstrual cycle-dependent periodic fevers.

Source: NCBI Gene 3350 — RefSeq curated summary.

At a glance

• Gene–disease (curated): menstrual cycle-dependent periodic fever (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 65 total
• Phenotypes (HPO): 5
• Druggable target: yes — 401 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000524

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5286
Approved symbol	HTR1A
Name	5-hydroxytryptamine receptor 1A
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	5-HT1A
Ensembl gene	ENSG00000178394
Ensembl biotype	protein_coding
OMIM	109760
Entrez	3350

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000323865, ENST00000506598

RefSeq mRNA: 1 — MANE Select: NM_000524 NM_000524

CCDS: CCDS34168

Canonical transcript exons

ENST00000323865 — 1 exons

Exon	Start	End
ENSE00001285047	63957874	63962445

Expression profiles

Bgee: expression breadth broad, 66 present calls, max score 84.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2714 / max 43.0608, expressed in 58 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61926	0.1490	46
61929	0.0391	12
61930	0.0336	9
61927	0.0278	18
61928	0.0220	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
entorhinal cortex	UBERON:0002728	84.24	gold quality
middle temporal gyrus	UBERON:0002771	83.54	gold quality
cortical plate	UBERON:0005343	83.30	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.53	gold quality
superior vestibular nucleus	UBERON:0007227	76.57	gold quality
superior frontal gyrus	UBERON:0002661	75.85	gold quality
Ammon’s horn	UBERON:0001954	74.90	gold quality
prefrontal cortex	UBERON:0000451	74.35	gold quality
endothelial cell	CL:0000115	74.20	silver quality
frontal cortex	UBERON:0001870	73.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	73.28	gold quality
cerebral cortex	UBERON:0000956	73.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.01	gold quality
postcentral gyrus	UBERON:0002581	72.52	gold quality
neocortex	UBERON:0001950	71.91	gold quality
temporal lobe	UBERON:0001871	71.63	gold quality
parietal lobe	UBERON:0001872	71.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.97	gold quality
right frontal lobe	UBERON:0002810	69.67	gold quality
anterior cingulate cortex	UBERON:0009835	67.55	gold quality
primary visual cortex	UBERON:0002436	65.15	gold quality
occipital lobe	UBERON:0002021	64.01	gold quality
amygdala	UBERON:0001876	63.33	gold quality
ganglionic eminence	UBERON:0004023	61.71	gold quality
forebrain	UBERON:0001890	61.12	gold quality
adult organism	UBERON:0007023	61.09	gold quality
medulla oblongata	UBERON:0001896	59.48	gold quality
hypothalamus	UBERON:0001898	58.50	gold quality
brain	UBERON:0000955	57.45	gold quality
pancreatic ductal cell	CL:0002079	57.03	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CC2D1A, CC2D1B, DEAF1, FEV, HES1, HES5, HES6, MAZ, NFKB1, NR3C1, NR3C2, PARP1, PITX2, POU6F1, RELA, REST, SP1, TBX15, ZNF362

miRNA regulators (miRDB)

21 targeting HTR1A, 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-5698	99.97	68.49	2029
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-6888-5P	95.89	63.78	831

Literature-anchored findings (GeneRIF, showing 40)

• increased serotonin-1A receptor binding in type 2 diabetes (PMID:11814436)
• Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues. (PMID:11989622)
• it is unlikely that the 5-HT1A receptor gene is implicated in the susceptibility to suicide (PMID:11992564)
• low but not high concentrations of high-efficacy 5-HT(1A) agonists direct receptor signaling to Galpha(i3). (PMID:12181435)
• In basal epidermal cells in contact eczematous skin. In upper epidermis, with no difference between eczematous and control skin. In papillary dermal mononuclear cells in inflamed skin and control skin and in vessel walls. (PMID:12522576)
• Changes in agonist-stimulated 5-HT1A receptor activation in depressed suicide victims are manifest downstream from associated G proteins, affecting activity of second messengers in two 5-HT1A receptor transduction pathways that may affect cell survival (PMID:12969265)
• We report association of the C(-1019)G 5-HT1A promoter polymorphism with major depression and suicide in separate cohorts; NUDR protein represses the 5-HT1A receptor in raphe cells (PMID:14507979)
• The data do not support the proposal that decreased 5-HT(1A) receptor binding potential in patients with acute major depression is a consequence of cortisol hypersecretion. (PMID:14573316)
• Central 5-HT(1A)receptor binding using positron emission tomography and the selective radioligand 18F]-FCWAY provided evidence for the involvement of 5-HT(1A)receptors in the pathophysiology of panic disorder. (PMID:14736842)
• Alterations in 5-HT(1A,) 5-HT(1B), and 5-HT(2A) mRNA levels in the brains of subjects with both mood disorders and schizophrenia add further support for hypothesis of dysregulation of the serotonergic system in these psychiatric disorders. (PMID:14744462)
• a possible role of 5-HT1A gene polymorphism in the subgroup of panic-disorder patients with agoraphobia. (PMID:14984628)
• A significant increase in 5-HT1A receptor binding density is observed in the infant medulla in the hypoglossal nucleus, and a marginally significant increase is observed in the raphe obscurus. (PMID:15048689)
• Patients with severe mesial temporal lobe epilepsy show reduced 5-HT1A receptor binding potential in the EEG-focus, and its limbic connections. (PMID:15111672)
• effects of a 5-hydroxytryptamine (5-HT) 1A receptor gene polymorphism on the clinical response to fluvoxamine (FLV) in 65 depressed outpatients (PMID:15148501)
• data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population (PMID:15211620)
• 5-HT1A gene polymorphism is a potential marker for antidepressant response, suggesting a role for repression of the 5-HT1A gene (PMID:15447813)
• 5-HT1A variants could influence the antidepressant efficacy in bipolar subjects (PMID:15458611)
• 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype (PMID:15469667)
• 5-HT1A receptor exhibits detergent insolubility. (PMID:15498580)
• When cloned into Xenopus oocytes, activate calcium-activated potassium channels (PMID:15521063)
• This study findings suggest that this 5-HT1A polymorphism may affect AEP P2 latency in a gender-dependent manner. (PMID:15539859)
• multiple lines of evidence implicate the 5-HT1A receptor in the pathophysiology of anxiety and depression as well as in the mechanism of action of anxiolytics/antidepressants–REVIEW (PMID:15683551)
• With white matter as a reference region, nonspecific equilibrium partition coefficient (V(3)’’) cannot be used to detect differences in 5-HT(1A) receptors between men and women (PMID:15716853)
• the combined effect of the serotonin transporter and the 5-HT(1A) receptor genes could be related to the clinical outcome of depressive patients treated with citalopram (PMID:15728438)
• the Arg219Leu variation of the human 5-HT1A receptor does not change the binding properties, but is associated with a drastic impairment of signal transduction (PMID:15864118)
• An increase in receptor densisty may inhibit function of the anterior cingulate, thus contributing to heightened amygdala response. (PMID:15940302)
• 5-HT(1A)*C/C genotype in a sample of 40 remitted mood disorder patients showed significantly lower scores at the total self-transcendence and at the sub-scales of transpersonal identification and spiritual acceptance. (PMID:15952185)
• In this review, critical factors determining functional solubilization of membrane proteins are highlighted with the solubilization of the serotonin 1A receptor taken as a specific example. (PMID:16081372)
• The GG genotype is overrepresented in major depressive disorder, and binding potential appears higher with the G allele. (PMID:16154547)
• HTR1A -1019C/C carriers showed a better response to fluoxetine. (PMID:16302021)
• In panic disorder patients homozygous for the 5-HT1A-1019G risk allele fearful stimuli were associated with a decreased activation of right prefrontal cortex regions. (PMID:16316476)
• Cell-specific regulation by Deaf-1 could underlie region-specific alterations in 5-HT1A receptor expression in different mood disorders. (PMID:16467535)
• The observed reduction in hippocampal 5-HT1A receptor binding in male offspring after prenatal stress may have important consequences for adult anxiety- and depressive-like behavior. (PMID:16677618)
• The frequenct of single-nucleotide polymorphism did not vary significantly in migraine patients, and is thus not a genetic risk factor. (PMID:16722981)
• Fluctuation in the level of SPS is a risk factor for the onset of flare in SLE patients with major renal manifestations when it occurs on the background of a stress-related susceptibility gene (the 5-HT1A -1019 G allele). (PMID:17009264)
• 5-HT1A receptors are involved in verbal memory function. (PMID:17092965)
• This result demonstrates that the cell surface dynamics of the serotonin(1A) receptor is modulated in a G-protein-dependent manner. (PMID:17123166)
• HTR2C and HTR1A gene variants are not major contributors to suicide-, anger-, or aggression-related behaviors. (PMID:17192951)
• 5-HT1A receptor stimulates both extracellular signal regulated protein kinase-dependent anti-apoptotic pathways and c-Jun N-terminal kinase-dependent pro-apoptotic pathways in CHO cells (PMID:17208318)
• The combination of 5-HT1A GG and BDNF GA + AA genotypes is associated with an increased risk of depression. (PMID:17401528)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr1ab	ENSDARG00000057098
mus_musculus	Htr1a	ENSMUSG00000021721
caenorhabditis_elegans		WBGENE00004779

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

5-hydroxytryptamine receptor 1A — P08908 (reviewed: P08908)

Alternative names: G-21, Serotonin receptor 1A

All UniProt accessions (3): P08908, D6RA34, Q5ZGX3

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.

Subunit / interactions. Heterodimer; heterodimerizes with GPER1. Interacts with YIF1B. Interacts with GPR39 and GALR1.

Subcellular location. Cell membrane. Cell projection. Dendrite.

Tissue specificity. Detected in lymph nodes, thymus and spleen. Detected in activated T-cells, but not in resting T-cells.

Disease relevance. Periodic fever, menstrual cycle-dependent (PFMC) [MIM:614674] A condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. G-protein coupled receptor activity is regulated by lipids: phosphatidylinositol 4-phosphate increases HTR1A-mediated activity. Binding to aripiprazol drug is regulated by cholesterol, which shapes the ligand-binding pocket, determining the specificity for aripiprazol. Activated by IHCH-7179 small molecule: IHCH-7179 acts both as an agonist activator for HTR1A and as an antagonist inhibitor for HTR2A. Activated by SEP-363856 small molecule: IHCH-7179 acts both as an agonist activator for HTR1A and TAAR1.

Similarity. Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.

RefSeq proteins (1): NP_000515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000610	5HT1A_rcpt	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (69 total): helix 13, binding site 9, topological domain 8, sequence conflict 8, transmembrane region 7, sequence variant 6, mutagenesis site 5, glycosylation site 3, turn 3, region of interest 2, short sequence motif 2, chain 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
9HYI	ELECTRON MICROSCOPY	2.3
8PJK	ELECTRON MICROSCOPY	2.4
9VJE	ELECTRON MICROSCOPY	2.47
9KVI	ELECTRON MICROSCOPY	2.54
9KVH	ELECTRON MICROSCOPY	2.59
8FYX	ELECTRON MICROSCOPY	2.62
9VJ6	ELECTRON MICROSCOPY	2.62
9KVG	ELECTRON MICROSCOPY	2.63
8FYT	ELECTRON MICROSCOPY	2.64
9VJG	ELECTRON MICROSCOPY	2.67
9VJ5	ELECTRON MICROSCOPY	2.69
9VJF	ELECTRON MICROSCOPY	2.7
9DYF	ELECTRON MICROSCOPY	2.74
9VNF	ELECTRON MICROSCOPY	2.74
8FY8	ELECTRON MICROSCOPY	2.79
8FYE	ELECTRON MICROSCOPY	2.85
9VMY	ELECTRON MICROSCOPY	2.86
8PKM	ELECTRON MICROSCOPY	2.9
9DYE	ELECTRON MICROSCOPY	2.9
8FYL	ELECTRON MICROSCOPY	2.94
9DYD	ELECTRON MICROSCOPY	2.96
7E2X	ELECTRON MICROSCOPY	3
7E2Y	ELECTRON MICROSCOPY	3
8JT6	ELECTRON MICROSCOPY	3
8W8B	ELECTRON MICROSCOPY	3
9MD1	ELECTRON MICROSCOPY	3.03
7E2Z	ELECTRON MICROSCOPY	3.1
9GL2	ELECTRON MICROSCOPY	3.2
8JSP	ELECTRON MICROSCOPY	3.65
9R41	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08908-F1	78.68	0.52

Antibody-complex structures (SAbDab): 6 — 8JSP, 8JT6, 8W8B, 9KVG, 9VJE, 9VJF

Functional residue map

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

Ligand- & substrate-binding residues (9): 116; 120; 314; 345; 346; 352; 403; 404; 405

Disulfide bonds (1): 109–187

Glycosylation sites (3): 10, 11, 24

Mutagenesis-validated functional residues (5):

Position	Phenotype
134	reduced activation of g proteins.
191	increased activation of g alpha proteins in response to sep363856-binding.
345	reduced activation of g proteins.
365	reduced g(i)/(o)-coupled receptor activity.
405	reduced activation of g proteins.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-390666	Serotonin receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 162 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, HOEGERKORP_CD44_TARGETS_TEMPORAL_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_AMINE_METABOLIC_PROCESS, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_CELL_CELL_SIGNALING

GO Biological Process (19): behavioral fear response (GO:0001662), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), serotonin receptor signaling pathway (GO:0007210), gamma-aminobutyric acid signaling pathway (GO:0007214), chemical synaptic transmission (GO:0007268), positive regulation of cell population proliferation (GO:0008284), regulation of serotonin secretion (GO:0014062), regulation of vasoconstriction (GO:0019229), adult behavior (GO:0030534), exploration behavior (GO:0035640), regulation of dopamine metabolic process (GO:0042053), serotonin metabolic process (GO:0042428), regulation of hormone secretion (GO:0046883), regulation of behavior (GO:0050795), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), G protein-coupled serotonin receptor signaling pathway (GO:0098664)

GO Molecular Function (8): Gi/o-coupled serotonin receptor activity (GO:0001586), G protein-coupled serotonin receptor activity (GO:0004993), neurotransmitter receptor activity (GO:0030594), serotonin binding (GO:0051378), receptor-receptor interaction (GO:0090722), serotonin receptor activity (GO:0099589), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), dendrite (GO:0030425), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Amine ligand-binding receptors	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
behavior	3
signal transduction	2
G protein-coupled serotonin receptor signaling pathway	2
regulation of secretion by cell	2
G protein-coupled serotonin receptor activity	2
transmembrane signaling receptor activity	2
cellular anatomical structure	2
behavioral defense response	1
fear response	1
G protein-coupled receptor activity	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
serotonin receptor activity	1
cellular response to dopamine	1
cell-cell signaling	1
GABA receptor activity	1
anterograde trans-synaptic signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
serotonin secretion	1
regulation of monoatomic ion transport	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
regulation of catecholamine metabolic process	1
dopamine metabolic process	1
phenol-containing compound metabolic process	1
indole-containing compound metabolic process	1
regulation of cell communication	1
regulation of hormone levels	1
regulation of signaling	1
hormone secretion	1
regulation of multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1

Protein interactions and networks

STRING

1880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR1A	SLC6A4	P31645	968
HTR1A	FGFR1	P11362	887
HTR1A	HTR2A	P28223	879
HTR1A	HTR1B	P28222	873
HTR1A	MAOA	P21397	862
HTR1A	BDNF	P23560	806
HTR1A	GALR1	P47211	800
HTR1A	SLC6A3	Q01959	787
HTR1A	GPR55	Q9Y2T6	782
HTR1A	SLC6A2	P23975	781
HTR1A	HTR3A	P46098	735
HTR1A	TRPV1	Q8NER1	735
HTR1A	GRM4	Q14833	733
HTR1A	CRH	P06850	729
HTR1A	MAOB	P27338	727

IntAct

28 interactions, top by confidence:

A	B	Type	Score
FGFR1	HTR1A	psi-mi:“MI:2364”(proximity)	0.620
HTR1A	FGFR1	psi-mi:“MI:2364”(proximity)	0.620
HTR1A	FGFR1	psi-mi:“MI:0915”(physical association)	0.620
FGFR1	HTR1A	psi-mi:“MI:0915”(physical association)	0.620
GALR1	HTR1A	psi-mi:“MI:0403”(colocalization)	0.590
GALR1	HTR1A	psi-mi:“MI:2364”(proximity)	0.590
GPR39	HTR1A	psi-mi:“MI:0403”(colocalization)	0.570
GPR39	HTR1A	psi-mi:“MI:2364”(proximity)	0.570
GPR39	HTR1A	psi-mi:“MI:0915”(physical association)	0.570
HTR1A	GPR39	psi-mi:“MI:0914”(association)	0.570
HTR1A	HTR1A	psi-mi:“MI:2364”(proximity)	0.510
HTR1A	SARNP	psi-mi:“MI:0915”(physical association)	0.400
	HTR1A	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	HTR1A	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR1A	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HTR1A	psi-mi:“MI:0915”(physical association)	0.400
HTR1A	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
HTR1A	HTR2A	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (38): FGFR1 (Affinity Capture-Western), HTR1A (Affinity Capture-Western), FGFR1 (Biochemical Activity), HTR1A (FRET), HTR1A (Co-localization), SARNP (Proximity Label-MS), HTR1D (Affinity Capture-Western), S1PR3 (Affinity Capture-Western), GPR26 (Affinity Capture-Western), S1PR1 (Affinity Capture-Western), HTR1A (Affinity Capture-Western), PPP1CC (Affinity Capture-MS), RPLP0 (Affinity Capture-MS), PAWR (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS)

ESM2 similar proteins: G3M4F8, O02213, O08890, O42384, O42385, O42574, O70528, O73810, P08908, P14416, P19327, P20288, P21728, P28222, P28334, P28564, P30939, P30940, P35404, P46636, P49144, P52702, P56496, P60020, P60026, P61168, P61169, P79748, P97288, Q02284, Q0EAB5, Q0EAB6, Q13639, Q588Y6, Q62758, Q64264, Q6TLI9, Q6XXX8, Q8JG69, Q8JG70

Diamond homologs: A0T2N3, A6QLE7, O02213, O15973, O19091, O46635, O60755, O77621, O77721, P08908, P08909, P0C5J4, P11613, P14842, P18599, P19327, P22270, P25102, P28223, P28286, P34968, P35363, P41595, P46093, P50128, P50129, P50132, P56481, P79960, Q0EAB6, Q1JQB3, Q25321, Q25322, Q2TAD5, Q4KLH9, Q4LBB6, Q4VA82, Q5IS66, Q5R4Q6, Q60F97

SIGNOR signaling

83 interactions.

A	Effect	B	Mechanism
8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione	down-regulates	HTR1A	“chemical inhibition”
N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide	down-regulates	HTR1A	“chemical inhibition”
DEAF1	“down-regulates quantity by repression”	HTR1A	“transcriptional regulation”
HTR1A	“up-regulates activity”	GNAI1	binding
HTR1A	“up-regulates activity”	GNAI3	binding
HTR1A	“up-regulates activity”	GNAO1	binding
HTR1A	“up-regulates activity”	GNAQ	binding
HTR1A	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR1A	“chemical activation”
serotonin	“up-regulates activity”	HTR1A	“chemical activation”
CC2D1A	“down-regulates quantity by repression”	HTR1A	“transcriptional regulation”
CC2D1B	“down-regulates quantity by repression”	HTR1A	“transcriptional regulation”
ziprasidone	“up-regulates activity”	HTR1A	“chemical activation”
olanzapine	“up-regulates activity”	HTR1A	“chemical activation”
clozapine	“up-regulates activity”	HTR1A	“chemical activation”
haloperidol	“down-regulates activity”	HTR1A	“chemical inhibition”
risperidone	“down-regulates activity”	HTR1A	“chemical inhibition”
quetiapine	“up-regulates activity”	HTR1A	“chemical activation”
8-[4,4-bis(4-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	“down-regulates activity”	HTR1A	“chemical inhibition”
sertindole	“down-regulates activity”	HTR1A	“chemical inhibition”
zotepine	“down-regulates activity”	HTR1A	“chemical inhibition”
paliperidone	“down-regulates activity”	HTR1A	“chemical inhibition”
(S,S)-asenapine	“up-regulates activity”	HTR1A	“chemical activation”
pipamperone	“down-regulates activity”	HTR1A	“chemical inhibition”
YIF1B	“up-regulates activity”	HTR1A	relocalization
lurasidone	“up-regulates activity”	HTR1A	“chemical activation”
propranolol	“down-regulates activity”	HTR1A	“chemical inhibition”
lisuride	“up-regulates activity”	HTR1A	“chemical activation”
methysergide	“up-regulates activity”	HTR1A	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	11
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

16 predictions. Top by Δscore:

Variant	Effect	Δscore
5:63961860:A:AC	donor_gain	0.7900
5:63961861:C:CC	donor_gain	0.7900
5:63961861:CTG:C	donor_gain	0.6900
5:63961483:C:CT	acceptor_gain	0.5700
5:63961766:G:GT	acceptor_gain	0.5500
5:63961856:T:A	donor_gain	0.5500
5:63961759:G:GT	acceptor_gain	0.4000
5:63961862:T:C	donor_gain	0.3700
5:63961765:C:T	acceptor_gain	0.3300
5:63960696:T:TA	donor_gain	0.3200
5:63961661:T:TG	acceptor_gain	0.3200
5:63961662:C:G	acceptor_gain	0.2900
5:63961853:AGTT:A	donor_gain	0.2500
5:63960690:CTGT:C	donor_gain	0.2300
5:63961732:G:T	acceptor_gain	0.2300
5:63960753:TCTC:T	acceptor_gain	0.2000

AlphaMissense

2737 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:63960532:G:C	N396K	1.000
5:63960532:G:T	N396K	1.000
5:63960544:G:C	N392K	1.000
5:63960544:G:T	N392K	1.000
5:63960554:C:T	G389D	1.000
5:63960555:C:G	G389R	1.000
5:63960561:A:G	W387R	1.000
5:63960561:A:T	W387R	1.000
5:63960634:G:C	F362L	1.000
5:63960634:G:T	F362L	1.000
5:63960636:A:G	F362L	1.000
5:63960637:G:C	F361L	1.000
5:63960637:G:T	F361L	1.000
5:63960639:A:G	F361L	1.000
5:63960641:G:C	P360R	1.000
5:63960641:G:T	P360H	1.000
5:63960644:A:G	L359P	1.000
5:63960648:A:G	W358R	1.000
5:63960648:A:T	W358R	1.000
5:63960658:G:C	F354L	1.000
5:63960658:G:T	F354L	1.000
5:63960660:A:G	F354L	1.000
5:63960666:C:G	G352R	1.000
5:63960677:C:T	G348D	1.000
5:63960680:A:G	L347P	1.000
5:63961100:G:T	P207Q	1.000
5:63961108:G:C	F204L	1.000
5:63961108:G:T	F204L	1.000
5:63961110:A:G	F204L	1.000
5:63961159:G:C	C187W	1.000

dbSNP variants (sampled 300 via entrez): RS1000530392 (5:63959526 A>G), RS1000782818 (5:63959769 G>T), RS1000832127 (5:63959980 G>A), RS1002872656 (5:63964270 T>A,G), RS1002897207 (5:63963947 C>A), RS1003441769 (5:63957739 C>G,T), RS1004137045 (5:63958469 T>C), RS10052087 (5:63959118 A>C), RS1005289061 (5:63959411 C>A,T), RS1006329991 (5:63963444 C>G,T), RS1006444073 (5:63963935 C>G,T), RS1006478951 (5:63958572 G>C), RS1006531454 (5:63958860 G>A,T), RS1006755471 (5:63964434 T>C), RS1007180836 (5:63958571 G>A)

Disease associations

OMIM: gene MIM:109760 | disease phenotypes: MIM:614674

GenCC curated gene-disease

Disease	Classification	Inheritance
menstrual cycle-dependent periodic fever	Limited	Autosomal dominant

Mondo (1): menstrual cycle-dependent periodic fever (MONDO:0044660)

Orphanet (1): Menstrual cycle-dependent periodic fever (Orphanet:498251)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001945	Fever
HP:0002076	Migraine
HP:0003118	Increased circulating cortisol level
HP:0200067	Recurrent spontaneous abortion

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000830_37	Body mass index	1.000000e-06
GCST001769_2	Alcohol and nicotine co-dependence	1.000000e-09
GCST002104_8	Bronchopulmonary dysplasia	6.000000e-06
GCST002248_7	Fasting insulin (dietary factor interaction)	9.000000e-10
GCST002253_9	Homeostasis model assessment of insulin resistance (dietary factor interaction)	1.000000e-09
GCST003151_6	White matter lesion progression	6.000000e-06
GCST003152_6	White matter lesion progression (adjusted for white matter lesion burden at baseline)	8.000000e-06
GCST010988_90	Adult body size	3.000000e-14
GCST011494_18	Daytime nap	6.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008111	diet measurement
EFO:0004501	HOMA-IR
EFO:0007746	white matter lesion progression measurement
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2096904 (PROTEIN FAMILY), CHEMBL2111460 (SELECTIVITY GROUP), CHEMBL214 (SINGLE PROTEIN), CHEMBL4523958 (SELECTIVITY GROUP), CHEMBL4524122 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

401 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 422,686 (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
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1075	MORICIZINE	4	3,860
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1093	ARTICAINE	4	6,583
CHEMBL1106	EPINASTINE	4	8,530
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL117287	PRUCALOPRIDE	4	2,516
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL117785	TETRABENAZINE	4	9,645
CHEMBL1185	ZOLMITRIPTAN	4	13,569
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4
CHEMBL1200596	CHLOROXINE	4
CHEMBL1200666	CALCIPOTRIENE	4
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4
CHEMBL1200791	OXYMETAZOLINE HYDROCHLORIDE	4
CHEMBL1200938	METHYSERGIDE MALEATE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL1201087	CABERGOLINE	4
CHEMBL1201196	SERTACONAZOLE	4
CHEMBL1201210	PROPIOMAZINE	4

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

PharmGKB clinical annotations

10 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10042486	Efficacy	3	fluvoxamine;milnacipran;paroxetine	Major Depressive Disorder
rs10042486	Efficacy	3	amisulpride;antipsychotics;olanzapine;quetiapine;risperidone	Schizophrenia
rs1364043	Efficacy	3	fluvoxamine;milnacipran;paroxetine	Major Depressive Disorder
rs6295	Efficacy	3	antidepressants;fluvoxamine;paroxetine;Selective serotonin reuptake inhibitors;sertraline	Depressive Disorder;Major Depressive Disorder
rs6295	Efficacy	3	fluoxetine	Major Depressive Disorder
rs6295	Efficacy	3	clozapine	Schizophrenia
rs6295	Efficacy	3	milnacipran	Depressive Disorder
rs6295	Efficacy	3	lurasidone	Schizophrenia
rs6295	Efficacy	3	paroxetine	Panic Disorder
rs878567	Toxicity	3	methamphetamine	Substance-Related Disorders

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6295	HTR1A	3	5.75	6	antidepressants;fluvoxamine;paroxetine;Selective serotonin reuptake inhibitors;sertraline;clozapine;paroxetine;fluoxetine;milnacipran;lurasidone
rs878567	HTR1A	3	3.00	1	methamphetamine
rs1364043	HTR1A	3	2.00	1	fluvoxamine;milnacipran;paroxetine
rs1800042	HTR1A		0.00	0
rs10042486	HTR1A	3	3.00	2	amisulpride;antipsychotics;olanzapine;quetiapine;risperidone;fluvoxamine;milnacipran;paroxetine

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — 5-Hydroxytryptamine receptors

Most potent curated ligand interactions (119 total), top 25:

Ligand	Action	Affinity	Parameter
S-14671	Full agonist	10.5	pKi
5-CT	Full agonist	10.3	pKi
LY293284	Full agonist	10.1	pKi
roxindole	Partial agonist	9.9	pKi
lisuride	Full agonist	9.8	pKi
[3H]robalzotan	Antagonist	9.8	pKd
S-14506	Full agonist	9.7	pKi
U92016A	Full agonist	9.7	pKi
5-hydroxytryptamine	Full agonist	9.7	pKi
Rec 15/3079	Antagonist	9.7	pKi
vilazodone	Partial agonist	9.52	pIC50
[3H]WAY100635	Antagonist	9.5	pKd
[3H]8-OH-DPAT	Full agonist	9.4	pKd
NAN 190	Antagonist	9.4	pKi
repinotan	Antagonist	9.4	pKi
8-OH-DPAT	Full agonist	9.4	pKi
flesinoxan	Full agonist	9.3	pKi
L-694,247	Full agonist	9.3	pKi
S-15535	Partial agonist	9.2	pKi
robalzotan	Antagonist	9.2	pKi
WAY-100635	Antagonist	9.2	pKi
Lysergide	Full agonist	9.0	pKi
RU 24969	Full agonist	9.0	pKi
flibanserin	Agonist	9.0	pKi
LY 165,163	Full agonist	8.9	pKi

Binding affinities (BindingDB)

832 measured of 973 human assays (1026 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(4-methoxyphenyl)-4-(2-thienylsulfonyl)piperazine	EC50	0.00713 nM
6-chloranyl-2-(4-methylpiperazin-1-yl)-4-phenyl-quinazoline	EC50	0.00913 nM
2-[4-(8-ethoxy-3,4-dihydro-1H-[1]benzofuro[2,3-c]pyridin-2-yl)butyl]-4-methyl-1,2,4-triazine-3,5-dione	KI	0.015 nM	US-20250109139: TRICYCLIC COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF
2-[4-(8-methoxy-3,4-dihydro-1H-[1]benzofuro[2,3-c]pyridin-2-yl)butyl]-4-methyl-1,2,4-triazine-3,5-dione	KI	0.073 nM	US-20250109139: TRICYCLIC COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF
3-(3-(4-(4-(4-oxofuro[3,2-c]pyridin-5 (4H)-yl)phenyl)piperazin-1-yl)propyl)-1H-indole-5-carbonitrile	KI	0.1 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
NSC_104911	KI	0.1 nM
roxindole	KI	0.11 nM
3-(4-(4-(4-(4-oxofuro[3,2-c]pyridin-5 (4H)-yl)phenyl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.14 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]urea	KI	0.15 nM
4-methyl-2-[4-(4-phenylpiperazin-1-yl)butyl]-1,2,4-triazine-3,5-dione	KI	0.15 nM	US-9290463: Radiolabeled compounds and uses thereof
3-(4-(4-(4-(3,5-difluoro-2-oxopyridin-1(2H)-yl)phenyl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.18 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
1-(4-(4-(4-(5-fluoro-1H-indol-3-yl)butyl)piperazin-1-yl)phenyl)pyridin-2(1H)-one	KI	0.19 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
3-(3-(4-(4,6-Dimethoxypyrimidin-2-yl)piperazin-1-yl)propyl)-5-methoxy-1H-indole	KI	0.19 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
3-(3-(4-(4-(Trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)propyl)-1H-indole-5-carbonitrile	KI	0.2 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
ethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.2 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
NSC_121851	KI	0.2 nM
6-(2-(4-(benzo[b]thiophen-4-yl)piperidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.223 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
3-(4-(4-(4-(2-oxopyridin-1(2H)-yl)phenyl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.23 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
1,1-Dioxo-2-[4-(4-pyrimidin-2-yl-piperazin-1-yl)-butyl]-1,2-dihydro-1lambda6-benzo[d]isothiazol-3-one	KI	0.23 nM
5-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one	EC50	0.235 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
6-[2-[4-[(4-bromo-3-hydroxyphenyl)methyl]piperidin-1-yl]ethyl]chromen-4-one	KI	0.27 nM	US-8778970: Benzyl piperidine compound
Ethyl 2-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-4-methylthiazole-5-carboxylate	KI	0.27 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
3-(3-(4-(4,6-Dimethylpyrimidin-2-yl)piperazin-1-yl)propyl)-5-methoxy-1H-indole	KI	0.29 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
Ethyl 2-(4-(3-(5-cyano-1H-indol-3-yl)propyl)piperazin-1-yl)-4-methylthiazole-5-carboxylate	KI	0.3 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
(S,S)-reboxetine	KI	0.3 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
3-(3-(4-(4-(3,5-difluoro-2-oxopyridin-1(2H)-yl)phenyl)piperazin-1-yl)propyl)-1H-indole-5-carbonitrile	KI	0.31 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
p-MPPI	KI	0.32 nM
(1R,3R,5S)-8-((S)-8-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-3-(3-trifluoromethyl-phenyl)-8-aza-bicyclo[3.2.1]octan-3-ol	KI	0.33 nM
Urapidil-5-methyl	KI	0.35 nM
5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.379 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
7-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.397 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
5-[2-(8-ethoxy-3,4-dihydro-1H-[1]benzofuro[2,3-c]pyridin-2-yl)ethyl]-1-methyl-7,8-dihydro-6H-pyrazolo[4,5-c]azepin-4-one	KI	0.42 nM	US-20250109139: TRICYCLIC COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF
3-(4-(4-(4-(4-methyl-2-oxopyridin-1(2H)-yl)phenyl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.48 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
3-(4-(4-(4-(5-oxo-1,6-naphthyridin-6(5H)-yl)phenyl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.5 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-pyrrole-2-carboxamide	KI	0.52 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
phenyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.58 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
6-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.599 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine	KI	0.6 nM
FLESINOXAN	KI	0.6 nM
N-(5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-yl)acetamide	EC50	0.602 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
3-(3-(4-(4-(4-methoxy-2-oxopyridin-1(2H)-yl)phenyl)piperazin-1-yl)propyl)-1H-indole-5-carbonitrile	KI	0.61 nM	US-9714232: Substituted piperazine compounds and methods of use thereof
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.626 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
7-[2-(8-ethoxy-3,4-dihydro-1H-[1]benzofuro[2,3-c]pyridin-2-yl)ethyl]-1H-quinolin-2-one	KI	0.64 nM	US-20250109139: TRICYCLIC COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF
3-(4-(4-(4-Methoxy-6-methylpyrimidin-2-yl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.65 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
CAS_141533-35-9	KI	0.66 nM
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]thiazin-3(4H)-one	EC50	0.68 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
3-(4-(4-(4-(Trifluoromethyl)pyrimidin-2-yl)piperazin-1-yl)butyl)-1H-indole-5-carbonitrile	KI	0.7 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof
5-Chloro-3-(3-(4-(4,6-dimethylpyrimidin-2-yl)piperazin-1-yl)propyl)-1H-indole	KI	0.71 nM	US-9598401: Substituted heteroaryl compounds and methods of use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	EC50	0.01	nM	CHEMBL199824
11.00	Ki	0.01	nM	CHEMBL4790600
10.99	EC50	0.01023	nM	CHEMBL4790600
10.89	Ki	0.01288	nM	CHEMBL4746386
10.88	EC50	0.01318	nM	CHEMBL4757755
10.86	EC50	0.0138	nM	CHEMBL4755058
10.85	Ki	0.0141	nM	CHEMBL1258761
10.83	Ki	0.01479	nM	CHEMBL4742112
10.82	Ki	0.0152	nM	CHEMBL1258533
10.80	Ki	0.01585	nM	CHEMBL4760271
10.78	Ki	0.0166	nM	CHEMBL4739908
10.69	Ki	0.02042	nM	CHEMBL4752833
10.64	Ki	0.023	nM	CHEMBL4739908
10.60	Ki	0.02512	nM	CHEMBL4759759
10.60	EC50	0.02512	nM	CHEMBL4752177
10.55	Ki	0.028	nM	CHEMBL511857
10.54	Ki	0.029	nM	CHEMBL6060586
10.53	Ki	0.02951	nM	CHEMBL4777581
10.53	EC50	0.02951	nM	CHEMBL4756233
10.52	Ki	0.03	nM	CHEMBL271987
10.52	Ki	0.03	nM	CHEMBL6039332
10.52	Ki	0.03	nM	CHEMBL5888355
10.51	Ki	0.0309	nM	CHEMBL4751777
10.50	Ki	0.03162	nM	CHEMBL4790662
10.50	EC50	0.03162	nM	CHEMBL1290716
10.47	Ki	0.03388	nM	CHEMBL4796345
10.47	Ki	0.03388	nM	CHEMBL4754941
10.46	Ki	0.035	nM	CHEMBL4751777
10.40	Ki	0.04	nM	CHEMBL5177580
10.40	Ki	0.04	nM	CHEMBL45422
10.37	Ki	0.043	nM	CHEMBL4797282
10.35	Ki	0.04467	nM	CHEMBL4757755
10.35	Ki	0.04467	nM	CHEMBL5868777
10.35	Ki	0.0447	nM	CHEMBL1258648
10.32	Ki	0.04786	nM	CHEMBL4797282
10.30	EC50	0.05	nM	CHEMBL199824
10.30	Ki	0.05	nM	CHEMBL5868777
10.30	Ki	0.05012	nM	CHEMBL5832273
10.30	Ki	0.0501	nM	CHEMBL1257734
10.30	Ki	0.0504	nM	CHEMBL1258879
10.28	Ki	0.052	nM	CHEMBL4786067
10.28	Ki	0.05248	nM	CHEMBL5886130
10.27	Ki	0.0537	nM	CHEMBL4752177
10.27	EC50	0.0537	nM	CHEMBL5832273
10.24	Ki	0.057	nM	CHEMBL4790662
10.22	Ki	0.06026	nM	CHEMBL4786067
10.22	Ki	0.06026	nM	CHEMBL4750444
10.22	Ki	0.06026	nM	CHEMBL4756041
10.21	Ki	0.06166	nM	CHEMBL4741857
10.21	Ki	0.061	nM	CHEMBL4741857

PubChem BioAssay actives

3390 with measured affinity, of 6100 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
1-[4-(3-methoxyphenyl)cyclohexyl]-4-pyridin-2-ylpiperazine	1234842: Agonist activity at human 5-HT1A receptor expressed in human HeLa cell membranes assessed as stimulation of [35S]GTPgammaS binding after 20 mins by liquid scintillation counting analysis	ki	<0.0001	uM
6-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-3-methyl-1,3-benzoxazol-2-one	1854986: Binding affinity to 5-HT1A receptor (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
2-[4-[4-(7-(111C)methoxynaphthalen-1-yl)piperazin-1-yl]butyl]-4-methyl-1,2,4-triazine-3,5-dione	259336: Agonistic activity at human 5HT1A in CHO cells by the inhibition of forskolin-stimulated cAMP accumulation	ec50	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(1H-indol-4-yloxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3,4-dichlorophenyl)-[4-fluoro-4-[[2-(3-fluorophenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3,4-dichlorophenyl)-[4-fluoro-4-[(2-phenoxyethylamino)methyl]piperidin-1-yl]methanone	1702243: Displacement of [3H]8-OH-DPAT from recombinant human 5HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by microbeta2 scintillation counting method	ki	<0.0001	uM
N-[3-[2-[[1-(3,4-dichlorobenzoyl)-4-fluoropiperidin-4-yl]methylamino]ethoxy]phenyl]acetamide	1675991: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay	ec50	<0.0001	uM
3-[2-[[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl]methylamino]ethoxy]benzamide	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
[4-[[2-(3-chlorophenoxy)ethylamino]methyl]-4-fluoropiperidin-1-yl]-(3,4-dichlorophenyl)methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
N-[3-[2-[[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl]methylamino]ethoxy]phenyl]acetamide	1675989: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay	ec50	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(2-methoxyphenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[(2-quinolin-8-yloxyethylamino)methyl]piperidin-1-yl]methanone	1675991: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay	ec50	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-[[2-(3-chlorophenoxy)ethylamino]methyl]-4-fluoropiperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-[3-(methylamino)phenoxy]ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3,4-dichlorophenyl)-[4-fluoro-4-[[2-(3-methoxyphenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-[[2-[(2,2-dimethyl-3H-1-benzofuran-7-yl)oxy]ethylamino]methyl]-4-fluoropiperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-[[2-(2-chlorophenoxy)ethylamino]methyl]-4-fluoropiperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-[[2-(2,3-dihydro-1H-indol-4-yloxy)ethylamino]methyl]-4-fluoropiperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(2-fluorophenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
(3,4-dichlorophenyl)-[4-fluoro-4-[(2-pyridin-2-yloxyethylamino)methyl]piperidin-1-yl]methanone	1702243: Displacement of [3H]8-OH-DPAT from recombinant human 5HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by microbeta2 scintillation counting method	ki	<0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(3-fluorophenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	<0.0001	uM
6-[2-[4-(2,7-dimethylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344709: Displacement of [3H]WAY-100635 from human 5HT1A receptor expressed in CHO cells	ki	0.0001	uM
(3aR,9bS)-3-propyl-1,2,3a,4,5,9b-hexahydrobenzo[e]indol-9-ol	3477: Binding affinity against [3H]8-OH-DPAT-labeled 5-hydroxytryptamine 1A receptor sites in bovine hippocampus	ki	0.0001	uM
4-fluoro-5-methoxy-3-(2-pyrrolidin-1-ylethyl)-1H-indole	3796: Binding affinity towards human 5-hydroxytryptamine 1A receptor was determined using [3H]8-OH-DPAT-as radioligand	ki	0.0001	uM
N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-(2-phenylmethoxyphenoxy)ethanamine	6435: Affinity constant on CHO cells expressing Human recombinant 5-hydroxytryptamine receptor 1A	ki	0.0001	uM
N-[2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]ethyl]-4-fluorobenzamide	1855028: Binding affinity to human 5-HT1A receptor expressed in CHO cells assessed as inhibition constant	ki	0.0001	uM
1-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-4-pyridin-2-ylpiperazine	3816: Binding affinity on human cloned 5-hydroxytryptamine 1A receptor transfected in human cell lines (He La)	ki	0.0001	uM
(6aR,9R)-N-[(2R,5S,8S,8aS)-8-benzyl-8a-hydroxy-2-methyl-5-(2-methylpropyl)-3,6-dioxo-7,8-dihydro-5H-[1,3]oxazolo[3,2-a]pyrazin-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	3925: Binding affinity against 5-hydroxytryptamine 1A human cloned receptors in HEK293 cells using [3H]8-OH-DPAT as radioligand	ki	0.0001	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510144: Displacement of [3H]-WAY100635 from human recombinant 5HT1A receptor expressed in CHO cells after 45 mins by scintillation counting	ki	0.0001	uM
3-[4-[4-[4-(4-oxofuro[3,2-c]pyridin-5-yl)phenyl]piperazin-1-yl]butyl]-1H-indole-5-carbonitrile	1780958: Inhibition of 5-HT1a (unknown origin)	ic50	0.0001	uM
(3S)-3-[cyclopropylmethyl-[3-(5-fluoro-1H-indol-3-yl)propyl]amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide	268272: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor expressed in CHO cells	ki	0.0001	uM
2-[4-[4-(3-methoxyphenyl)piperazin-1-yl]butyl]-4-methyl-1,2,4-triazine-3,5-dione	1854986: Binding affinity to 5-HT1A receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
Brexpiprazole	1517957: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor expressed in CHO-K1 cell membranes incubated for 60 mins by microbeta scintillation counting analysis	ki	0.0001	uM
2-[2-[[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl]methylamino]ethoxy]benzamide	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[(2-phenoxyethylamino)methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[(2-pyridin-2-yloxyethylamino)methyl]piperidin-1-yl]methanone	1702243: Displacement of [3H]8-OH-DPAT from recombinant human 5HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(3-methylphenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-[[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethylamino]methyl]-4-fluoropiperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(4-fluorophenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-[2-(methylamino)phenoxy]ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[2-(3-methoxyphenoxy)ethylamino]methyl]piperidin-1-yl]methanone	1675981: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method	ki	0.0001	uM
methyl 3-[4-[4-(9-amino-5,6,7,8-tetrahydroacridin-1-yl)piperazin-1-yl]butyl]-1H-indole-5-carboxylate	1495953: Agonist activity at human 5-HT1A receptor expressed in HEK293 cells after 60 mins by Eu-cAMP solution based ultra LANCE assay	ec50	0.0001	uM
8-[4-[4-(5-methoxy-1H-indol-3-yl)butyl]piperazin-1-yl]-1,2,3,4-tetrahydroacridin-9-amine	1495953: Agonist activity at human 5-HT1A receptor expressed in HEK293 cells after 60 mins by Eu-cAMP solution based ultra LANCE assay	ec50	0.0001	uM
2-[4-[4-(1,3-benzothiazol-4-yl)piperazin-1-yl]butyl]-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-one	1659259: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay	ec50	0.0001	uM
2-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butyl]-6-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-one	1659259: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay	ec50	0.0001	uM
2-[4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butyl]-6,8-dichloro-[1,2,4]triazolo[4,3-a]pyridin-3-one	1659259: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay	ec50	0.0001	uM
4-fluoro-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide	3839: In vitro inhibition of [3H]- 8-OH-DPAT binding to cloned cell line containing human 5-hydroxytryptamine 1A receptor by Panlabs assay	ki	0.0002	uM
2-(4-fluoro-5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine	3796: Binding affinity towards human 5-hydroxytryptamine 1A receptor was determined using [3H]8-OH-DPAT-as radioligand	ki	0.0002	uM
1-(2-methoxyphenyl)-4-[4-(3-methoxyphenyl)cyclohexyl]piperazine	3817: Binding affinity on human cloned 5-hydroxytryptamine 1A receptor transfected in human cell lines(He La)	ki	0.0002	uM
(3aR,9bS)-9-methoxy-3-prop-2-enyl-1,2,3a,4,5,9b-hexahydrobenzo[e]indole	3480: Binding affinity against 5-hydroxytryptamine 1A receptor from bovine hippocampus, used [3H]8-OH-DPAT as radioligand	ki	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
8-Hydroxy-2-(di-n-propylamino)tetralin	affects binding, increases activity, decreases reaction	5
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide	affects binding, decreases reaction, increases activity, decreases activity	3
Fluoxetine	decreases expression, decreases reaction, increases response to substance, affects response to substance	3
(2-(2’,6’-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane	affects activity, affects binding, decreases reaction	2
1,2-benzisothiazol-3(2H)-one, 2-(4-(4-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl)butyl)-, 1,1-dioxide	decreases activity, affects binding	2
Aripiprazole	affects activity, affects binding, increases activity	2
Cyclic AMP	affects binding, increases activity, decreases reaction, increases abundance	2
Estradiol	affects cotreatment, increases expression, affects binding, increases reaction, decreases expression	2
Colforsin	increases abundance, affects binding, increases activity, decreases reaction	2
Serotonin	affects binding, decreases reaction, increases activity	2
bisphenol A	decreases methylation	1
cannabidiolic acid	increases expression	1
VX-agent	increases expression	1
etoperidone	affects binding	1
arsenite	increases methylation	1
ipsapirone	affects binding, increases activity	1
5-carboxamidotryptamine	affects binding, increases activity	1
nefazodone	affects binding	1
BMY 7378	affects binding, increases activity	1
N,N-dipropylcarboxamidotryptamine	affects binding, increases activity	1
5-methylurapidil	affects binding, increases activity	1
1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine	decreases activity, affects binding	1
binospirone mesylate	affects binding, increases activity	1
sarizotan	affects binding, increases activity	1
N-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yloxy)ethyl)-3-(cyclopent-1-enyl)benzylamine	affects binding, increases activity	1
N-(4-(4-(3-aminocarbonyl-phenyl)-piperazin-1-yl)-butyl)-4-bromo-benzamide	affects binding	1
JB-788	increases activity, decreases reaction, increases abundance, affects binding	1
Lurasidone Hydrochloride	affects binding, increases activity	1
Resveratrol	affects cotreatment, decreases expression	1
Vortioxetine	affects binding, increases activity	1

ChEMBL screening assays

1750 unique, capped per target: 1235 binding, 504 functional, 10 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060606	Binding	Inhibition of 5HT	Discovery and optimization of novel purines as potent and selective CB2 agonists. — Bioorg Med Chem Lett
CHEMBL4413391	ADMET	Antagonist activity at serotonin receptor in human PBMC assessed as inhibition of PMA-stimulated superoxide anion generation at 10 uM preincubated for 1 hr followed by PMA-stimulation and measured after 30 mins by spectrophotometric method	Identification of a novel DGKα inhibitor for XLP-1 therapy by virtual screening. — Eur J Med Chem
CHEMBL619167	Functional	5-HT level in K+ induced 5-hydroxytryptamine release in guinea pig cortex.	New selective and potent 5-HT(1B/1D) antagonists: chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides. — J Med Chem

Cellosaurus cell lines

6 cell lines: 4 spontaneously immortalized cell line, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0SX	ACTOne HTR1A	Transformed cell line	Female
CVCL_H378	CHO-K1/5-HT1A/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV38	cAMP Hunter CHO-K1 HTR1A Gi	Spontaneously immortalized cell line	Female
CVCL_KX86	PathHunter CHO-K1 HTR1A beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZK39	GeneBLAzer 5TH1A-Galpha15-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_ZL06	Tango HTR1A-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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