HTR4

Summary

HTR4 (5-hydroxytryptamine receptor 4, HGNC:5299) is a protein-coding gene on chromosome 5q32, encoding 5-hydroxytryptamine receptor 4 (Q13639). G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen.

This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described.

Source: NCBI Gene 3360 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 17 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000870

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5299
Approved symbol	HTR4
Name	5-hydroxytryptamine receptor 4
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	5-HT4
Ensembl gene	ENSG00000164270
Ensembl biotype	protein_coding
OMIM	602164
Entrez	3360

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000360693, ENST00000377888, ENST00000517929, ENST00000519495, ENST00000520086, ENST00000520514, ENST00000521124, ENST00000521530, ENST00000521735, ENST00000522588, ENST00000524063, ENST00000887163

RefSeq mRNA: 6 — MANE Select: NM_000870 NM_000870, NM_001040169, NM_001040172, NM_001040173, NM_001286410, NM_199453

CCDS: CCDS34270, CCDS34271, CCDS34272, CCDS34273, CCDS4291, CCDS75353

Canonical transcript exons

ENST00000377888 — 7 exons

Exon	Start	End
ENSE00001082935	148509456	148510024
ENSE00003494895	148523193	148523346
ENSE00003593351	148550137	148550262
ENSE00003593486	148548668	148548868
ENSE00003597593	148636989	148637061
ENSE00003900844	148481547	148483293
ENSE00003997493	148654062	148654527

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 91.41.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2601 / max 25.9807, expressed in 79 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64114	0.4339	199
64100	0.1596	53
64102	0.0494	25
64101	0.0402	19
64104	0.0069	2
64103	0.0040	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	91.41	silver quality
triceps brachii	UBERON:0001509	91.40	gold quality
olfactory bulb	UBERON:0002264	91.28	gold quality
diaphragm	UBERON:0001103	90.92	gold quality
gluteal muscle	UBERON:0002000	90.67	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.68	silver quality
tongue squamous epithelium	UBERON:0006919	89.68	gold quality
lateral globus pallidus	UBERON:0002476	88.95	gold quality
vena cava	UBERON:0004087	85.78	silver quality
vastus lateralis	UBERON:0001379	85.77	silver quality
quadriceps femoris	UBERON:0001377	85.29	silver quality
substantia nigra pars reticulata	UBERON:0001966	84.92	gold quality
substantia nigra pars compacta	UBERON:0001965	84.77	gold quality
epithelium of nasopharynx	UBERON:0001951	84.17	silver quality
gingival epithelium	UBERON:0001949	84.09	silver quality
body of tongue	UBERON:0011876	83.68	silver quality
lateral nuclear group of thalamus	UBERON:0002736	83.50	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.92	gold quality
biceps brachii	UBERON:0001507	82.68	gold quality
nasal cavity epithelium	UBERON:0005384	82.64	silver quality
hair follicle	UBERON:0002073	82.30	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.87	silver quality
upper arm skin	UBERON:0004263	81.50	silver quality
myocardium	UBERON:0002349	81.32	silver quality
subthalamic nucleus	UBERON:0001906	81.22	gold quality
cervix squamous epithelium	UBERON:0006922	80.88	silver quality
trabecular bone tissue	UBERON:0002483	80.54	gold quality
tongue	UBERON:0001723	80.44	gold quality
orbitofrontal cortex	UBERON:0004167	80.03	silver quality
gingiva	UBERON:0001828	79.95	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

138 targeting HTR4, 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-1193	100.00	65.93	529
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AB	99.95	71.31	3488

Literature-anchored findings (GeneRIF, showing 40)

• This paper presents an analysis of the SH3TC2 promoter after identifying a read-through transcript of the SH3TC2 and HTR4 loci. Available data suggests HTR4 is a separate locus with its own promoter, and not the product of a bi-cistronic transcript. (PMID:11716477)
• Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin. (PMID:11989623)
• The polymorphisms associated with mood disorder were located within the region that encodes the divergent C-terminal tails of the 5-HT(4) receptor. (PMID:12399948)
• report the activation of the extracellular signal-regulated kinases (ERKs) 1 and 2 (p44 and p42 MAP kinase) through the human serotonin receptors 5-HT(4(b)) and 5-HT(7(a)) (PMID:12446729)
• results show an overexpression of the 5-HT4 receptor in cisapride-responsive ACTH-independent bilateral macronodular adrenal hyperplasia (PMID:12519861)
• A highly significant association between schizophrenia and haplotype A-T (OR = 0.13 [0.03-0.58]) was detected. (PMID:12898568)
• Our results suggest a complex regulation of the h5-HT4 receptor gene expression involving distinct promoters and non-coding exons. (PMID:15575821)
• secretion of the non-amyloidogenic form of amyloid precursor protein, sAPPalpha induced by the 5-HT4(e) receptor isoform was not due to a general boost of the constitutive secretory pathway but rather to its specific effect on alpha-secretase activity (PMID:15710402)
• inhibition of Na+/H+ exchange activity by serotonin is mediated by 5-HT4 receptors in Caco-2 cells (PMID:15825078)
• coexpression of h5-HT4R and beta2-adrenergic receptor (beta2AR) led to their heterodimerization (PMID:15896782)
• the uncoupling and endocytosis of 5-HT4R require different GRK2 concentrations and involve distinct molecular events (PMID:15919661)
• development of an adenovirus expression system to examine the properties of two human 5-HT4 receptor splice variants, h5-HT4(b) and h5-HT4(d), expressed in adult cardiomyocytes devoid of native 5-HT4 receptors (PMID:15950987)
• These findings provide the first evidence of differential internalization between the two splice variants, 5-HT(4a) and 5-HT(4b) receptors. (PMID:16209130)
• We show overexpression & different splicing of 5-HT4 receptor in aldosterone-producing adenoma tissues in comparison with normal adrenocortical tissue.Isoforms (a) & (b) were not expressed in any APA but were present in majority of normal adrenal cortex. (PMID:16322401)
• These results suggest that the HTR4 gene may play a role in the genetic predisposition to ADHD. (PMID:16563621)
• Data show that 5-HT(4) receptor stimulation in primary neurons produced a potent but transient activation of the ERK pathway that is dependent on Src tyrosine kinase but totally independent of beta-arrestin. (PMID:17377064)
• We show that disulfide bridges between Cys112 and Cys145 located within transmembrane domain 3 and transmembrane domain 4, respectively, are of critical importance for 5-HT(4)R dimer formation. (PMID:17379184)
• Our results indicate that h5-HT(4(b)) is the dominant cardiac isoform of human 5-HT(4) receptors and its expression is increased in CAF. (PMID:17418812)
• Results describe regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors in the stomach and duodenum. (PMID:17509016)
• Functional activiy of 5-HT4 receptors was studied in children with congenital heart disease. (PMID:17603679)
• In this review, the pathways regulating either beta- or gamma-secretase may be differentially controlled by 5-HT4 receptor isoforms. (PMID:18322379)
• In failing human ventricle, 5-HT(4) receptor-mediated positive inotropic response was regulated by PDEs in a manner similar to that in postinfarction rat hearts;5-HT, PDE3 and PDE4 may have pathophysiological functions in heart failure. (PMID:18846035)
• 5-HT4 expression is lower in heart ventricle vs. atrium. Isoform expression in atrium and ventricle is similar. There is a parallel increase of cAMP and in the phosphorylation state of regulatory proteins following stimulation with 5-HT in the atrium. (PMID:19002436)
• The human 5HT4 receptor, when placed under the influence of the mouse opsin promoter and an opsin rod outer segment (ROS) targeting sequence, localized to ROS of transgenic mouse retina. (PMID:19053287)
• No association was found in the family sample betweewn HTR4 and schizophrenia. (PMID:19892407)
• Data show expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in lung tissue and indicate potential targets for interventions to alleviate respiratory disease. (PMID:20010834)
• This study demonistrated that 5-HT4 receptor is present in the human thalamus prenatally. (PMID:20538346)
• The relatively stable HT4 5- receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging. (PMID:21364600)
• SNP and haplotypes of the HTR4 gene were associated with the asthma phenotype and genetic variation of HTR4 may affect susceptibility to the development of asthma. (PMID:21382128)
• 5-HT4 receptor binding was a positively correlated to amyloid beta (A4) burden and negatively to MMSE score of the Alzheimer disease patients (PMID:21673407)
• HTR4 polymorphism associated with COPD risk and lung function decline (PMID:21965014)
• The occurrence of heterogeneous post-translational modifications (PTMs) on transgenic proteins, as well as the complications that non-native PTMs can cause, highlight the characterization of both endogenous and heterologous protein targets. (PMID:22145929)
• Mucosal 5-HT(4) receptor activation can mediate the prokinetic and antinociceptive actions of 5-HT(4)R agonists. (PMID:22226658)
• staining pattern of serotonin receptors in ovary indicates functional role in ovarian physiology. In ovarian tumours, expression is in harmony with a tumour suppressor role in ovarian carcinogenesis, which is supported by observations in the literature (PMID:22493371)
• Our findings are consistent with a model wherein the 5-HTTLPR S allele is associated with relatively increased serotonin levels. (PMID:22584237)
• These findings suggest that the 5-HT(4)R is critically involved in reward circuits that regulate people’s food intake (PMID:22709820)
• Results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction. (PMID:22837378)
• Our results suggest that HTR4 polymorphisms may not play a major role in the susceptibility for suicidal behavior in subjects with schizophrenia. (PMID:22842674)
• These results suggest a prominent role of 5-HT(4)R in promoting angiogenesis. (PMID:22903372)
• This is the first transgenic model to study human 5-HTreceptor in the atrium ex vivo or in vivo. (PMID:23307014)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr4	ENSDARG00000061940
mus_musculus	Htr4	ENSMUSG00000026322
rattus_norvegicus	Htr4	ENSRNOG00000019134

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), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

5-hydroxytryptamine receptor 4 — Q13639 (reviewed: Q13639)

Alternative names: Serotonin receptor 4

All UniProt accessions (4): A0A2D3FAF9, Q13639, E5RHV8, E5RK45

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. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. HTR4 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity.

Subunit / interactions. Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin). Interacts with MAGI2, MPP3, NHERF1 and SNX27 isoforms 1 and 2. Forms a complex including NHERF1 and EZR. Interacts with PATJ, NOS1 and SEC23A.

Subcellular location. Cell membrane. Endosome membrane.

Tissue specificity. Expressed in ileum, brain, and atrium, but not in the ventricle. Mainly expressed in atria and cardiac ventricle. Expressed in all cardiovascular tissues analyzed.

Domain organisation. Specificity for G(s) G alpha proteins is determined by the length of transmembrane regions 5 and 6 (TM5 and TM6).

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

Isoforms (9)

UniProt ID	Names	Canonical?
Q13639-1	5-HT4(B)	yes
Q13639-2	5-HT4(A), 5-HT4S
Q13639-3	5-HT4(C)
Q13639-4	5-HT4(D)
Q13639-5	5-HT4(E), H5-HT4(g)
Q13639-6	5-HT4(F)
Q13639-7	5-HT4(G)
Q13639-8	5-HT4(I)
Q13639-9	5-HT4c1

RefSeq proteins (6): NP_000861, NP_001035259, NP_001035262, NP_001035263, NP_001273339, NP_955525 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001520	5HT4_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (57 total): helix 14, mutagenesis site 10, topological domain 8, splice variant 8, transmembrane region 7, turn 3, binding site 2, sequence variant 2, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5EM9	X-RAY DIFFRACTION	1.6
7XT8	ELECTRON MICROSCOPY	3.1
7XT9	ELECTRON MICROSCOPY	3.2
7XTA	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13639-F1	81.60	0.58

Antibody-complex structures (SAbDab): 2 — 7XT8, 7XTA

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 (2): 100; 279

Disulfide bonds (1): 93–184

Glycosylation sites (1): 7

Mutagenesis-validated functional residues (10):

Position	Phenotype
100	abolished g-protein coupled receptor activity.
100	in d3.32n mutant; abolihed binding to serotonin.
104	decreased g-protein coupled receptor activity.
105	abolished g-protein coupled receptor activity.
186	decreased g-protein coupled receptor activity.
193	decreased g-protein coupled receptor activity.
197	in s5.43a mutant; abolihed binding to serotonin.
272	abolished g-protein coupled receptor activity.
275	abolished g-protein coupled receptor activity.
302	in y7.43a mutant; abolihed binding to serotonin. abolished g-protein coupled receptor activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-390666	Serotonin receptors
R-HSA-418555	G alpha (s) 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: 216 (showing top): MORF_RAGE, GOBP_DIGESTION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MORF_FLT1, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, MODULE_45, MODULE_64, MORF_ATRX, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, MORF_ESR1

GO Biological Process (14): 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-activating serotonin receptor signaling pathway (GO:0007192), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), chemical synaptic transmission (GO:0007268), maintenance of gastrointestinal epithelium (GO:0030277), regulation of appetite (GO:0032098), mucus secretion (GO:0070254), large intestinal transit (GO:0120056), regulation of postsynapse assembly (GO:0150052), system process (GO:0003008), signal transduction (GO:0007165), G protein-coupled serotonin receptor signaling pathway (GO:0098664)

GO Molecular Function (6): G protein-coupled serotonin receptor activity (GO:0004993), neurotransmitter receptor activity (GO:0030594), serotonin binding (GO:0051378), serotonin receptor activity (GO:0099589), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), dendrite (GO:0030425), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), endosome (GO:0005768), synapse (GO:0045202)

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
cellular anatomical structure	3
G protein-coupled serotonin receptor signaling pathway	2
transmembrane signaling receptor activity	2
synapse	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
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
serotonin receptor signaling pathway	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
epithelial structure maintenance	1
digestive system process	1
response to nutrient levels	1
regulation of biological quality	1
body fluid secretion	1
secretion by tissue	1
intestinal motility	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled serotonin receptor activity	1
G protein-coupled amine receptor activity	1
serotonin binding	1
signaling receptor activity	1
cation binding	1
amine binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
membrane	1

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR4	GIPR	P48546	639
HTR4	GIP	P09681	569
HTR4	KCNH2	Q12809	557
HTR4	OR52J3	Q8NH60	497
HTR4	LRRC10	Q5BKY1	462
HTR4	OR5B17	Q8NGF7	433
HTR4	OR5B3	Q8NH48	432
HTR4	NPR3	P17342	419
HTR4	MLN	P12872	395
HTR4	POMC	P01189	391
HTR4	REN	P00797	387
HTR4	ITGB3	P05106	372
HTR4	HTR3A	P46098	369
HTR4	AVPR1A	P37288	368
HTR4	CNGA4	Q8IV77	363

IntAct

40 interactions, top by confidence:

A	B	Type	Score
GPR37	HTR4	psi-mi:“MI:0915”(physical association)	0.580
GPR37	HTR4	psi-mi:“MI:2364”(proximity)	0.580
GPR37	HTR4	psi-mi:“MI:0403”(colocalization)	0.580
GPRIN2	HTR4	psi-mi:“MI:0915”(physical association)	0.510
HTR4	HTR4	psi-mi:“MI:2364”(proximity)	0.470
HTR4	HTR4	psi-mi:“MI:0915”(physical association)	0.470
	HTR4	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	HTR4	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR4	psi-mi:“MI:0915”(physical association)	0.400
HTR4	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
HTR4	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HTR4	psi-mi:“MI:0915”(physical association)	0.400
HTR4	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
TMEM230	HTR4	psi-mi:“MI:0915”(physical association)	0.370
CD81	HTR4	psi-mi:“MI:0915”(physical association)	0.370
CLTB	HTR4	psi-mi:“MI:0915”(physical association)	0.370
GDF1	HTR4	psi-mi:“MI:0915”(physical association)	0.370
GHITM	HTR4	psi-mi:“MI:0915”(physical association)	0.370
ANO10	HTR4	psi-mi:“MI:0915”(physical association)	0.370
CERS1	HTR4	psi-mi:“MI:0915”(physical association)	0.370
MGLL	HTR4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (22): GPRIN2 (Affinity Capture-Western), GPR37 (Affinity Capture-Western), GPRIN2 (Co-localization), GPR37 (Co-localization), GPRIN2 (Two-hybrid), GPR37 (Two-hybrid), TMEM230 (Two-hybrid), CD81 (Two-hybrid), CLTB (Two-hybrid), GDF1 (Two-hybrid), GHITM (Two-hybrid), ANO10 (Two-hybrid), CERS1 (Two-hybrid), MGLL (Two-hybrid), ELOVL5 (Two-hybrid)

ESM2 similar proteins: A0A678XMK4, A6QLE7, G3M4F8, O08890, O42384, O42574, O70528, P07550, P0C5J4, P10608, P17124, P18762, P25021, P25102, P28221, P28222, P28334, P28564, P28565, P28566, P30939, P30940, P35404, P35406, P46636, P47747, P56496, P60020, P60021, P61752, P79748, P97288, Q02284, Q0EAB5, Q13639, Q28044, Q28509, Q588Y6, Q61224, Q62758

Diamond homologs: A0A678XMK4, O02662, O02666, O14804, O19091, O42574, O70528, O77680, O77700, P07700, P11617, P17124, P18089, P21728, P23944, P25021, P25100, P25102, P25115, P28221, P28565, P35405, P35406, P42289, P42290, P42291, P43141, P46626, P47747, P47800, P49145, P50406, P53452, P53454, P60021, P61752, P79400, P97288, P97292, P97714

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
HTR4	“up-regulates activity”	GNAS	binding
HTR4	“up-regulates activity”	GNAL	binding
HTR4	“up-regulates activity”	GNAI1	binding
HTR4	“up-regulates activity”	GNAI3	binding
HTR4	“up-regulates activity”	GNAO1	binding
HTR4	“up-regulates activity”	GNAZ	binding
HTR4	“up-regulates activity”	GNAQ	binding
HTR4	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR4	“chemical activation”
serotonin	“up-regulates activity”	HTR4	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
calcium ion transport	5	45.3×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1965 predictions. Top by Δscore:

Variant	Effect	Δscore
5:148548826:C:CT	acceptor_gain	1.0000
5:148550131:GCTCA:G	donor_loss	1.0000
5:148550132:CTCA:C	donor_loss	1.0000
5:148550133:TCA:T	donor_loss	1.0000
5:148550134:CA:C	donor_loss	1.0000
5:148550136:C:CT	donor_loss	1.0000
5:148550258:CAGAA:C	acceptor_gain	1.0000
5:148550260:GAAC:G	acceptor_loss	1.0000
5:148550262:ACT:A	acceptor_loss	1.0000
5:148550263:C:CC	acceptor_gain	1.0000
5:148550263:C:CG	acceptor_loss	1.0000
5:148550264:T:C	acceptor_loss	1.0000
5:148654061:C:CT	donor_loss	1.0000
5:148654061:CCCG:C	donor_gain	1.0000
5:148509451:CTCA:C	donor_loss	0.9900
5:148509452:TCA:T	donor_loss	0.9900
5:148509453:CACC:C	donor_loss	0.9900
5:148509454:A:AC	donor_gain	0.9900
5:148509455:C:CA	donor_loss	0.9900
5:148509455:C:CC	donor_gain	0.9900
5:148509971:C:CT	acceptor_gain	0.9900
5:148510032:T:C	acceptor_gain	0.9900
5:148510032:T:TC	acceptor_gain	0.9900
5:148523184:GATAC:G	donor_loss	0.9900
5:148523185:ATACT:A	donor_loss	0.9900
5:148523186:TAC:T	donor_loss	0.9900
5:148523187:ACTC:A	donor_loss	0.9900
5:148523188:C:CG	donor_loss	0.9900
5:148523189:TCACC:T	donor_loss	0.9900
5:148523190:CACCA:C	donor_loss	0.9900

AlphaMissense

2552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:148509718:A:G	W272R	1.000
5:148509718:A:T	W272R	1.000
5:148509630:C:T	G301D	0.999
5:148509637:A:G	W299R	0.999
5:148509637:A:T	W299R	0.999
5:148509704:A:C	F276L	0.999
5:148509704:A:T	F276L	0.999
5:148509706:A:G	F276L	0.999
5:148509707:G:C	F275L	0.999
5:148509707:G:T	F275L	0.999
5:148509709:A:G	F275L	0.999
5:148509711:G:C	P274R	0.999
5:148509716:C:A	W272C	0.999
5:148509716:C:G	W272C	0.999
5:148509721:A:G	C271R	0.999
5:148509728:G:C	F268L	0.999
5:148509728:G:T	F268L	0.999
5:148509730:A:G	F268L	0.999
5:148509921:G:C	P204R	0.999
5:148509921:G:T	P204Q	0.999
5:148509929:G:C	F201L	0.999
5:148509929:G:T	F201L	0.999
5:148509931:A:G	F201L	0.999
5:148523264:A:G	W146R	0.999
5:148523264:A:T	W146R	0.999
5:148548668:C:A	R118M	0.999
5:148550178:G:C	N37K	0.999
5:148550178:G:T	N37K	0.999
5:148509575:A:C	F319L	0.998
5:148509575:A:T	F319L	0.998

dbSNP variants (sampled 300 via entrez): RS1000000263 (5:148481530 A>G), RS1000004399 (5:148452819 A>T), RS1000011599 (5:148492384 T>A), RS1000079867 (5:148622477 T>C), RS1000084690 (5:148483848 T>C), RS1000093875 (5:148499008 T>G), RS1000099746 (5:148567732 T>A,G), RS1000111497 (5:148544890 A>C), RS1000112089 (5:148535715 C>G,T), RS1000124042 (5:148561643 C>G), RS1000131562 (5:148488071 G>A), RS1000138970 (5:148536052 C>T), RS1000139377 (5:148640564 G>A), RS1000183328 (5:148631096 T>C), RS1000185381 (5:148545207 A>G)

Disease associations

OMIM: gene MIM:602164 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096)

Orphanet (1): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000542_7	Pulmonary function	1.000000e-11
GCST000544_5	Pulmonary function	4.000000e-09
GCST001588_14	Periodontal microbiota	2.000000e-06
GCST001621_2	Airflow obstruction	4.000000e-09
GCST001784_1	Pulmonary function (smoking interaction)	5.000000e-17
GCST004147_10	Chronic obstructive pulmonary disease	5.000000e-26
GCST004183_5	Lung function (FEV1)	2.000000e-11
GCST004185_39	Lung function (FEV1/FVC)	8.000000e-23
GCST007267_48	Systolic blood pressure	6.000000e-14
GCST007268_72	Diastolic blood pressure	2.000000e-10
GCST007429_11	Lung function (FVC)	6.000000e-06
GCST007430_106	Peak expiratory flow	6.000000e-33
GCST007431_100	Lung function (FEV1/FVC)	2.000000e-96
GCST007432_165	FEV1	7.000000e-47
GCST007611_18	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	1.000000e-13
GCST007692_54	Chronic obstructive pulmonary disease	3.000000e-33
GCST007941_26	Medication use (adrenergics, inhalants)	7.000000e-09
GCST008357_10	Mood instability	1.000000e-08
GCST008647_9	Urinary sodium excretion	9.000000e-12
GCST008659_4	Lung function in heavy smokers (low FEV1 vs high FEV1)	5.000000e-09
GCST008664_6	Lung function (low FEV1 vs high FEV1)	9.000000e-11
GCST90002383_217	Hematocrit	1.000000e-09
GCST90002384_116	Hemoglobin	3.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0009941	Inhalant adrenergic use measurement
EFO:0008475	mood instability measurement
EFO:0009282	sodium measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1875 (SINGLE PROTEIN), CHEMBL2096904 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

17 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 318,182 (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
CHEMBL117287	PRUCALOPRIDE	4	2,516
CHEMBL1729	CISAPRIDE	4	14,365
CHEMBL56564	TROPISETRON	4	19,312
CHEMBL76370	TEGASEROD	4	4,580
CHEMBL86	METOCLOPRAMIDE	4	37,825
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL39	SEROTONIN	3	186,160
CHEMBL2087337	VELUSETRAG	2	107
CHEMBL2402904	FELCISETRAG	2	158
CHEMBL3306918	PRX-03140	2	147
CHEMBL356359	PIBOSEROD	2	316
CHEMBL471036	LITOXETINE	2	2,122
CHEMBL7257	MEBUFOTENIN	2	1,595
CHEMBL2152922	PF-04995274	1	23
CHEMBL2179582	PF-03382792	1
CHEMBL3950712	DA-6886	1	11
CHEMBL4297327	SUVN-D4010	1	52

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1971431	HTR4		0.00	0
rs4264931	HTR4		0.00	0
rs2068190	HTR4		0.00	0
rs1862342	HTR4		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 (42 total), top 25:

Ligand	Action	Affinity	Parameter
RS 100235	Antagonist	12.2	pKi
GR 125487	Antagonist	10.7	pKi
SB 204070	Antagonist	10.41	pKi
piboserod	Antagonist	10.4	pKi
GR 113808	Antagonist	10.3	pKi
SB 207710	Antagonist	10.3	pKi
[3H]GR 113808	Antagonist	10.3	pKd
[123I]SB 207710	Antagonist	10.07	pKd
ML 10375	Antagonist	10.0	pKi
PF-04995274	Partial agonist	9.82	pKi
[3H]RS 57639	Antagonist	9.7	pKd
RS 116 0086	Inverse agonist	9.5	pKi
TD-8954	Agonist	9.4	pKi
RO 116 1148	Inverse agonist	9.3	pKi
capeserod	Partial agonist	9.2	pKi
ML 10302	Partial agonist	9.0	pKi
RS 57639	Partial agonist	8.9	pKi
SB 203186	Antagonist	8.9	pKi
RS67506	Agonist	8.8	pEC50
RS 67333	Partial agonist	8.7	pKi
RS 39604	Antagonist	8.7	pKi
[11C]SB207145	Antagonist	8.6	pKd
prucalopride	Partial agonist	8.6	pKi
tegaserod	Partial agonist	8.4	pKi
BIMU 1	Full agonist	8.4	pKi

Binding affinities (BindingDB)

137 measured of 143 human assays (154 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-amino-5-chloro-N-[[2-(1H-indol-3-ylmethyl)piperidin-4-yl]methyl]-2-methoxybenzamide	IC50	0.002 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-N-[[1-(5-indol-1-ylpentyl)piperidin-4-yl]methyl]-2-methoxybenzamide	IC50	0.005 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-N-[[1-(3-indol-1-ylpropyl)piperidin-4-yl]methyl]-2-methoxybenzamide	IC50	0.039 nM	US-9221790: Benzamide derivatives
SB207710	KI	0.05 nM
4-amino-5-chloro-2-methoxy-N-[[1-[3-(triazol-1-yl)propyl]piperidin-4-yl]methyl]benzamide	IC50	0.067 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-[(1-methylindol-3-yl)methyl]piperidin-4-yl]methyl]benzamide	IC50	0.076 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-[5-(triazol-1-yl)pentyl]piperidin-4-yl]methyl]benzamide	IC50	0.103 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-N-[[1-[(4-fluorophenyl)methyl]piperidin-4-yl]methyl]-2-methoxybenzamide	IC50	0.134 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-[3-(tetrazol-1-yl)propyl]piperidin-4-yl]methyl]benzamide	IC50	0.164 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-[3-(triazol-2-yl)propyl]piperidin-4-yl]methyl]benzamide	IC50	0.182 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-[3-(1,2,4-triazol-1-yl)propyl]piperidin-4-yl]methyl]benzamide	IC50	0.226 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-[3-(2-methylimidazol-1-yl)propyl]piperidin-4-yl]methyl]benzamide	IC50	0.229 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-2-methoxy-N-[[1-(pyridin-3-ylmethyl)piperidin-4-yl]methyl]benzamide	IC50	0.267 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-N-[[1-[(4-hydroxyphenyl)methyl]piperidin-4-yl]methyl]-2-methoxybenzamide	IC50	0.375 nM	US-9221790: Benzamide derivatives
ML10375	KI	0.41 nM
4-amino-5-chloro-2-methoxy-N-[[1-[(1-methylpyrrol-2-yl)methyl]piperidin-4-yl]methyl]benzamide	IC50	0.421 nM	US-9221790: Benzamide derivatives
4-amino-5-chloro-N-[[1-(1H-imidazol-2-ylmethyl)piperidin-4-yl]methyl]-2-methoxybenzamide	IC50	0.454 nM	US-9221790: Benzamide derivatives
CHEMBL2059582	KI	0.794 nM
[1-(cyclohexylmethyl)piperidin-4-yl]methyl 4-amino-5-chloro-2-methoxybenzoate	KI	0.9 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
CHEMBL2059578	KI	1 nM
CHEMBL2059580	KI	1 nM
14C-5-hydroxy tryptamine creatinine disulfate	KI	1.2 nM
6-Chloro-8-[5-(1-cyclobutyl-piperidin-4-yl)-[1,3,4]oxadiazol-2-yl]-chroman-5-ylamine	EC50	1.3 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
CAS_135938-17-9	KI	1.3 nM
CHEMBL2059584	KI	1.58 nM
CHEMBL3329226	KI	1.6 nM
ML10302 scaffold, 9{b;w}	KI	2 nM
CHEMBL2059577	KI	2 nM
6-Chloro-8-[5-(1-cyclopentyl-piperidin-4-yl)-[1,3,4]oxadiazol-2-yl]-chroman-5-ylamine	EC50	2.3 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
4-amino-5-chloro-[[1-(cyclohexylmethyl)-4-piperidyl]methyl]-2-methoxybenzamide	KI	2.3 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
6-Chloro-8-{5-[1-(3-methyl-butyl)-piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-chroman-5-ylamine	EC50	2.4 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-[(piperidin-4-yl)methyl]-4-piperidyl] propan-1-one	KI	2.5 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
1-[4-amino-5-chloro-2-(2-fluoroéthoxy)phenyl]-3-[1-(cyclohexylmethyl)-4-piperidyl]propan-1-one	KI	2.5 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
CHEMBL2059583	KI	2.51 nM
CHEMBL2059586	KI	2.51 nM
CHEMBL2059588	KI	2.51 nM
1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(cyclopentylmethyl)piperidin-4-yl]propan-1-one	KI	3 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
1-(4-amino-5-fluoro-2-methoxyphenyl)-3-[1-(cyclohexylmethyl)-4-piperidyl]propan-1-one	KI	3.8 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(cycloheptylmethyl)piperidin-4-yl]propan-1-one	KI	3.9 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
CHEMBL2059579	KI	3.98 nM
CHEMBL2059585	KI	3.98 nM
CHEMBL2059581	KI	3.98 nM
ML10302 scaffold, 9{a;y}	EC50	4 nM
6-Chloro-8-[5-(3-cyclobutyl-3-aza bicyclo[3.1.0]hex-6-yl)-[1,3,4]oxadiazol-2-yl]chroman-5-ylamine	EC50	4.2 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
ML10302 scaffold, 9{a;q}	KI	5 nM
4-[5-(4-Amino-5-chloro-2,3-dihydro-benzofuran-7-yl)-[1,3,4]oxadiazol-2-yl]-[1,4′]bipiperidinyl-1′-carboxylicacid ethyl ester	EC50	5 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
4-amino-5-bromo-N-[[1-(cyclohexylmethyl)-4-piperidyl]methyl]-2-methoxybenzamide	KI	5.4 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
6-Chloro-8-[5-(1-cyclobutylmethyl-piperidin-4-yl)-[1,3,4]oxadiazol-2-yl]-chroman-5-ylamine	EC50	5.7 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
6-Chloro-8-{5-[1-(tetrahydro-pyran-4-yl)-piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-chroman-5-ylamine	EC50	5.7 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands
6-Chloro-8-[5-(1-cyclobutylmethyl-piperidin-4-yl)-[1,3,4]oxadiazol-2-yl]-2,3-dihydro-benzo[1,4]dioxin-5-ylamine	EC50	6.2 nM	US-9636335: Heteroaryl compounds as 5-HT4 receptor ligands

ChEMBL bioactivities

1094 potent at pChembl≥5 of 1099 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	Ki	0.01585	nM	CHEMBL180835
10.80	Ki	0.01585	nM	CHEMBL68131
10.60	Ki	0.02512	nM	CHEMBL361118
10.60	Ki	0.02512	nM	CHEMBL181202
10.50	Ki	0.03162	nM	CHEMBL367354
10.50	Ki	0.03162	nM	CHEMBL181126
10.50	Ki	0.03162	nM	CHEMBL182999
10.41	IC50	0.039	nM	CHEMBL3967117
10.40	Ki	0.03981	nM	CHEMBL2181170
10.40	Ki	0.04	nM	CHEMBL2181170
10.40	Ki	0.03981	nM	CHEMBL33884
10.37	Ki	0.04266	nM	CHEMBL1632165
10.30	Ki	0.05012	nM	CHEMBL2440460
10.30	Ki	0.05012	nM	CHEMBL424790
10.30	Ki	0.05012	nM	CHEMBL180680
10.30	Ki	0.05012	nM	CHEMBL3329805
10.28	Ki	0.05248	nM	PIBOSEROD
10.27	Ki	0.0537	nM	CHEMBL1632163
10.20	Ki	0.0631	nM	CHEMBL2440457
10.20	Ki	0.0631	nM	CHEMBL180201
10.19	Ki	0.06457	nM	CHEMBL1632169
10.17	IC50	0.067	nM	DA-6886
10.15	EC50	0.07	nM	CHEMBL6171570
10.13	Ki	0.07413	nM	CHEMBL33884
10.12	IC50	0.076	nM	CHEMBL3934371
10.11	Ki	0.078	nM	CHEMBL33884
10.10	Ki	0.07943	nM	CHEMBL2177130
10.10	Ki	0.07943	nM	CHEMBL360449
10.10	Ki	0.07943	nM	CHEMBL3329814
10.00	Ki	0.1	nM	CHEMBL2179697
10.00	Ki	0.1	nM	PIBOSEROD
10.00	Ki	0.1	nM	CHEMBL180830
10.00	Ki	0.1	nM	CHEMBL360245
10.00	EC50	0.1	nM	CHEMBL4215329
10.00	Ki	0.1	nM	CHEMBL33884
9.99	IC50	0.103	nM	CHEMBL3926377
9.99	Ki	0.1023	nM	CHEMBL1632157
9.97	Ki	0.1072	nM	CHEMBL1632158
9.96	Ki	0.11	nM	CHEMBL3093186
9.90	Ki	0.1259	nM	CHEMBL2391994
9.90	Ki	0.1259	nM	CHEMBL179833
9.90	Ki	0.1259	nM	CHEMBL178285
9.90	Ki	0.1259	nM	CHEMBL178669
9.87	IC50	0.134	nM	CHEMBL3890747
9.85	Ki	0.1413	nM	CHEMBL1632167
9.82	Ki	0.15	nM	PF-04995274
9.80	Ki	0.1585	nM	CHEMBL2179699
9.80	Ki	0.1585	nM	PIBOSEROD
9.80	Ki	0.1585	nM	CHEMBL181415
9.80	Ki	0.1585	nM	CHEMBL180697

PubChem BioAssay actives

941 with measured affinity, of 2064 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-[2-(methanesulfonamido)ethyl]piperidin-4-yl]methyl 1-methylindole-3-carboxylate	754104: Displacement of [3H]GR113808 from human 5-HT4B receptor expressed in HEK293 cells after 1 hr by liquid scintillation counting analysis	ki	<0.0001	uM
(1-butylpiperidin-4-yl)methyl 5-amino-6-chloro-2,3-dihydro-1,4-benzodioxine-8-carboxylate	416400: Binding affinity at 5HT4 receptor	ki	<0.0001	uM
N-[[1-[3-(4-butan-2-ylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	<0.0001	uM
benzyl 5-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]pentanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	<0.0001	uM
benzyl 4-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]butanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	<0.0001	uM
7-fluoro-5-[(1-propylpiperidin-4-yl)methoxy]benzo[h][1,6]naphthyridine	1057029: Binding affinity to human 5HT4R	ki	<0.0001	uM
methanesulfonic acid;[1-[[4-(2-methoxycarbonylphenyl)phenyl]methyl]piperidin-4-yl]methyl 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxylate	781013: Displacement of [3H]GR113808 from human 5HT4B receptor expressed in HEK293 cells	ki	<0.0001	uM
N-[[1-[3-(4-propylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	<0.0001	uM
N-[[1-[3-[4-(4-fluorophenyl)sulfonylpiperazin-1-yl]sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	<0.0001	uM
N-[[1-[3-(4-propan-2-ylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	<0.0001	uM
N-[[1-[3-(8-azaspiro[4.5]decan-8-ylsulfonyl)propyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	<0.0001	uM
N-[[1-[3-(4-cyclopentylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	<0.0001	uM
N-[[1-[[4-(2-methylpropylsulfonylamino)phenyl]methyl]piperidin-4-yl]methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide	1160988: Displacement of [3H]GR113808 from human 5HT4b receptor expressed in HEK293 cell membranes	ki	0.0001	uM
N-[[1-(oxan-4-ylmethyl)piperidin-4-yl]methyl]-2-propan-2-ylpyrazolo[1,5-a]pyridine-7-carboxamide	1375752: Agonist activity at recombinant human 5-HT4E receptor expressed in CHO cells assessed as induction of c-AMP accumulation after 4 hrs by luciferase reporter assay	ec50	0.0001	uM
N-[[1-[3-(4-propylsulfonylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[(1-butylpiperidin-4-yl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0001	uM
1-propan-2-yl-N-[[1-(2-pyridin-2-ylethyl)piperidin-4-yl]methyl]indazole-3-carboxamide;hydrochloride	707296: Displacement of 3Hmethyl 1-methyl-1H-indole-3-carboxylate from human 5HT4R expressed in HEK293 cells	ki	0.0001	uM
N-[[1-[3-(4-acetylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-[3-[4-(furan-2-carbonyl)piperazin-1-yl]sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-[3-(4-pyrrolidin-1-ylsulfonylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-[3-(4,4-dimethylpiperidin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-[3-(4-propan-2-ylsulfonylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
methyl 2-[4-[[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]methyl]phenyl]benzoate	781013: Displacement of [3H]GR113808 from human 5HT4B receptor expressed in HEK293 cells	ki	0.0001	uM
2-[4-[[4-(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonyloxymethyl)piperidin-1-yl]methyl]phenyl]-2-methylpropanoic acid	754104: Displacement of [3H]GR113808 from human 5-HT4B receptor expressed in HEK293 cells after 1 hr by liquid scintillation counting analysis	ki	0.0001	uM
2,2-dimethylpropanoyloxymethyl 6-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]hexanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0001	uM
benzyl 6-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]hexanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0001	uM
tert-butyl 6-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]hexanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0001	uM
methyl 6-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]hexanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0001	uM
ethyl 4-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]butanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0001	uM
4-[[4-[[4-[(3R)-oxolan-3-yl]oxy-1,2-benzoxazol-3-yl]oxymethyl]piperidin-1-yl]methyl]oxan-4-ol	706253: Displacement of [3H]GR113808 from human 5HT4D receptor expressed in HEK293 cells after 30 mins by liquid scintillation counting	ki	0.0001	uM
2-[4-[[4-(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonyloxymethyl)piperidin-1-yl]methyl]phenyl]benzoic acid;methanesulfonic acid	781013: Displacement of [3H]GR113808 from human 5HT4B receptor expressed in HEK293 cells	ki	0.0001	uM
7-fluoro-5-[[1-(3,3,3-trifluoropropyl)piperidin-4-yl]methoxy]benzo[h][1,6]naphthyridine	1057029: Binding affinity to human 5HT4R	ki	0.0001	uM
[1-(2,3-dihydroxypropyl)piperidin-4-yl]methyl 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxylate	1160988: Displacement of [3H]GR113808 from human 5HT4b receptor expressed in HEK293 cell membranes	ki	0.0001	uM
N-[[1-[3-[4-(4-fluorophenyl)piperazin-1-yl]sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-[3-(4-ethylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-[3-(4-propylpiperidin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0001	uM
N-[[1-(2-phenylethyl)piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide;hydrochloride	707296: Displacement of 3Hmethyl 1-methyl-1H-indole-3-carboxylate from human 5HT4R expressed in HEK293 cells	ki	0.0001	uM
N-[[1-(3-piperazin-1-ylsulfonylpropyl)piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0002	uM
N-[[1-[2-(4-aminophenyl)ethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide;dihydrochloride	707296: Displacement of 3Hmethyl 1-methyl-1H-indole-3-carboxylate from human 5HT4R expressed in HEK293 cells	ki	0.0002	uM
N-[[1-[[4-(methanesulfonamido)phenyl]methyl]piperidin-4-yl]methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide	1160988: Displacement of [3H]GR113808 from human 5HT4b receptor expressed in HEK293 cell membranes	ki	0.0002	uM
N-[[1-[[4-(cyclohexylsulfonylamino)phenyl]methyl]piperidin-4-yl]methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide	1160988: Displacement of [3H]GR113808 from human 5HT4b receptor expressed in HEK293 cell membranes	ki	0.0002	uM
N-[[1-[[4-(methanesulfonamido)phenyl]methyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	1160988: Displacement of [3H]GR113808 from human 5HT4b receptor expressed in HEK293 cell membranes	ki	0.0002	uM
N-[[1-[[4-(2-methylpropylsulfonylamino)phenyl]methyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	1160988: Displacement of [3H]GR113808 from human 5HT4b receptor expressed in HEK293 cell membranes	ki	0.0002	uM
N-[[1-(2-cyclohexylethyl)piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide;hydrochloride	707296: Displacement of 3Hmethyl 1-methyl-1H-indole-3-carboxylate from human 5HT4R expressed in HEK293 cells	ki	0.0002	uM
(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
N-[[1-(3-piperidin-1-ylsulfonylpropyl)piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0002	uM
N-[[1-[3-[4-(pyridin-3-ylmethyl)piperazin-1-yl]sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide	239909: Inhibitory constant for human cloned 5-HT4 receptor	ki	0.0002	uM
(1-butylpiperidin-4-yl)methyl 4-amino-2-methoxybenzoate	517043: Agonist activity at 5HT4 receptor expressed in HEK293/L9 cells by cAMP assay	ec50	0.0002	uM
methyl 10-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]decanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0002	uM
tert-butyl 4-[4-[(3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carbonylamino)methyl]piperidin-1-yl]butanoate	548651: Displacement of [3H]GR113808 from human 5HT4 receptor expressed in HEK293 cells by liquid scintillation counting	ki	0.0002	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tegaserod	affects binding, increases activity	2
Valproic Acid	decreases methylation, increases expression	2
psilocin	increases response to substance, increases phosphorylation, increases activity	1
sodium arsenite	affects methylation	1
GR 113808	affects binding	1
CGP 52608	affects binding, increases reaction	1
2-piperidinoethyl 4-amino-5-chloro-2-methoxybenzoate	affects binding, increases activity	1
bazedoxifene	increases expression	1
Zoledronic Acid	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation, affects methylation	1
Etoposide	affects response to substance	1
Lipopolysaccharides	increases secretion, increases reaction, decreases reaction	1
Piperazines	affects binding, decreases activity	1
Psilocybin	increases phosphorylation, increases activity, increases response to substance	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

349 unique, capped per target: 233 binding, 113 functional, 2 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000204	Binding	Binding affinity to 5HT4e receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1048160	Functional	Agonist activity at human recombinant 5-HT4 receptor	mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). — Bioorg Med Chem Lett
CHEMBL1738126	Unclassified	PUBCHEM_BIOASSAY: Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki. (Class of assay: screening) [Related pubchem assays (depositor defined):AID1792, AID1796, AID1823, AID253	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 1 transformed cell line, 1 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0SZ	ACTOne HTR4	Transformed cell line	Female
CVCL_D7RL	Ubigene A-549 HTR4 KO	Cancer cell line	Male
CVCL_H382	CHO-K1/5-HT4/Galpha15	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00126581	PHASE2	COMPLETED	Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00511485	PHASE2	COMPLETED	Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03)
NCT00950365	PHASE2	COMPLETED	Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
NCT00955305	PHASE2	TERMINATED	Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT01218516	PHASE2	COMPLETED	A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung
NCT01294306	PHASE2	COMPLETED	MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy
NCT01557959	PHASE2	COMPLETED	Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
NCT01561456	PHASE2	COMPLETED	Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung
NCT01578551	PHASE2	TERMINATED	Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.
NCT01578668	PHASE2	COMPLETED	Erlotinib Plus Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases
NCT01819428	PHASE2	TERMINATED	NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma
NCT01935336	PHASE2	COMPLETED	Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
NCT02134912	PHASE2	TERMINATED	S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib
NCT02186847	PHASE2	COMPLETED	Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer