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HTR3E

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Summary

HTR3E (5-hydroxytryptamine receptor 3E, HGNC:24005) is a protein-coding gene on chromosome 3q27.1, encoding 5-hydroxytryptamine receptor 3E (A5X5Y0). Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.

This locus encodes a 5-hydroxytryptamine (serotonin) receptor subunit. The encoded protein, subunit E, may play a role in neurotransmission in myenteric neurons. Genes encoding subunits C, D and E form a cluster on chromosome 3. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 285242 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 82 total
  • Druggable target: yes — 19 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001256613

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24005
Approved symbolHTR3E
Name5-hydroxytryptamine receptor 3E
Location3q27.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000186038
Ensembl biotypeprotein_coding
OMIM610123
Entrez285242

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000335304, ENST00000415389, ENST00000425359, ENST00000431041, ENST00000436361, ENST00000440596

RefSeq mRNA: 5 — MANE Select: NM_001256613 NM_001256613, NM_001256614, NM_182589, NM_198313, NM_198314

CCDS: CCDS3251, CCDS58868, CCDS58869, CCDS58870, CCDS58871

Canonical transcript exons

ENST00000415389 — 9 exons

ExonStartEnd
ENSE00001338211184105765184105969
ENSE00001338213184105267184105427
ENSE00001338216184104182184104291
ENSE00001338217184101485184101529
ENSE00001338218184106464184106995
ENSE00001881031184097064184097596
ENSE00002455540184106128184106343
ENSE00002502836184104787184104956
ENSE00003546965184100485184100651

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 73.20.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of transverse colonUBERON:000499173.20gold quality
duodenumUBERON:000211460.52gold quality
placentaUBERON:000198753.80gold quality
transverse colonUBERON:000115751.24gold quality
small intestineUBERON:000210848.56gold quality
small intestine Peyer’s patchUBERON:000345447.78gold quality
intestineUBERON:000016042.59gold quality
colonic epitheliumUBERON:000039741.64gold quality
colonUBERON:000115540.44gold quality
sural nerveUBERON:001548839.96gold quality
rectumUBERON:000105239.73silver quality
right lungUBERON:000216738.53silver quality
skeletal muscle tissueUBERON:000113437.26gold quality
prefrontal cortexUBERON:000045136.86gold quality
hindlimb stylopod muscleUBERON:000425236.65silver quality
ventricular zoneUBERON:000305336.48gold quality
cortical plateUBERON:000534336.47gold quality
granulocyteCL:000009436.23gold quality
bone marrow cellCL:000209236.16gold quality
lymph nodeUBERON:000002936.03gold quality
ganglionic eminenceUBERON:000402335.49gold quality
calcaneal tendonUBERON:000370135.38gold quality
corpus callosumUBERON:000233634.76gold quality
muscle tissueUBERON:000238533.91gold quality
vermiform appendixUBERON:000115433.25silver quality
bone marrowUBERON:000237132.96gold quality
frontal cortexUBERON:000187032.59gold quality
liverUBERON:000210731.83gold quality
leukocyteCL:000073831.62silver quality
monocyteCL:000057631.42silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-MTAB-8410yes3.81
E-ANND-3no2.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting HTR3E, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6857-5P99.8765.32985
HSA-MIR-202-3P99.8471.411290
HSA-MIR-4802-3P99.7270.131273
HSA-MIR-3158-5P99.6567.511763
HSA-MIR-671-5P99.5267.111277
HSA-MIR-444199.4966.563216
HSA-MIR-361299.4566.021333
HSA-MIR-65099.4565.771309
HSA-MIR-6513-5P99.4367.811071
HSA-MIR-427099.0266.261987
HSA-MIR-92299.0267.231838
HSA-MIR-3619-5P99.0068.872308
HSA-MIR-214-3P98.7168.122128
HSA-MIR-76198.7168.072051
HSA-MIR-6754-5P98.6065.541627
HSA-MIR-6878-5P98.4967.912142
HSA-MIR-444398.0266.251928
HSA-MIR-450A-2-3P97.9167.561459
HSA-MIR-3664-3P97.8567.621452
HSA-MIR-510-5P97.6665.82916
HSA-MIR-4715-5P97.6267.47506
HSA-MIR-431497.5067.301369
HSA-MIR-320197.1665.421044
HSA-MIR-479196.5167.76659
HSA-MIR-316996.4067.58698
HSA-MIR-426496.3564.761480
HSA-MIR-31-3P95.1769.82575
HSA-MIR-4757-3P88.8663.5551

Literature-anchored findings (GeneRIF, showing 7)

  • Data show that 5-HT3 receptors locat in the nucleus tractus silitarius contribute to stress-induced suppression of the baroreflex. (PMID:18573276)
  • MicroRNA-510 target site of the 3’UTR of HTR3A and HTR3E are associated with the irritable bowel syndrome with diarrhea. (PMID:18614545)
  • The binding site for miR-510 is solely located in the 3’ UTR of the HTR3E gene. No predicted binding site for miR-510 exists in the 3’ UTR of HTR3A. (PMID:18614545)
  • Six functional and coding variants of the subunit genes HTR3A, HTR3B as well as the novel HTR3C, HTR3D, and HTR3E subunits in the response to haloperidol or risperidone, were assessed. (PMID:19794330)
  • This study provides additional evidence for a role of the serotonergic system and the 5-HT3 receptor in schizophrenia (PMID:20356718)
  • Data show that 5-HT3C, 5-HT3D, and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric neurons, and that 5-HT3A and 5-HT3D were expressed in submucosal plexus of the human large intestine. (PMID:21192076)
  • the HTR3E remained significant after correction for the number of variants investigated. (PMID:23928294)

Cross-species orthologs

0 orthologs

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3D (ENSG00000186090)

Protein

Protein identifiers

5-hydroxytryptamine receptor 3E — A5X5Y0 (reviewed: A5X5Y0)

Alternative names: Serotonin receptor 3E

All UniProt accessions (2): A5X5Y0, C9J420

UniProt curated annotations — full annotation on UniProt →

Function. Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.

Subunit / interactions. Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Tissue specificity. Expressed in adult colon and intestine.

Domain organisation. The HA-stretch region of HTR3E seems to confer increased conductance to HTR3A/HTR3E heteropentamers compared to that of HTR3A homopentamers.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3E sub-subfamily.

Isoforms (5)

UniProt IDNamesCanonical?
A5X5Y0-11yes
A5X5Y0-22, 5-HT3c1
A5X5Y0-33
A5X5Y0-44, 5-HT3c1 long
A5X5Y0-65, HTR3E_V3

RefSeq proteins (5): NP_001243542, NP_001243543, NP_872395, NP_938055, NP_938056 (=MANE)

Domains & families (InterPro)

IDNameType
IPR006029Neurotrans-gated_channel_TMDomain
IPR006201Neur_channelFamily
IPR006202Neur_chan_lig-bdDomain
IPR018000Neurotransmitter_ion_chnl_CSConserved_site
IPR036719Neuro-gated_channel_TM_sfHomologous_superfamily
IPR036734Neur_chan_lig-bd_sfHomologous_superfamily
IPR038050Neuro_actylchol_recHomologous_superfamily
IPR049944LGIC_TM_5-HT3Domain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 3 shown:

  • K(+)(in) = K(+)(out) (RHEA:29463)
  • Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
  • Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (20 total): topological domain 5, transmembrane region 4, splice variant 3, sequence variant 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-A5X5Y0-F181.330.56

Functional residue map

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

Disulfide bonds (1): 162–176

Glycosylation sites (1): 175

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-112314Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315Transmission across Chemical Synapses
R-HSA-112316Neuronal System

MSigDB gene sets: 68 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOCC_NEURON_PROJECTION, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE

GO Biological Process (9): serotonin receptor signaling pathway (GO:0007210), chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), obsolete inorganic cation transmembrane transport (GO:0098662), serotonin-gated cation-selective signaling pathway (GO:0140227), monoatomic ion transport (GO:0006811), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (7): excitatory extracellular ligand-gated monoatomic ion channel activity (GO:0005231), serotonin-gated monoatomic cation channel activity (GO:0022850), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), transmembrane transporter complex (GO:1902495), serotonin-activated cation-selective channel complex (GO:1904602), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Transmission across Chemical Synapses1
Neuronal System1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
serotonin receptor activity2
serotonin receptor signaling pathway2
regulation of postsynaptic membrane potential2
transmitter-gated monoatomic ion channel activity2
signal transduction1
cellular response to dopamine1
anterograde trans-synaptic signaling1
monoatomic ion transport1
transmembrane transport1
monoatomic ion transmembrane transport1
regulation of biological quality1
serotonin-gated monoatomic cation channel activity1
ligand-gated ion channel signaling pathway1
transport1
regulation of membrane potential1
chemical synaptic transmission, postsynaptic1
extracellular ligand-gated monoatomic ion channel activity1
excitatory postsynaptic potential1
ligand-gated monoatomic cation channel activity1
signaling receptor activity1
monoatomic ion transmembrane transporter activity1
channel activity1
ligand-gated monoatomic ion channel activity1
binding1
membrane1
cell periphery1
plasma membrane bounded cell projection1
cell junction1
synaptic membrane1
postsynapse1
membrane protein complex1
transporter complex1
cation channel complex1
serotonin receptor complex1
neurotransmitter receptor complex1
cellular anatomical structure1

Protein interactions and networks

STRING

354 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HTR3EHTR3CQ8WXA8919
HTR3EHTR3DQ70Z44760
HTR3EHTR3AP46098714
HTR3EHTR3BO95264611
HTR3ESLC6A4P31645507
HTR3EHTR5AP47898500
HTR3EHTR2AP28223480
HTR3EHTR1FP30939478
HTR3EHTR1BP28222462
HTR3EHTR7P34969456
HTR3EHTR1EP28566450
HTR3EHTR1DP28221435
HTR3ETPH1P17752421
HTR3EHTR2BP41595410
HTR3ERIC3Q7Z5B4401

IntAct

4 interactions, top by confidence:

ABTypeScore
HTR3EARL6IP5psi-mi:“MI:0914”(association)0.530

BioGRID (12): ATP2A3 (Affinity Capture-MS), GET4 (Affinity Capture-MS), DHRS7 (Affinity Capture-MS), AMFR (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), AMFR (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), NPW (Affinity Capture-MS)

ESM2 similar proteins: A2A259, A5X5Y0, H2Q5A1, O46547, O70212, O95264, O97741, P01906, P01909, P02713, P02715, P02716, P04758, P04759, P04760, P07510, P09660, P09690, P11230, P13536, P18916, P20782, P23979, P25109, P25110, P35563, P37088, P37089, P46098, P55270, P78334, Q04844, Q07001, Q14246, Q5Y4N8, Q60HE8, Q61180, Q61549, Q70Z44, Q7Z418

Diamond homologs: A5X5Y0, O70212, O95264, P04757, P05376, P18845, P19370, P22770, P23979, P26153, P32297, P35563, P36544, P43143, P43679, P46098, P48182, P49581, P49582, P54131, Q05941, Q07263, Q15825, Q494W8, Q5IS76, Q68RJ7, Q70Z44, Q866A2, Q8R4G9, Q8WXA8, Q9I8C7, Q9JHJ5, Q9JJ16, A8WQK3, A8XNX8, O16926, O70174, O76554, P02716, P02717

SIGNOR signaling

2 interactions.

AEffectBMechanism
serotonin“up-regulates activity”HTR3E“chemical activation”
HTR3Eup-regulatesExcitatory_synaptic_transmission

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance64
Likely benign13
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

916 predictions. Top by Δscore:

VariantEffectΔscore
3:184104953:ACAGG:Adonor_loss1.0000
3:184104954:CAGG:Cdonor_loss1.0000
3:184104955:AGG:Adonor_loss1.0000
3:184104956:GGT:Gdonor_loss1.0000
3:184104957:G:GGdonor_gain1.0000
3:184104957:GT:Gdonor_loss1.0000
3:184104958:T:Adonor_loss1.0000
3:184105265:A:AGacceptor_gain1.0000
3:184105266:G:GAacceptor_gain1.0000
3:184105395:G:GTdonor_gain1.0000
3:184105395:G:Tdonor_gain1.0000
3:184105396:G:Tdonor_gain1.0000
3:184105428:G:GGdonor_gain1.0000
3:184105929:GA:Gdonor_gain1.0000
3:184105930:A:Gdonor_gain1.0000
3:184105968:CGGTA:Cdonor_loss1.0000
3:184105969:GGTA:Gdonor_loss1.0000
3:184105970:G:GGdonor_gain1.0000
3:184105971:T:Adonor_loss1.0000
3:184106125:CAGGT:Cacceptor_loss1.0000
3:184106126:A:AGacceptor_gain1.0000
3:184106127:G:GGacceptor_gain1.0000
3:184106127:GGT:Gacceptor_gain1.0000
3:184106304:G:GTdonor_gain1.0000
3:184106305:A:Tdonor_gain1.0000
3:184104785:A:AGacceptor_gain0.9900
3:184104785:AGCAT:Aacceptor_gain0.9900
3:184104786:G:GGacceptor_gain0.9900
3:184104786:GC:Gacceptor_gain0.9900
3:184104786:GCAT:Gacceptor_gain0.9900

AlphaMissense

3016 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
3:184105846:A:CS268R0.976
3:184105848:C:AS268R0.976
3:184105848:C:GS268R0.976
3:184104908:T:CF171L0.961
3:184104910:C:AF171L0.961
3:184104910:C:GF171L0.961
3:184104902:T:CF169L0.960
3:184104904:C:AF169L0.960
3:184104904:C:GF169L0.960
3:184106166:A:CS322R0.953
3:184106168:C:AS322R0.953
3:184106168:C:GS322R0.953
3:184105849:T:CF269L0.946
3:184105851:C:AF269L0.946
3:184105851:C:GF269L0.946
3:184105422:T:CF239L0.941
3:184105424:C:AF239L0.941
3:184105424:C:GF239L0.941
3:184104935:T:CF180L0.940
3:184104937:C:AF180L0.940
3:184104937:C:GF180L0.940
3:184105816:A:CS258R0.935
3:184105818:T:AS258R0.935
3:184105818:T:GS258R0.935
3:184105352:G:CW215C0.933
3:184105352:G:TW215C0.933
3:184105918:T:CF292L0.932
3:184105920:C:AF292L0.932
3:184105920:C:GF292L0.932
3:184105890:G:CK282N0.930

dbSNP variants (sampled 300 via entrez): RS1000141018 (3:184095203 C>T), RS1000190276 (3:184095553 G>A,T), RS1000294597 (3:184098053 A>C,G), RS1001142534 (3:184096535 A>G), RS1001144894 (3:184106584 T>A,C), RS1001194959 (3:184096883 C>A,T), RS1001710865 (3:184102302 A>G,T), RS1001729649 (3:184104713 T>A,C), RS1001747379 (3:184098591 T>G), RS1002096569 (3:184107455 G>A,C), RS1002169787 (3:184105542 T>C), RS1002441475 (3:184100924 G>A,C), RS1003079543 (3:184095579 C>T), RS1003424819 (3:184099667 T>C), RS1003532881 (3:184098351 A>C)

Disease associations

OMIM: gene MIM:610123 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST001469_1Major depressive disorder5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2094132 (PROTEIN COMPLEX GROUP), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL4296087 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 680,184 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1112ARIPIPRAZOLE424,205
CHEMBL1729CISAPRIDE414,365
CHEMBL289469GRANISETRON4431
CHEMBL3NICOTINE4184,969
CHEMBL42CLOZAPINE437,581
CHEMBL46ONDANSETRON441,386
CHEMBL56564TROPISETRON419,312
CHEMBL6437MIANSERIN414,778
CHEMBL708ZIPRASIDONE421,536
CHEMBL715OLANZAPINE440,057
CHEMBL86METOCLOPRAMIDE437,825
CHEMBL11IMIPRAMINE448,893
CHEMBL39SEROTONIN3186,160
CHEMBL18041ZACOPRIDE21,760
CHEMBL18772QUIPAZINE21,108
CHEMBL2107804BEMESETRON21,019
CHEMBL478CHLOROPHENYLPIPERAZINE23,138
CHEMBL7257MEBUFOTENIN21,595
CHEMBL214268PHA-543613166

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

PharmGKB variants

4 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs7432211HTR3E0.000
rs4912522HTR3E0.000
rs6443950HTR3E0.000
rs7627615HTR3E0.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — 5-HT3 receptors

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
5’-phenyl-(2’R)-spiro[4-azabicyclo[2.2.2]octane-2,2’-furo[2,3-b]pyridine]KI73 nM
[2,2’]Bithiophenyl-5-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amideKI1040 nM
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-phenylthiophene-2-carboxamideKI2020 nM
5-Phenyl-thiophene-2-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amideKI2020 nM

ChEMBL bioactivities

318 potent at pChembl≥5 of 324 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00Kd0.01nMCHEMBL143197
10.70Kd0.01995nMGRANISETRON
10.60Kd0.02512nMTROPISETRON
10.60Kd0.02512nMCHEMBL143197
10.20Kd0.0631nMTROPISETRON
10.15Ki0.071nMCHEMBL325422
10.10Kd0.07943nMONDANSETRON
10.10Kd0.07943nMGRANISETRON
10.10Kd0.07943nMZACOPRIDE
10.09IC500.08128nMCHEMBL416662
9.90Kd0.1259nMGRANISETRON
9.80Kd0.1585nMCHEMBL323208
9.80Kd0.1585nMCHEMBL40935
9.64Ki0.23nMCHEMBL43355
9.64Ki0.23nMCHEMBL327197
9.54IC500.2884nMCHEMBL299634
9.49Ki0.32nMCHEMBL111448
9.45IC500.3548nMCHEMBL53416
9.41Ki0.39nMCHEMBL111059
9.40Kd0.3981nMONDANSETRON
9.36Ki0.44nMCHEMBL113742
9.35IC500.4467nMQUIPAZINE
9.35Ki0.45nMCHEMBL325349
9.33Ki0.47nMCHEMBL113519
9.32Ki0.48nMCHEMBL320480
9.30Kd0.5012nMBEMESETRON
9.29Ki0.51nMCHEMBL315861
9.29Ki0.51nMCHEMBL333371
9.24Ki0.58nMCHEMBL112941
9.20Kd0.631nMCHEMBL40324
9.20Kd0.631nMONDANSETRON
9.17Ki0.68nMCHEMBL112237
9.16Ki0.69nMCHEMBL109322
9.15Ki0.7nMCHEMBL13535
9.10IC500.7943nMCHEMBL49932
9.10IC500.7943nMCHEMBL334923
9.08Ki0.83nMCHEMBL287987
9.07Ki0.86nMCHEMBL321477
9.06Ki0.88nMCHEMBL325235
9.04IC500.912nMCHEMBL51118
9.02Ki0.96nMCHEMBL113204
9.01IC500.9772nMCHEMBL54914
9.00Ki1nMCHEMBL54720
9.00EC501nMQUIPAZINE
9.00Kd1nMCHEMBL40883
9.00Kd1nMCHEMBL434999
8.96IC501.1nMIMIPRAMINE
8.96Ki1.1nMIMIPRAMINE
8.96Ki1.1nMCHEMBL108799
8.96Ki1.1nMCHEMBL112224

PubChem BioAssay actives

281 with measured affinity, of 612 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.

CompoundAssayTypeValueUnit
7-(4-prop-2-enylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic50<0.0001uM
1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd<0.0001uM
7-(4-benzylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic50<0.0001uM
4-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-7-chloropyrrolo[1,2-a]quinoxaline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0001uM
(1-methylindol-3-yl)-(4,5,6,7-tetrahydro-3H-benzimidazol-5-yl)methanone5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0001uM
Ondansetron6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd0.0001uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 1H-indole-3-carboxylate6026: Binding affinity to 5-hydroxytryptamine 3 receptor of neuronal in the afferent rabbit vaguskd0.0001uM
4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoxaline6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0002uM
6-(4-methylpiperazin-1-yl)-7,8,9,10-tetrahydrophenanthridine6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0002uM
(2-methyl-4-oxo-2-azabicyclo[3.3.1]nonan-8-yl) 1H-indole-3-carboxylate6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heartkd0.0002uM
(4-oxo-2-azatricyclo[3.3.1.02,7]nonan-8-yl) 1H-indole-3-carboxylate200911: Potency was evaluated on rabbit heart serotonergic receptorskd0.0002uM
4-(4-benzylpiperazin-1-yl)-7-chloropyrrolo[1,2-a]quinoxaline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0003uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-propan-2-ylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0003uM
4-(4-benzylpiperazin-1-yl)pyrrolo[1,2-a]quinoxaline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-butoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-(2-methylpropoxy)quinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-propylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0004uM
2-piperazin-1-ylquinoline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(2-methylpropyl)-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0005uM
7-fluoro-4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoline6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0005uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-phenylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0005uM
1-butyl-4-hydroxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoquinoline-3-carboxamide5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0005uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3,5-dichlorobenzoate6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd0.0005uM
(1,1-dimethylpiperidin-1-ium-4-yl)-(1H-indol-3-yl)methanone iodide6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heartkd0.0006uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-methoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0006uM
2-(3,4,5-trichlorophenyl)guanidine6339: Binding affinity to 5-HT3 serotonin receptor in NG 108-15 neuroblastoma glioma cells using [3H]GR-65630 radioligand.ki0.0007uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-butyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0007uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-(2-methylpropyl)quinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0007uM
10-(4-methylpiperazin-1-yl)-9-azatetracyclo[11.2.1.02,11.03,8]hexadeca-2(11),3,5,7,9-pentaene6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0008uM
7-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0008uM
N,N-dimethyl-2-[(Z)-(3-methylthieno[2,3-b]pyrrolizin-8-ylidene)amino]oxyethanamine6316: Compound was tested for binding affinity towards 5-hydroxytryptamine 3 receptoric500.0008uM
8-(4-prop-2-enylpiperazin-1-yl)-5-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0009uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-pentoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0009uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-ethoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0009uM
7-(4-methylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0010uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3,5-dimethylbenzoate6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd0.0010uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-pentylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0010uM
8-(4-benzylpiperazin-1-yl)-3-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaene1855131: Binding affinity to 5-HT3 receptor (unknown origin) assessed as inhibition constantki0.0010uM
1-azabicyclo[2.2.2]octan-3-yl 1H-indole-3-carboxylate6344: In vitro Binding affinity towards 5-hydroxytryptamine 3 receptor was determinedki0.0011uM
Imipramine2198785: Inhibition of 5HT receptor (unknown origin)ic500.0011uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-ethyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0011uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-hexyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0011uM
8-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]-5-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0012uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-benzyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0013uM
4-amino-N-[(4S,5R)-1-azabicyclo[3.3.1]nonan-4-yl]-5-chloro-2-methoxybenzamide6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heartkd0.0013uM
4-hydroxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2-oxo-1-phenylquinoline-3-carboxamide5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0014uM
7-piperazin-1-yl-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0015uM
N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-4-oxo-1H-quinoline-3-carboxamide5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0015uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(3-methylbutyl)-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0015uM
4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoxalin-7-ol143671: Effective concentration against 5-Hydroxytryptamine 3 receptor by measuring [14C]guanidinium uptake on NG108-15 cells.ec500.0016uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation, decreases methylation, increases mutagenesis2
aflatoxin B2increases methylation1
CGP 52608affects binding, increases reaction1
Resveratrolaffects cotreatment, decreases expression1
Estradioldecreases expression1
Phthalic Acidsincreases methylation1
Plant Extractsaffects cotreatment, decreases expression1
Rotenoneincreases expression1

ChEMBL screening assays

184 unique, capped per target: 119 binding, 64 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4368604BindingDisplacement of [3H]BRL 43694 from recombinant human 5-HT3 receptor at 10 uM after 120 mins by radiometric scintillation analysis relative to controlDesign, synthesis and evaluation of activity and pharmacokinetic profile of new derivatives of xanthone and piperazine in the central nervous system. — Bioorg Med Chem Lett
CHEMBL615717FunctionalCompound was tested for agonistic activity against 5-HT uptakeFirst tricyclic oximino derivatives as 5-HT3 ligands. — Bioorg Med Chem Lett
CHEMBL4413391ADMETAntagonist 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 methodIdentification of a novel DGKα inhibitor for XLP-1 therapy by virtual screening. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_YA56IDG-HEK293T-HTR3E-V5-OETransformed cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot