HTR5A

Summary

HTR5A (5-hydroxytryptamine receptor 5A, HGNC:5300) is a protein-coding gene on chromosome 7q36.2, encoding 5-hydroxytryptamine receptor 5A (P47898). G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.

Source: NCBI Gene 3361 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 44 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024012

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5300
Approved symbol	HTR5A
Name	5-hydroxytryptamine receptor 5A
Location	7q36.2
Locus type	gene with protein product
Status	Approved
Aliases	5-HT5A
Ensembl gene	ENSG00000157219
Ensembl biotype	protein_coding
OMIM	601305
Entrez	3361

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000287907, ENST00000486819, ENST00000649716

RefSeq mRNA: 1 — MANE Select: NM_024012 NM_024012

CCDS: CCDS5936

Canonical transcript exons

ENST00000287907 — 2 exons

Exon	Start	End
ENSE00001031298	155070324	155071640
ENSE00003831873	155084155	155087392

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 86.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6765 / max 46.6123, expressed in 87 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82205	0.5548	80
82204	0.1217	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	86.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.06	gold quality
cerebellar cortex	UBERON:0002129	86.01	gold quality
cerebellum	UBERON:0002037	84.42	gold quality
prefrontal cortex	UBERON:0000451	82.33	gold quality
right frontal lobe	UBERON:0002810	80.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.33	gold quality
frontal cortex	UBERON:0001870	78.03	gold quality
anterior cingulate cortex	UBERON:0009835	77.47	gold quality
cingulate cortex	UBERON:0003027	77.36	gold quality
neocortex	UBERON:0001950	76.58	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.37	gold quality
cerebral cortex	UBERON:0000956	73.44	gold quality
secondary oocyte	CL:0000655	72.31	silver quality
hypothalamus	UBERON:0001898	71.26	gold quality
telencephalon	UBERON:0001893	71.02	gold quality
nucleus accumbens	UBERON:0001882	70.01	gold quality
brain	UBERON:0000955	69.85	gold quality
gingival epithelium	UBERON:0001949	69.77	gold quality
superior frontal gyrus	UBERON:0002661	68.83	gold quality
forebrain	UBERON:0001890	68.65	gold quality
caudate nucleus	UBERON:0001873	68.52	gold quality
putamen	UBERON:0001874	67.61	gold quality
gingiva	UBERON:0001828	67.35	gold quality
primary visual cortex	UBERON:0002436	67.25	gold quality
superficial temporal artery	UBERON:0001614	67.21	gold quality
postcentral gyrus	UBERON:0002581	67.14	gold quality
cartilage tissue	UBERON:0002418	66.45	gold quality
amygdala	UBERON:0001876	66.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2

miRNA regulators (miRDB)

130 targeting HTR5A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AR-3P	99.85	71.26	3889

Literature-anchored findings (GeneRIF, showing 9)

• N-glycosylation of the N6 residue is important for the membrane expression of this 5-HT5A neurotransmitter receptor; a requirement for receptor function. (PMID:17881091)
• In individuals in Brazil with the A/A variant of the -1438G/A polymorphism of the 2A receptor gene, the effect of cultural consonance in family life on depressive symptoms over a 2 year period was larger than those with the G/A or G/G variants. (PMID:18802937)
• Association of a SNP of HTR5A gene is a susceptibility factor to bipolar disease in Bulgarian population. (PMID:19328558)
• Childhood anxiousness did not mediate the effects of HTR2A and HTR5A on mood disorders. (PMID:19381154)
• Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels (PMID:20388841)
• Results suggest that TPH1 218A/C and HTR5A 12A/T polymorphisms cannot predict treatment response in major depression (PMID:24903772)
• results provide further supportive evidence of the effect of HTR1A and HTR5A on the etiology of schizophrenia and suggest that the selected genetic variations in HTR5A may be involved in impaired executive function. (PMID:27897266)
• 5-HT receptor agonist Valerenic Acid enhances the innate immunity signal and suppresses glioblastoma cell growth and invasion. (PMID:32549758)
• The receptor has been transiently expressed in Cos M6 cells and exhibits a pharmacological profile closely resembling the mouse and rat 5-HT5A receptors with high, specific binding for ergotamine and methiothepin. (PMID:7988681)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr5aa	ENSDARG00000038869
danio_rerio	htr5ab	ENSDARG00000068557
mus_musculus	Htr5a	ENSMUSG00000039106
rattus_norvegicus	Htr5a	ENSRNOG00000007066

Paralogs (8): HTR2A (ENSG00000102468), HTR1B (ENSG00000135312), HTR2B (ENSG00000135914), HTR2C (ENSG00000147246), HTR7 (ENSG00000148680), HTR6 (ENSG00000158748), HTR1E (ENSG00000168830), HTR1F (ENSG00000179097)

Protein

Protein identifiers

5-hydroxytryptamine receptor 5A — P47898 (reviewed: P47898)

Alternative names: Serotonin receptor 5A

All UniProt accessions (3): P47898, A0A3B3ISH0, A4D2N2

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen. Also functions as a receptor for ergot alkaloid derivatives and other 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. HTR5A 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.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_076917* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001397	5HT5A_rcpt	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (56 total): mutagenesis site 17, helix 13, topological domain 8, transmembrane region 7, turn 4, glycosylation site 2, chain 1, binding site 1, disulfide bond 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7UM5	ELECTRON MICROSCOPY	2.73
7UM7	ELECTRON MICROSCOPY	2.75
7UM6	ELECTRON MICROSCOPY	2.79
7UM4	X-RAY DIFFRACTION	2.8
7X5H	ELECTRON MICROSCOPY	3.1
9W6W	ELECTRON MICROSCOPY	3.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47898-F1	79.80	0.46

Antibody-complex structures (SAbDab): 5 — 7UM5, 7UM6, 7UM7, 7X5H, 9W6W

Functional residue map

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

Ligand- & substrate-binding residues (1): 121

Disulfide bonds (1): 114–192

Glycosylation sites (2): 6, 21

Mutagenesis-validated functional residues (17):

Position	Phenotype
121	abolished g(i)/(o)-coupled receptor activity.
142	does not affect g(i)/(o)-coupled receptor activity.
143	strongly decreased g(i)/(o)-coupled receptor activity.
147	does not affect g(i)/(o)-coupled receptor activity.
154	abolished g(i)/(o)-coupled receptor activity.
204	decreased g(i)/(o)-coupled receptor activity.
223	strongly decreased g(i)/(o)-coupled receptor activity.
226–227	strongly increased g(i)/(o)-coupled receptor activity.
226	strongly increased g(i)/(o)-coupled receptor activity.
227	increased g(i)/(o)-coupled receptor activity.
230	slightly decreased g(i)/(o)-coupled receptor activity.
282	strongly decreased g(i)/(o)-coupled receptor activity.
284	strongly increased g(i)/(o)-coupled receptor activity.
286	slightly decreased g(i)/(o)-coupled receptor activity.
287	abolished g(i)/(o)-coupled receptor activity.
305	increased g(i)/(o)-coupled receptor activity.
342	strongly decreased g(i)/(o)-coupled receptor activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-390666	Serotonin receptors
R-HSA-418594	G alpha (i) signalling events
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-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 170 (showing top): GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, GOBP_RESPONSE_TO_ESTRADIOL, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, IRF7_01, GOBP_HIPPOCAMPUS_DEVELOPMENT, GOBP_PALLIUM_DEVELOPMENT, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOBP_RESPONSE_TO_LIPID, GOBP_HEAD_DEVELOPMENT, GOBP_ADENYLATE_CYCLASE_INHIBITING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (9): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), chemical synaptic transmission (GO:0007268), hippocampus development (GO:0021766), response to estradiol (GO:0032355), signal transduction (GO:0007165), G protein-coupled serotonin receptor signaling pathway (GO:0098664)

GO Molecular Function (5): Gi/o-coupled serotonin receptor activity (GO:0001586), G protein-coupled serotonin receptor activity (GO:0004993), neurotransmitter receptor activity (GO:0030594), serotonin receptor activity (GO:0099589), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (5): plasma membrane (GO:0005886), dendrite (GO:0030425), perikaryon (GO:0043204), postsynaptic specialization membrane (GO:0099634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled serotonin receptor signaling pathway	2
G protein-coupled serotonin receptor activity	2
transmembrane signaling receptor activity	2
cellular anatomical structure	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
pallium development	1
limbic system development	1
anatomical structure development	1
response to lipid	1
response to oxygen-containing compound	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled amine receptor activity	1
serotonin binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
neuronal cell body	1
postsynaptic membrane	1
synaptic membrane	1
postsynaptic specialization	1

Protein interactions and networks

STRING

2096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR5A	ALDH18A1	P54886	762
HTR5A	HTR3A	P46098	723
HTR5A	HTR3B	O95264	655
HTR5A	GAST	P01350	649
HTR5A	SLC6A4	P31645	624
HTR5A	HTR3D	Q70Z44	564
HTR5A	WDR27	A2RRH5	545
HTR5A	HTR3C	Q8WXA8	532
HTR5A	HTR2B	P41595	523
HTR5A	STEEP1	Q9H5V9	521
HTR5A	HTR3E	A5X5Y0	500
HTR5A	HTR2A	P28223	492
HTR5A	SVOPL	Q8N434	489
HTR5A	HTR2C	P28335	475
HTR5A	PDPN	Q86YL7	466

IntAct

7 interactions, top by confidence:

A	B	Type	Score
	HTR5A	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR5A	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HTR5A	psi-mi:“MI:0915”(physical association)	0.400
HTR5A	BUD31	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): HTR5A (Two-hybrid), HTR5A (PCA)

ESM2 similar proteins: A0A678XMK4, A6QLE7, O17899, O42384, O42574, O70528, O77680, P04274, P07550, P0C5J4, P10608, P17124, P18762, P18901, P21728, P25102, P30728, P42288, P42289, P42290, P42291, P47898, P49285, P49288, P50130, P51046, P53452, P54833, P70585, P97288, Q09638, Q13639, Q15760, Q16950, Q16951, Q28044, Q28509, Q28997, Q4KWL2, Q61121

Diamond homologs: E7EM37, O01670, O02662, O02666, O02824, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O42574, O77621, O77680, O77700, O77713, O77715, O77721, O77723, O77830, P04274, P07550, P07700, P10608, P11615, P13945, P15823, P17124, P18090, P18130, P18762, P18841, P18901, P21728, P21918, P23944, P25021, P25100, P25102

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
serotonin	“up-regulates activity”	HTR5A	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

496 predictions. Top by Δscore:

Variant	Effect	Δscore
7:155071641:G:GA	donor_loss	1.0000
7:155071601:G:GT	donor_gain	0.9900
7:155071637:GGAG:G	donor_gain	0.9900
7:155071638:GAG:G	donor_gain	0.9900
7:155071638:GAGG:G	donor_gain	0.9900
7:155071641:G:GG	donor_gain	0.9900
7:155084150:TACA:T	acceptor_loss	0.9900
7:155084152:CA:C	acceptor_loss	0.9900
7:155084153:A:AC	acceptor_loss	0.9900
7:155084153:A:AG	acceptor_gain	0.9900
7:155084153:AGGT:A	acceptor_gain	0.9900
7:155084154:G:GT	acceptor_gain	0.9900
7:155084154:GGT:G	acceptor_gain	0.9900
7:155084154:GGTG:G	acceptor_gain	0.9900
7:155071639:AGGTG:A	donor_gain	0.9800
7:155082529:TCTC:T	donor_gain	0.9800
7:155084151:A:AG	acceptor_gain	0.9800
7:155084153:AG:A	acceptor_gain	0.9800
7:155084154:GG:G	acceptor_gain	0.9800
7:155084154:GGTGA:G	acceptor_gain	0.9800
7:155075443:A:G	donor_gain	0.9700
7:155082535:G:GG	donor_gain	0.9700
7:155075581:A:T	donor_gain	0.9600
7:155084152:C:G	acceptor_gain	0.9600
7:155082428:G:GG	donor_gain	0.9500
7:155083489:G:GT	donor_gain	0.9500
7:155081163:G:GC	acceptor_gain	0.9400
7:155082427:A:AG	donor_gain	0.9400
7:155084150:TACAG:T	acceptor_gain	0.9400
7:155084153:AGGTG:A	acceptor_gain	0.9300

AlphaMissense

2321 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:155071281:A:C	S128R	0.997
7:155071283:C:A	S128R	0.997
7:155071283:C:G	S128R	0.997
7:155071524:T:C	F209L	0.997
7:155071526:C:A	F209L	0.997
7:155071526:C:G	F209L	0.997
7:155084293:T:C	F294L	0.996
7:155084295:C:A	F294L	0.996
7:155084295:C:G	F294L	0.996
7:155071220:G:C	W107C	0.995
7:155071220:G:T	W107C	0.995
7:155071395:T:A	W166R	0.993
7:155071395:T:C	W166R	0.993
7:155084314:T:C	F301L	0.993
7:155084316:C:A	F301L	0.993
7:155084316:C:G	F301L	0.993
7:155084386:T:A	W325R	0.993
7:155084386:T:C	W325R	0.993
7:155071156:A:T	D86V	0.991
7:155084305:T:A	W298R	0.991
7:155084305:T:C	W298R	0.991
7:155084312:C:A	P300H	0.991
7:155084312:C:G	P300R	0.991
7:155084317:T:C	F302L	0.991
7:155084319:T:A	F302L	0.991
7:155084319:T:G	F302L	0.991
7:155071157:T:A	D86E	0.990
7:155071157:T:G	D86E	0.990
7:155071303:T:A	I135K	0.990
7:155071315:G:C	R139P	0.990

dbSNP variants (sampled 300 via entrez): RS1000029446 (7:155079118 C>A), RS1000062044 (7:155077913 C>G,T), RS1000270922 (7:155076048 C>G), RS1000358096 (7:155086432 C>T), RS1000410778 (7:155074194 G>A), RS1000683003 (7:155082154 C>T), RS1000688929 (7:155070337 C>A,T), RS1000745053 (7:155075373 A>G), RS1000758177 (7:155069185 T>C), RS1001012077 (7:155077219 A>T), RS1001092374 (7:155071721 C>A,T), RS1001375800 (7:155072498 C>G,T), RS1001424671 (7:155072834 C>T), RS1001517731 (7:155085080 T>G), RS1001854554 (7:155086298 G>A,T)

Disease associations

OMIM: gene MIM:601305 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002111_4	Personality dimensions	7.000000e-06
GCST002397_2	Bladder cancer (smoking interaction)	2.000000e-06
GCST004524_3	Energy expenditure (24h)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096904 (PROTEIN FAMILY), CHEMBL3426 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

44 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 438,752 (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
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4	5,428
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,220
CHEMBL126224	IPRINDOLE	4	4,398
CHEMBL128	SUMATRIPTAN	4	28,367
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1516474	TEGASEROD MALEATE	4	1,823
CHEMBL1558	PRAZOSIN HYDROCHLORIDE	4	11,347
CHEMBL1628227	DOXEPIN	4	28,171
CHEMBL2024517	CARIPRAZINE HYDROCHLORIDE	4	277
CHEMBL2105760	BREXPIPRAZOLE	4	1,755
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL442	ERGOTAMINE	4	19,697
CHEMBL490	PAROXETINE	4	46,410
CHEMBL500	PINDOLOL	4	28,693
CHEMBL51	KETANSERIN	4	20,018
CHEMBL535	SUNITINIB	4
CHEMBL54	HALOPERIDOL	4
CHEMBL564	PROMAZINE	4
CHEMBL657	DIPHENHYDRAMINE	4
CHEMBL71	CHLORPROMAZINE	4
CHEMBL715	OLANZAPINE	4
CHEMBL76370	TEGASEROD	4
CHEMBL831	LOXAPINE	4
CHEMBL85	RISPERIDONE	4
CHEMBL896	HYDROXYZINE	4

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1440451	HTR5A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — 5-Hydroxytryptamine receptors

Most potent curated ligand interactions (24 total), top 24:

Ligand	Action	Affinity	Parameter
[125I]LSD	Full agonist	9.7	pKd
methiothepin	Antagonist	8.9	pKi
ergotamine	Antagonist	8.7	pKi
[3H]5-CT	Full agonist	8.6	pKd
SB 699551	Antagonist	8.2	pKi
5-CT	Full agonist	7.7	pKi
ritanserin	Antagonist	7.6	pKi
methysergide	Antagonist	7.0	pKi
5-hydroxytryptamine	Full agonist	6.9	pKi
vortioxetine	Antagonist	6.66	pKi
clozapine	Antagonist	6.5	pKi
metergoline	Antagonist	6.2	pKi
donitriptan	Full agonist	6.1	pKi
bufotenine	Antagonist	6.0	pKi
RU 24969	Full agonist	6.0	pKi
lysergic acid	Full agonist	5.7	pKi
8-OH-DPAT	Full agonist	5.7	pKi
TFMPP	Full agonist	5.6	pKi
yohimbine	Antagonist	5.3	pKi
EMDT	Full agonist	5.3	pKi
sumatriptan	Full agonist	5.3	pKi
MPDT	Antagonist	5.3	pKi
(-)-propranolol	Antagonist	5.1	pKi
ketanserin	Antagonist	4.7	pKi

Binding affinities (BindingDB)

50 measured of 74 human assays (77 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_104911	KI	0.1 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
N-(diaminomethylidene)-5-fluoro-8-(2,4,6-trifluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	0.68 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-8-(2,6-difluorophenyl)-5-fluorospiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-2-carboxamide	KI	0.75 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-8-(2,4-difluorophenyl)-5-fluorospiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-2-carboxamide	KI	0.85 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-5-fluoro-8-(2,4,6-trifluorophenyl)spiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-2-carboxamide	KI	0.88 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-5-fluoro-8-(2-fluorophenyl)spiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-2-carboxamide	KI	0.95 nM	US-8962612: Tetrahydroisoquinoline derivative
5-chloro-N-(diaminomethylidene)-8-(2,4,6-trifluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	1.1 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-8-(2,6-difluorophenyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	1.1 nM	US-8962612: Tetrahydroisoquinoline derivative
4-chloro-N-(diaminomethylidene)-1-(2,6-difluorophenyl)isoquinoline-7-carboxamide	KI	1.2 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
3-chloro-N-(diaminomethylidene)-4-(2,4-difluorophenyl)quinoline-6-carboxamide	KI	1.3 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-4-methyl-1-(2,4,6-trifluorophenyl)isoquinoline-7-carboxamide	KI	1.3 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-5-fluoro-8-(2,4,5-trifluorophenyl)spiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-2-carboxamide	KI	1.3 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-1-(2,6-difluorophenyl)-4-fluoroisoquinoline-7-carboxamide	KI	1.4 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
1-(2-chloro-6-fluorophenyl)-N-(diaminomethylidene)-4-fluoroisoquinoline-7-carboxamide	KI	1.6 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-8-(2,6-difluorophenyl)-5-fluoro-4-methyl-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	1.6 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-1-(2-fluorophenyl)-4-methylisoquinoline-7-carboxamide	KI	1.8 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-1-(2,6-difluorophenyl)-4-methylisoquinoline-7-carboxamide	KI	1.9 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-8-(3,5-dichloro-2-pyridinyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	1.9 nM	US-8962612: Tetrahydroisoquinoline derivative
4-chloro-N-(diaminomethylidene)-1-(2,4-difluorophenyl)isoquinoline-7-carboxamide	KI	2.3 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
5-chloro-N-(diaminomethylidene)-8-(3,5-difluoro-4-pyridinyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	2.5 nM	US-8962612: Tetrahydroisoquinoline derivative
5-chloro-N-(diaminomethylidene)-8-(2,4-difluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	2.7 nM	US-8962612: Tetrahydroisoquinoline derivative
8-cyclopropyl-N-(diaminomethylidene)-5-fluorospiro[1,3-dihydroisoquinoline-4,1’-cyclopropane]-2-carboxamide	KI	2.7 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-4-fluoro-1-(2-fluorophenyl)isoquinoline-7-carboxamide	KI	3.3 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
1-(2-chlorophenyl)-N-(diaminomethylidene)-4-fluoroisoquinoline-7-carboxamide	KI	3.4 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-8-(2,4,5-trifluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	3.6 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-2,3-dimethyl-4-(2,4,6-trifluorophenyl)quinoline-6-carboxamide	KI	3.7 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-5-fluoro-8-(2,4,5-trifluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	3.7 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-8-(3,5-difluoro-2-pyridinyl)-5-methyl-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	3.9 nM	US-8962612: Tetrahydroisoquinoline derivative
1-(2-chloro-4-fluorophenyl)-N-(diaminomethylidene)-4-fluoroisoquinoline-7-carboxamide	KI	4.1 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-8-(3,5-difluoro-2-pyridinyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	4.2 nM	US-8962612: Tetrahydroisoquinoline derivative
8-(5-chloro-3-fluoro-2-pyridinyl)-N-(diaminomethylidene)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	4.3 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-4-(difluoromethyl)-1-(2,6-difluorophenyl)isoquinoline-7-carboxamide	KI	4.6 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
1-(3-chloro-5-fluoro-4-pyridinyl)-N-(diaminomethylidene)-4-fluoroisoquinoline-7-carboxamide	KI	4.7 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-1-(3,5-difluoro-4-pyridinyl)-4-fluoroisoquinoline-7-carboxamide	KI	5.3 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
1-(3-chloro-5-fluoro-2-pyridinyl)-N-(diaminomethylidene)-4-fluoroisoquinoline-7-carboxamide	KI	6.2 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
5-chloro-N-(diaminomethylidene)-8-(2,4-difluorophenyl)-4-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	6.6 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-8-(3,5-difluoro-2-pyridinyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxamide	KI	6.9 nM	US-8962612: Tetrahydroisoquinoline derivative
N-(diaminomethylidene)-4-fluoro-1-(2-fluoro-6-methoxyphenyl)isoquinoline-7-carboxamide	KI	7.1 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
N-(diaminomethylidene)-2-methyl-4-(2,4,6-trifluorophenyl)quinoline-6-carboxamide	KI	13 nM	US-8853242: Nitrogenous-ring acylguanidine derivative
Fluorocarazolol,(S)	KI	34 nM
SMR001230745	KI	63.1 nM
S32504	KI	257 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one	KI	288 nM
RS-127445	KI	501 nM
SR 147778	KI	1000 nM
SL65.0155	KI	1020 nM
2-(3-(5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-8-yl)-4-hydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	IC50	1630 nM
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one	IC50	72800 nM

ChEMBL bioactivities

446 potent at pChembl≥5 of 463 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	Kd	0.1585	nM	CHEMBL323208
9.17	Ki	0.68	nM	CHEMBL3654198
9.12	Ki	0.75	nM	CHEMBL3654206
9.11	Ki	0.78	nM	CHEMBL282199
9.07	Ki	0.85	nM	CHEMBL3654212
9.06	Ki	0.88	nM	CHEMBL3654208
9.02	Ki	0.95	nM	CHEMBL3654214
9.00	IC50	1	nM	CHEMBL1210154
9.00	Ki	1	nM	METITEPINE
8.96	Ki	1.1	nM	CHEMBL3654197
8.96	Ki	1.1	nM	CHEMBL3654199
8.96	IC50	1.1	nM	IMIPRAMINE
8.96	Ki	1.1	nM	IMIPRAMINE
8.92	Ki	1.2	nM	CHEMBL3644535
8.89	Ki	1.3	nM	CHEMBL3644525
8.89	Ki	1.3	nM	CHEMBL3644530
8.89	Ki	1.3	nM	CHEMBL3654210
8.85	Ki	1.4	nM	CHEMBL3644528
8.82	Ki	1.5	nM	CHEMBL5093295
8.80	Ki	1.6	nM	CHEMBL3644527
8.80	Ki	1.6	nM	CHEMBL3654207
8.80	Ki	1.6	nM	CHEMBL404372
8.74	Ki	1.8	nM	CHEMBL3644540
8.74	Ki	1.8	nM	CHEMBL256694
8.72	Ki	1.9	nM	CHEMBL3644537
8.72	Ki	1.9	nM	CHEMBL3654205
8.70	Ki	2	nM	CHEMBL273170
8.64	Ki	2.3	nM	CHEMBL3644541
8.62	Ki	2.4	nM	CHEMBL5079273
8.60	Ki	2.5	nM	CHEMBL3654204
8.57	Ki	2.7	nM	CHEMBL3654200
8.57	Ki	2.7	nM	CHEMBL3654209
8.52	Kd	3.02	nM	CHEMBL270177
8.52	Ki	3	nM	CHEMBL24462
8.51	Ki	3.1	nM	CHEMBL5075486
8.50	Kd	3.162	nM	CHEMBL270177
8.48	Ki	3.3	nM	CHEMBL3644533
8.47	Ki	3.4	nM	CHEMBL3644534
8.44	Ki	3.6	nM	CHEMBL3654196
8.43	Ki	3.7	nM	CHEMBL3644526
8.43	Ki	3.7	nM	CHEMBL3654211
8.41	Ki	3.9	nM	CHEMBL3654203
8.40	Ki	4	nM	CHEMBL5089996
8.39	Ki	4.1	nM	CHEMBL3644529
8.38	Ki	4.2	nM	CHEMBL3654213
8.37	Ki	4.3	nM	CHEMBL3654195
8.34	Ki	4.6	nM	CHEMBL3644539
8.33	Ki	4.7	nM	CHEMBL3644536
8.33	Ki	4.7	nM	CHEMBL401745
8.30	Ki	5.012	nM	CHEMBL361256

PubChem BioAssay actives

357 with measured affinity, of 1089 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
(4-oxo-2-azatricyclo[3.3.1.02,7]nonan-8-yl) 1H-indole-3-carboxylate	200911: Potency was evaluated on rabbit heart serotonergic receptors	kd	0.0002	uM
3-[(2R)-2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidin-1-yl]sulfonylphenol	1769149: Binding affinity to 5HT5A receptor (unknown origin)	ki	0.0008	uM
1-methyl-4-(3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine	6479: Binding affinity towards human 5-hydroxytryptamine 5A receptor	ki	0.0010	uM
[(E)-1-(3-thiophen-2-ylphenyl)ethylideneamino] N-phenylcarbamate	493596: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in CHO cells	ic50	0.0010	uM
Imipramine	2198785: Inhibition of 5HT receptor (unknown origin)	ic50	0.0011	uM
N-[(5-chloroquinolin-8-yl)methyl]-1-[(7S)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-7-yl]methanamine	1826348: Displacement of [3H]-5-CT from human 5-HT5A receptor at 32 uM incubated for 2 hr by radioligand binding assay	ki	0.0015	uM
(4S)-5-chloro-4-methyl-1,4-dihydroquinazolin-2-amine	316378: Binding affinity to human 5HT5A receptor	ki	0.0016	uM
(4S)-5,6-dichloro-N-(2,2-difluoroethyl)-4-methyl-3,4-dihydro-1H-quinazolin-2-imine	316378: Binding affinity to human 5HT5A receptor	ki	0.0018	uM
5,6-dichloro-4-methyl-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0020	uM
N-[(5-chloroquinolin-8-yl)methyl]-2-pyridin-3-ylethanamine	1826349: Displacement of [3H]-5-CT from human 5-HT5A receptor at 1 uM incubated for 2 hr by radioligand binding assay	ki	0.0024	uM
5-chloro-4-methyl-1,4-dihydroquinazolin-2-amine	315637: Antagonist activity at human recombinant 5HT5A receptor expressed in HEK293-EBNA cells by [35S]GTP-gamma-S binding assay	kd	0.0030	uM
8-piperazin-1-ylnaphthalen-2-ol	6499: Binding affinity for rodent 5-hydroxytryptamine 5A receptor	ki	0.0030	uM
N-[(5-chloroquinolin-8-yl)methyl]-1-[(3S)-1,1-dioxothian-3-yl]methanamine	1826348: Displacement of [3H]-5-CT from human 5-HT5A receptor at 32 uM incubated for 2 hr by radioligand binding assay	ki	0.0031	uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0031	uM
(4S)-4-[[(5-chloroquinolin-8-yl)methylamino]methyl]-1-methylpiperidin-2-one	1826348: Displacement of [3H]-5-CT from human 5-HT5A receptor at 32 uM incubated for 2 hr by radioligand binding assay	ki	0.0040	uM
6-chloro-8-methoxy-4,5-dimethyl-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0047	uM
1-carbazol-9-yl-5-[4-(2-methoxyphenyl)piperazin-1-yl]pentan-1-one;hydrochloride	1278638: Binding affinity to recombinant 5-HT5 receptor (unknown origin) after 1.5 hrs by radioligand displacement assay	ki	0.0050	uM
(E)-N-[2-(dimethylamino)ethyl]-3-phenyl-N-[[4-[5-[(2-phenylethylamino)methyl]-2-pyridinyl]phenyl]methyl]prop-2-enamide	239953: Binding affinity towards human 5-hydroxytryptamine receptor 5A expressed in CHO cells using the radioligand [3H]LSD	ki	0.0050	uM
5,6-dichloro-N-(2,2-difluoroethyl)-4-methyl-3,4-dihydro-1H-quinazolin-2-imine	316378: Binding affinity to human 5HT5A receptor	ki	0.0057	uM
5-chloro-N-(2,2-difluoroethyl)-4-methyl-3,4-dihydro-1H-quinazolin-2-imine	316378: Binding affinity to human 5HT5A receptor	ki	0.0063	uM
5,6-dichloro-N,4-dimethyl-3,4-dihydro-1H-quinazolin-2-imine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0063	uM
8-methoxy-4-methyl-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0063	uM
3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[[4-[4-[(2-phenylethylamino)methyl]phenyl]phenyl]methyl]propanamide;bis(2,2,2-trifluoroacetic acid)	239953: Binding affinity towards human 5-hydroxytryptamine receptor 5A expressed in CHO cells using the radioligand [3H]LSD	ki	0.0063	uM
5,8-dichloro-4-methyl-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0065	uM
N-[(5-chloroquinolin-8-yl)methyl]-2-[(3R)-oxolan-3-yl]ethanamine	1826348: Displacement of [3H]-5-CT from human 5-HT5A receptor at 32 uM incubated for 2 hr by radioligand binding assay	ki	0.0067	uM
(4R)-4-[[(5-chloroquinolin-8-yl)methylamino]methyl]-1-cyclopropylpyrrolidin-2-one	1826348: Displacement of [3H]-5-CT from human 5-HT5A receptor at 32 uM incubated for 2 hr by radioligand binding assay	ki	0.0067	uM
(4S)-5-chloro-N-(2,2-difluoroethyl)-4-methyl-3,4-dihydro-1H-quinazolin-2-imine	316378: Binding affinity to human 5HT5A receptor	ki	0.0068	uM
5-chloro-N,4-dimethyl-3,4-dihydro-1H-quinazolin-2-imine	315637: Antagonist activity at human recombinant 5HT5A receptor expressed in HEK293-EBNA cells by [35S]GTP-gamma-S binding assay	kd	0.0074	uM
(6aR,9R)-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0090	uM
(6aR,9R)-5-bromo-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	6499: Binding affinity for rodent 5-hydroxytryptamine 5A receptor	ki	0.0100	uM
(6aR,9R)-N,N-diethyl-5-iodo-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	6499: Binding affinity for rodent 5-hydroxytryptamine 5A receptor	ki	0.0100	uM
4-methyl-8-propan-2-yloxy-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0100	uM
2-N-[(2-imidazol-1-ylphenyl)methyl]-4-N,4-N,5-trimethylpyrimidine-2,4-diamine	1826327: Displacement of [3H]-5-CT from human 5-HT5A receptor at 100 uM incubated for 2 hr by radioligand binding assay	ki	0.0120	uM
4-[(5-chloroquinolin-8-yl)methylamino]-N-cyclopropylbutanamide	1826327: Displacement of [3H]-5-CT from human 5-HT5A receptor at 100 uM incubated for 2 hr by radioligand binding assay	ki	0.0120	uM
1-phenyl-4-[2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)ethylamino]cyclohexane-1-carbonitrile	1826327: Displacement of [3H]-5-CT from human 5-HT5A receptor at 100 uM incubated for 2 hr by radioligand binding assay	ki	0.0120	uM
(2S)-1-(4-methylpyrazol-1-yl)-N-[[3-(pyridin-2-ylmethoxy)phenyl]methyl]propan-2-amine	1826327: Displacement of [3H]-5-CT from human 5-HT5A receptor at 100 uM incubated for 2 hr by radioligand binding assay	ki	0.0120	uM
(2R)-1-(7-tert-butyl-3,4-dihydro-1H-isoquinolin-2-yl)-3-(oxan-4-yloxy)propan-2-ol	1826327: Displacement of [3H]-5-CT from human 5-HT5A receptor at 100 uM incubated for 2 hr by radioligand binding assay	ki	0.0120	uM
3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[[4-[5-[(2-phenylethylamino)methyl]-2-pyridinyl]phenyl]methyl]propanamide	239953: Binding affinity towards human 5-hydroxytryptamine receptor 5A expressed in CHO cells using the radioligand [3H]LSD	ki	0.0126	uM
[(6aR)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[(2R,4R)-2,4-dimethylazetidin-1-yl]methanone	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0127	uM
2-[3-(4-fluorophenoxy)propyl]-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole	6499: Binding affinity for rodent 5-hydroxytryptamine 5A receptor	ki	0.0130	uM
[(2R,4R)-2,4-dimethylazetidin-1-yl]-[(9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methanone	6502: Binding affinities towards 5-hydroxytryptamine 5A receptor	ki	0.0130	uM
Ergotamine	619747: Displacement of [3H]LSD from 5-HT5A receptor after 1.5 hrs by scintillation counting	ki	0.0140	uM
[(2S,4R)-2,4-dimethylazetidin-1-yl]-[(9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methanone	6501: Binding affinities against 5-hydroxytryptamine 5A receptor	ki	0.0160	uM
[(6aR)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[(2S,4R)-2,4-dimethylazetidin-1-yl]methanone	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0164	uM
3-(2-aminoethyl)-1H-indole-5-carboxamide	6479: Binding affinity towards human 5-hydroxytryptamine 5A receptor	ki	0.0200	uM
N-(2,2-difluoroethyl)-4-methyl-8-propan-2-yloxy-3,4-dihydro-1H-quinazolin-2-imine	316378: Binding affinity to human 5HT5A receptor	ki	0.0222	uM
6-chloro-N-(2,2-difluoroethyl)-5-methoxy-4-methyl-3,4-dihydro-1H-quinazolin-2-imine	316378: Binding affinity to human 5HT5A receptor	ki	0.0222	uM
6-chloro-5-methoxy-4-methyl-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0229	uM
4-ethyl-1,4-dihydroquinazolin-2-amine	315623: Displacement of [3H]LSD from human recombinant 5HT5A receptor expressed in HEK293-EBNA cells	ki	0.0240	uM
(E)-N-[2-(dimethylamino)ethyl]-3-phenyl-N-[[6-[4-[(2-phenylethylamino)methyl]phenyl]-3-pyridinyl]methyl]prop-2-enamide	239953: Binding affinity towards human 5-hydroxytryptamine receptor 5A expressed in CHO cells using the radioligand [3H]LSD	ki	0.0251	uM

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression	1
bisphenol S	increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Benzene	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lead	affects expression	1
Phthalic Acids	increases methylation	1
Rotenone	decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

327 unique, capped per target: 294 binding, 29 functional, 4 admet

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

2 cell lines: 1 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV41	cAMP Hunter CHO-K1 HTR5A Gi	Spontaneously immortalized cell line	Female
CVCL_LA62	PathHunter U2OS HTR5A beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer