HRH2

Summary

HRH2 (histamine receptor H2, HGNC:5183) is a protein-coding gene on chromosome 5q35.2, encoding Histamine H2 receptor (P25021). G-protein coupled receptor for histamine, primarily mediating gastric acid secretion.

Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. Histamine receptor H2 belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and stimulates gastric acid secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3274 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 28 total
• Druggable target: yes — 115 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001367711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5183
Approved symbol	HRH2
Name	histamine receptor H2
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113749
Ensembl biotype	protein_coding
OMIM	142703
Entrez	3274

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000377291, ENST00000624694, ENST00000636584, ENST00000932189, ENST00000932190, ENST00000955811

RefSeq mRNA: 4 — MANE Select: NM_001367711 NM_001131055, NM_001367711, NM_001393460, NM_001393461

CCDS: CCDS47344, CCDS93828

Canonical transcript exons

ENST00000636584 — 3 exons

Exon	Start	End
ENSE00001473444	175682709	175684309
ENSE00003800377	175707779	175710756
ENSE00003928235	175658071	175658155

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 94.17.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2880 / max 234.5635, expressed in 627 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60363	3.5695	580
60362	0.5681	270
60361	0.1255	62
60360	0.0249	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.17	gold quality
leukocyte	CL:0000738	94.01	gold quality
blood	UBERON:0000178	92.82	gold quality
granulocyte	CL:0000094	91.06	gold quality
heart left ventricle	UBERON:0002084	88.58	gold quality
cardiac ventricle	UBERON:0002082	88.17	gold quality
apex of heart	UBERON:0002098	87.44	gold quality
body of stomach	UBERON:0001161	84.82	gold quality
heart	UBERON:0000948	84.03	gold quality
putamen	UBERON:0001874	83.75	gold quality
caudate nucleus	UBERON:0001873	83.70	gold quality
left ventricle myocardium	UBERON:0006566	82.36	gold quality
prefrontal cortex	UBERON:0000451	82.18	gold quality
bone marrow cell	CL:0002092	82.08	gold quality
nucleus accumbens	UBERON:0001882	81.93	gold quality
spleen	UBERON:0002106	81.85	gold quality
right frontal lobe	UBERON:0002810	81.73	gold quality
stomach	UBERON:0000945	81.66	gold quality
right atrium auricular region	UBERON:0006631	81.24	gold quality
primary visual cortex	UBERON:0002436	81.06	gold quality
cardiac atrium	UBERON:0002081	80.72	gold quality
bone marrow	UBERON:0002371	80.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.52	gold quality
heart right ventricle	UBERON:0002080	80.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.05	gold quality
frontal cortex	UBERON:0001870	79.77	gold quality
neocortex	UBERON:0001950	79.25	gold quality
right coronary artery	UBERON:0001625	79.12	gold quality
cortical plate	UBERON:0005343	78.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting HRH2, 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-6825-5P	99.96	69.81	3431
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-5591-3P	96.23	67.03	489
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-6734-5P	95.70	65.56	950
HSA-LET-7I-3P	88.33	62.89	81

Literature-anchored findings (GeneRIF, showing 40)

• Histamine H2 receptors regulate intracellular Ca2+ levels exclusively by activation of nonselective cation channels, an effect which is inhibited via specific activation of protein kinase C isoform. (PMID:11466390)
• could be detected at the feto-maternal interface of human (PMID:11603849)
• H2r exposure to an agonist caused desensitization controlled by H2r phosphorylation via GRK2 and GRK3. (PMID:11641433)
• histamine up-regulates LOX-1 expression via the H2 receptor in THP-1 monocytes (PMID:11728449)
• expressed on monocyte-derived dendritic cells (PMID:11898002)
• markedly different potency for activation of multiple signaling pathways by H1- and H2-HRs (PMID:12680587)
• No significant differences in H1R or H2R mRNA levels between seasonal allergic rhinitic and nonrhinitic subjects in-season, despite observed differences in H reactivity. (PMID:12757445)
• Stimulation of phosphodiesterase IV is mediated by the H2 receptor and related to intracellular levels of cAMP. (PMID:12824943)
• Data show that the rapid and prolonged modulation of cell surface histamine H2 receptor levels by histamine was regulated solely via internalization. (PMID:14523557)
• significant differences in H2 receptor expression in different vascular cell types might play a critical role in histamine induced cellular responses (PMID:15167968)
• human mast cells constitutively express primarily H2 and H4 receptors and that H2 receptors are functionally linked to cellular processes. (PMID:15191551)
• expression of the histamine (H) receptors 1 (H1) and 2 (H2) by germinal, interstitial, and peritubular cells in the testes of fertile and infertile patients (PMID:15820830)
• Involvement of histamine H2 receptors in the histamine induced ets-1 expression in melanoma cells (PMID:15848191)
• expression in chondrocytes of osteoarthritic cartilage (PMID:15928843)
• The equilibrium between receptor endocytosis and recycling is altered before H2R upregulation, probably via suppressing H2R degradation. (PMID:15961859)
• histamine exerts both a proproliferative and a proangiogenic effect via H2/H4 receptor activation, mediated by increasing COX-2-related PGE2 production in COX-2-expressing colon cancer cells (PMID:16203768)
• These data suggest postexercise skeletal muscle hyperemia exists in endurance trained men and women. (PMID:16888049)
• The point mutation Cys-17 to Tyr-17 in the human histamine H2 receptor results in the formation of an H-bond between Tyr-17 and Asp-271 , favoring the stabilization of an active receptor conformation. (PMID:17347323)
• Histamine excites human enteric neurones and this effect involves histamine H1-4 receptors. (PMID:17627982)
• a dramatic alteration in the distribution of histamine receptors in colon cancer (PMID:18258331)
• HRH2 trafficking was analyzed by examination of the roles of arrestin, dynamin, and clathrin on HRH2 internalization. (PMID:18617631)
• These results suggest that the agonist-induced H2R internalization and ERK1/2 activation are partially dynamin-dependent. Furthermore, ERK1/2 activation via H2R is likely dependent of the endocytotic process rather than dynamin itself. (PMID:18691388)
• role in allergy, autoimmunity, graft rejection, malignancy (PMID:18802338)
• expression of H(2) during nicotinamide-induced differentiation of human amniotic epithelial cells into pancreatic beta-like cells may define a time-point, indicating involvement of histamine at the earlier stages (PMID:20012462)
• Results describe the interactions between human H2 receptor and its agonists. (PMID:21212009)
• Excitation of dentate nucleus neurons by histamine suggests that initiation and planning of movement is modulated by histaminergic projections. (PMID:21683759)
• GRK2 induces desensitization of H2R through a phosphorylation-independent and RGS-dependent mechanism (PMID:21705320)
• evidence supports the involvement of histaminergic and gamma-aminobutyric acidergic mechanisms in the etiology of TS and show an overlap of rare CNVs in TS and autism spectrum disorder. (PMID:22169095)
• 1018 GG homozygosity of HRH2 may be associated with the severity of gastric mucosal atrophy (PMID:22615049)
• The results suggest that HRH2 -1018 GG homozygote is a risk factor for the severity of gastric mucosal atrophy under the influence of H. pylori infection, especially in older subjects. (PMID:22720301)
• [review] The H1, H2, and H3 receptors are all involved in recovery of neurological function when extracellular histamine is gradually increasing, after cerebral ischemia. (PMID:22860191)
• HR2 receptor is involved in histamine-induced GDF-15 expression. (PMID:22975449)
• rs2607474 GG homozygote confers a significantly increased risk for age- and inflammation-related DAPK and CDH1 methylation in gastric epithelium. (PMID:23280118)
• HR signaling through cyclic AMP and exchange protein directly activated by cyclic AMP was required for the histamine effect on LPS-induced monocyte-derived dendritic cells responses (PMID:23465664)
• In this review, we focus on the role of histamine and its receptors in the treatment of Alzheimer’s disease. (PMID:23677734)
• But carriers of one or three copies of HRH1 (5% of individuals), HRH2 (1.1%) and HRH4 genes (0.9%) were also identified. (PMID:24236486)
• The inhibitory effects of histamine on reactive oxygen species production in whole blood phagocytes are caused by H2R rather than H4R histamine receptors. (PMID:24530738)
• upregulated on T regs following seasonal pollen exposure; allergen immunotherapy had no impact on the expression (PMID:24980224)
• Cimetidine reversed the exercise-induced improvement in learning and memory in rats. Central histamine H2 receptors play an important role in mediating the beneficial effects of forced exercise on learning and memory. (PMID:25192644)
• Thus, the results in the initial study were due to the degradation of histamine in skeletal muscle by ascorbate, because the histaminergic vasodilatation was unaffected by N-acetylcysteine. (PMID:25664905)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hrh2a	ENSDARG00000107444
mus_musculus	Hrh2	ENSMUSG00000034987
rattus_norvegicus	Hrh2	ENSRNOG00000018260

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

Histamine H2 receptor — P25021 (reviewed: P25021)

Alternative names: Gastric receptor I

All UniProt accessions (3): A0A1B0GTK7, A0A1B0GVZ0, P25021

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for histamine, primarily mediating gastric acid secretion. Predominantly expressed in the gastric mucosa, couples to G(s) G alpha proteins upon histamine binding, leading to activation of adenylate cyclase and increased intracellular cyclic AMP (cAMP) levels. This signaling cascade stimulates parietal cells to secrete hydrochloric acid, playing a key role in digestive physiology. Also expressed in other tissues, including the heart and central nervous system, where it may contribute to cardiac stimulation and modulate neurotransmitter release.

Subunit / interactions. Interacts with GNAS.

Subcellular location. Cell membrane.

Miscellaneous. Antagonists for this receptor have proven to be effective therapy for acid peptic disorders of the gastrointestinal tract. Certain antagonists are used in the treatment of neuropsychiatric and neurological diseases such as schizophrenia, Alzheimer disease and Parkinson disease.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P25021-1	1	yes
P25021-2	2

RefSeq proteins (4): NP_001124527, NP_001354640, NP_001380389, NP_001380390 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000503	Histamine_H2_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (47 total): helix 12, topological domain 8, transmembrane region 7, site 3, sequence variant 3, sequence conflict 3, compositionally biased region 2, turn 2, chain 1, region of interest 1, lipid moiety-binding region 1, glycosylation site 1, disulfide bond 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8YN3	ELECTRON MICROSCOPY	2.56
8YUT	ELECTRON MICROSCOPY	2.7
9IXJ	ELECTRON MICROSCOPY	2.92
8YN4	ELECTRON MICROSCOPY	2.97
7UL3	ELECTRON MICROSCOPY	3
8POK	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25021-F1	83.10	0.65

Antibody-complex structures (SAbDab): 6 — 7UL3, 8POK, 8YN3, 8YN4, 8YUT, 9IXJ

Functional residue map

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

Catalytic / active sites (3): 98 (essential for histamine binding); 186 (essential for tiotidine binding and implicated in h2 selectivity); 190 (implicated in histamine binding)

Post-translational modifications (1): 305

Disulfide bonds (1): 91–174

Glycosylation sites (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390650	Histamine receptors
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 123 (showing top): GOBP_DIGESTION, GOBP_ACID_SECRETION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_VASOCONSTRICTION, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SECRETION, GOBP_DIGESTIVE_SYSTEM_PROCESS, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_REGULATION_OF_VASOCONSTRICTION, GOCC_NEURON_PROJECTION, GOBP_VASCULAR_PROCESS_IN_CIRCULATORY_SYSTEM

GO Biological Process (8): gastric acid secretion (GO:0001696), immune response (GO:0006955), 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), chemical synaptic transmission (GO:0007268), positive regulation of vasoconstriction (GO:0045907), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): histamine receptor activity (GO:0004969), neurotransmitter receptor activity (GO:0030594), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (4): plasma membrane (GO:0005886), dendrite (GO:0030425), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Amine ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
digestive system process	1
acid secretion	1
immune system process	1
response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
anterograde trans-synaptic signaling	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of 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 receptor activity	1
signal transduction	1
G protein-coupled amine receptor activity	1
histamine binding	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HRH2	ATP12A	P54707	880
HRH2	ATP4A	P20648	880
HRH2	HDC	P19113	791
HRH2	GAST	P01350	732
HRH2	HRH3	Q9Y5N1	679
HRH2	IL13	P35225	611
HRH2	IL4	P05112	600
HRH2	HRH1	P35367	576
HRH2	IL3	P08700	572
HRH2	GNAQ	P50148	562
HRH2	PRKAA1	Q13131	544
HRH2	IFNG	P01579	527
HRH2	HNMT	P50135	488
HRH2	IL17A	Q16552	454
HRH2	H2BC21	Q16778	447

IntAct

6 interactions, top by confidence:

A	B	Type	Score
	HRH2	psi-mi:“MI:0915”(physical association)	0.400
HRH2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
HRH2	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HRH2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): HRH2 (Synthetic Lethality)

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: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
HRH2	“up-regulates activity”	GNAS	binding
HRH2	“up-regulates activity”	GNAL	binding
HRH2	“up-regulates activity”	GNAI1	binding
HRH2	“up-regulates activity”	GNAI3	binding
HRH2	“up-regulates activity”	GNAO1	binding
HRH2	“up-regulates activity”	GNAZ	binding
HRH2	“up-regulates activity”	GNAQ	binding
HRH2	“up-regulates activity”	GNA14	binding
histamine	“up-regulates activity”	HRH2	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:175683519:A:C	S96R	0.999
5:175683521:C:A	S96R	0.999
5:175683521:C:G	S96R	0.999
5:175683570:A:C	S113R	0.999
5:175683572:C:A	S113R	0.999
5:175683572:C:G	S113R	0.999
5:175683960:T:C	F243L	0.999
5:175683962:C:A	F243L	0.999
5:175683962:C:G	F243L	0.999
5:175683424:A:C	D64A	0.998
5:175683424:A:T	D64V	0.998
5:175683580:G:C	R116P	0.998
5:175683804:T:C	F191L	0.998
5:175683806:C:A	F191L	0.998
5:175683806:C:G	F191L	0.998
5:175683972:T:A	W247R	0.998
5:175683972:T:C	W247R	0.998
5:175683984:T:C	F251L	0.998
5:175683986:C:A	F251L	0.998
5:175683986:C:G	F251L	0.998
5:175684056:T:A	W275R	0.998
5:175684056:T:C	W275R	0.998
5:175684063:G:A	G277D	0.998
5:175683341:T:A	N36K	0.997
5:175683341:T:G	N36K	0.997
5:175683423:G:C	D64H	0.997
5:175683424:A:G	D64G	0.997
5:175683425:C:A	D64E	0.997
5:175683425:C:G	D64E	0.997
5:175683559:T:C	L109P	0.997

dbSNP variants (sampled 300 via entrez): RS1000044005 (5:175676118 C>T), RS1000142021 (5:175686391 A>G), RS1000146634 (5:175708111 TG>T), RS1000230301 (5:175665840 A>G), RS1000237198 (5:175691886 A>G), RS1000426518 (5:175689525 C>G), RS1000451673 (5:175695431 C>T), RS1000463552 (5:175679301 A>C), RS1000571353 (5:175690639 G>A), RS1000636720 (5:175685226 A>G), RS1000715566 (5:175679427 AG>A), RS1000756441 (5:175689727 G>A), RS1000810480 (5:175683162 A>C), RS1000828751 (5:175701664 C>T), RS1000831621 (5:175667225 C>A,T)

Disease associations

OMIM: gene MIM:142703 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_45	Night sleep phenotypes	5.000000e-06
GCST004863_109	Mosquito bite size	2.000000e-07
GCST007830_11	Anti-thyroid peroxidase (TPOAb) levels in Hashimoto’s thyroiditis	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008378	mosquito bite reaction size measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1941 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

115 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 336,663 (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
CHEMBL1000	CETIRIZINE	4	26,030
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1079	TIZANIDINE	4	12,099
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL1172	DESLORATADINE	4	19,720
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,220
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1201087	CABERGOLINE	4	12,778
CHEMBL1201203	BENZTROPINE	4	9,334
CHEMBL1201217	DYCLONINE	4	7,785
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL1201323	BETAZOLE	4	1,588
CHEMBL1201353	DEXCHLORPHENIRAMINE	4	8,566
CHEMBL1201356	METHYLERGONOVINE	4	3,335
CHEMBL1213351	PROPOXYPHENE	4	31,640
CHEMBL126224	IPRINDOLE	4
CHEMBL1282	IMIQUIMOD	4
CHEMBL134	CLONIDINE	4
CHEMBL1346	DARIFENACIN	4
CHEMBL1382	TOLTERODINE	4
CHEMBL1423	PIMOZIDE	4
CHEMBL142635	NAFTOPIDIL	4
CHEMBL1491	AMLODIPINE	4
CHEMBL1533310	HISTAMINE DIHYDROCHLORIDE	4
CHEMBL157101	KETOCONAZOLE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Histamine receptors

Most potent curated ligand interactions (23 total), top 23:

Ligand	Action	Affinity	Parameter
iodoaminopotentidine	Antagonist	9.2	pKi
[125I]iodoaminopotentidine	Antagonist	8.7	pKd
[3H]tiotidine	Antagonist	8.7	pKd
arpromidine	Full agonist	8.0	pKi
tiotidine	Antagonist	7.5	pKi
impromidine	Full agonist	7.2	pKi
ranitidine	Antagonist	7.1	pKi
oxo-arpromidine	Full agonist	7.0	pKi
cimetidine	Antagonist	6.85	pKi
amthamine	Full agonist	6.4	pEC50
UR-PG146	Full agonist	6.0	pKi
ST-1006	Agonist	6.0	pKi
JNJ-39758979	Antagonist	6.0	pKi
metiamide	Antagonist	5.8	pKi
burimamide	Full agonist	5.7	pEC50
INCB-38579	Antagonist	5.3	pKi
ABT-239	Inverse agonist	5.2	pKi
clobenpropit	Antagonist	5.2	pKi
ciproxifan	Antagonist	5.0	pKi
MK-0249	Antagonist	5.0	pKi
conessine	Antagonist	5.0	pKi
pitolisant	Antagonist	4.96	pKi
histamine	Full agonist	3.8	pKi

Binding affinities (BindingDB)

18 measured of 44 human assays (62 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_104911	KI	0.1 nM
CHEMBL2205813	KI	743 nM
SR 147778	KI	1000 nM
CHEMBL2429890	KI	1160 nM
CHEMBL2432046	KI	1480 nM
(R)-4-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)benzofuran-5-yl)benzonitrile	KI	1620 nM
CHEMBL2432051	KI	1730 nM
CHEMBL2432056	KI	1870 nM
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
NSC_0	KI	2560 nM
CHEMBL2432058	KI	3040 nM
CHEMBL2432045	KI	3470 nM
UR-AK68	KI	3500 nM
(12S,17S)-6-(piperazin-1-yl)-11-oxa-3,5-diazatetracyclo[8.7.0.0^{2,7}.0^{12,17}]heptadeca-1(10),2(7),3,5-tetraen-4-amine	KI	3550 nM
CHEMBL2432048	KI	3900 nM
GT 2228	KI	4470 nM
CHEMBL2432039	KI	6270 nM
CHEMBL2432062	KI	8520 nM

ChEMBL bioactivities

858 potent at pChembl≥5 of 1018 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.06	IC50	0.87	nM	CHEMBL194837
8.77	Ki	1.7	nM	CHEMBL1627
8.70	Ki	2	nM	CHEMBL5276441
8.69	Ki	2.042	nM	CHEMBL4875600
8.52	Ki	3.02	nM	CHEMBL5207281
8.48	EC50	3.311	nM	CHEMBL5206565
8.48	AC50	3.3	nM	DESLORATADINE
8.35	Ki	4.467	nM	CHEMBL4860528
8.35	Ki	4.5	nM	CHEMBL1090526
8.32	Ki	4.786	nM	CHEMBL5173079
8.31	EC50	4.898	nM	CHEMBL5178472
8.30	Ki	5.012	nM	CHEMBL5206565
8.29	Ki	5.129	nM	CHEMBL5200771
8.28	Ki	5.248	nM	CHEMBL5176229
8.24	Ki	5.754	nM	ASENAPINE MALEATE
8.24	Ki	5.7	nM	ASENAPINE MALEATE
8.24	EC50	5.754	nM	CHEMBL5207281
8.22	EC50	6.026	nM	CHEMBL5183205
8.22	EC50	6.026	nM	CHEMBL5200771
8.21	EC50	6.166	nM	CHEMBL2165642
8.21	Ki	6.166	nM	CHEMBL5208722
8.20	AC50	6.3	nM	FAMOTIDINE
8.19	Ki	6.457	nM	CHEMBL5180504
8.19	EC50	6.457	nM	CHEMBL1096431
8.13	EC50	7.413	nM	CHEMBL5092102
8.12	EC50	7.586	nM	CHEMBL2165628
8.12	EC50	7.586	nM	CHEMBL5094083
8.11	EC50	7.762	nM	CHEMBL2165632
8.09	Ki	8.128	nM	CHEMBL5184911
8.09	EC50	8.128	nM	CHEMBL5184911
8.03	EC50	9.333	nM	CHEMBL1094142
7.98	Ki	10.47	nM	CHEMBL4865965
7.97	EC50	10.72	nM	CHEMBL5204599
7.91	Kd	12.2	nM	HISTAMINE
7.91	Kd	12.2	nM	PRAMIPEXOLE
7.91	Kd	12.2	nM	CHEMBL5207281
7.91	Kd	12.2	nM	CHEMBL5183205
7.91	Kd	12.2	nM	CHEMBL5209081
7.91	Kd	12.2	nM	CHEMBL5204739
7.91	Kd	12.2	nM	CHEMBL5207206
7.91	Kd	12.2	nM	CHEMBL5200771
7.91	Kd	12.2	nM	CHEMBL5186770
7.91	Kd	12.2	nM	CHEMBL5189006
7.91	Kd	12.2	nM	CHEMBL5176780
7.91	Kd	12.2	nM	CHEMBL5170276
7.91	Kd	12.2	nM	CHEMBL5183015
7.91	Kd	12.2	nM	CHEMBL5209479
7.91	Kd	12.2	nM	CHEMBL5204599
7.91	Kd	12.2	nM	CHEMBL5205197
7.91	Kd	12.2	nM	CHEMBL5197548

PubChem BioAssay actives

673 with measured affinity, of 3405 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
2-(2,4-dichlorophenoxy)-N-[2-[2-(dimethylamino)ethoxy]-4-methylquinolin-6-yl]acetamide	254790: Inhibitory concentration against histamine H2 receptor	ic50	0.0009	uM
4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N-methyl-2,2-diphenylbutanamide	391601: Displacement of [3H]tiotidine from human histamine H2 receptor	ki	0.0017	uM
3-N-[2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethyl]-4-N-(3-phenylpropyl)-1,2,5-oxadiazole-3,4-diamine	1933286: Antagonist activity at histamine H2 receptor (unknown origin) assessed as inhibition constant	ki	0.0020	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-[1-(3-fluorophenyl)ethyl]urea	1756648: Displacement of [3H]UR-DE257 from human histamine H2 receptor expressed in sf9 insect cell membranes co-expressing GSalphaS incubated for 60 mins by microbeta scintillation counting method	ki	0.0020	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0030	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895211: Agonist activity at human histamine H2 receptor stably expressed in HEK293T cells co-expressing NlucN-mGs/hH2R-NlucC assessed as induction of mini-Gi protein recruitment using furimazine as substrate measured for 45 mins by luminescence assay	ec50	0.0033	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1756648: Displacement of [3H]UR-DE257 from human histamine H2 receptor expressed in sf9 insect cell membranes co-expressing GSalphaS incubated for 60 mins by microbeta scintillation counting method	ki	0.0045	uM
2-[6-fluoro-3-[(1R)-1-(3-methoxypyrazin-2-yl)ethyl]-1H-inden-2-yl]-N,N-dimethylethanamine	610139: Inhibition of H2 receptor	ki	0.0045	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[8-[[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]carbamoylamino]octyl]urea;tetrakis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0048	uM
1-[N’-[3-(2-amino-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895211: Agonist activity at human histamine H2 receptor stably expressed in HEK293T cells co-expressing NlucN-mGs/hH2R-NlucC assessed as induction of mini-Gi protein recruitment using furimazine as substrate measured for 45 mins by luminescence assay	ec50	0.0049	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-hexylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0051	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[6-[[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]carbamoylamino]hexyl]urea;tetrakis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0052	uM
(Z)-but-2-enedioic acid;9-chloro-4-methyl-13-oxa-4-azatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),7(12),8,10,14,16-hexaene	1063783: Displacement of [3H]Cimetidine from histamine H2 receptor (unknown origin)	ki	0.0057	uM
1-[N’-[3-(2-amino-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895211: Agonist activity at human histamine H2 receptor stably expressed in HEK293T cells co-expressing NlucN-mGs/hH2R-NlucC assessed as induction of mini-Gi protein recruitment using furimazine as substrate measured for 45 mins by luminescence assay	ec50	0.0060	uM
1-[N’-[3-(1H-imidazol-5-yl)propyl]carbamimidoyl]-3-[(1R)-1-phenylethyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0062	uM
N,N’-bis[N’-[3-(1H-imidazol-5-yl)propyl]carbamimidoyl]decanediamide	697893: Agonist activity at human H2R-Gsalphas expressed in Sf9 cells at 0.1 nM to 10 uM by steady state GTPase activity assay	ec50	0.0062	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0065	uM
(3S)-3-cyclohexyl-N-[N’-[3-(1H-imidazol-5-yl)propyl]carbamimidoyl]butanamide	478880: Agonist activity at GsalphaS-fused human histamine H2 receptor expressed in Sf9 cells by [35S]GTPgammaS binding assay	ec50	0.0065	uM
1-(8-aminooctyl)-3-[N’-[3-(1H-imidazol-5-yl)propyl]carbamimidoyl]urea	1830576: Agonist activity at human H2 receptor expressed in HEK293T-ARRB2 cells assessed as stimulation of beta-arrestin 2 recruitment	ec50	0.0074	uM
N-[1-(8-aminooctylamino)ethenyl]-N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]ethanimidamide	1830576: Agonist activity at human H2 receptor expressed in HEK293T-ARRB2 cells assessed as stimulation of beta-arrestin 2 recruitment	ec50	0.0076	uM
N’-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-N-[N’-[3-(1H-imidazol-5-yl)propyl]carbamimidoyl]decanediamide	697893: Agonist activity at human H2R-Gsalphas expressed in Sf9 cells at 0.1 nM to 10 uM by steady state GTPase activity assay	ec50	0.0076	uM
N,N’-bis[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]decanediamide	697893: Agonist activity at human H2R-Gsalphas expressed in Sf9 cells at 0.1 nM to 10 uM by steady state GTPase activity assay	ec50	0.0078	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-[1-(3-fluorophenyl)ethyl]urea;dihydrochloride	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	ki	0.0081	uM
N-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-cyclohexylbutanamide	478880: Agonist activity at GsalphaS-fused human histamine H2 receptor expressed in Sf9 cells by [35S]GTPgammaS binding assay	ec50	0.0093	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-(furan-2-ylmethyl)urea	1756648: Displacement of [3H]UR-DE257 from human histamine H2 receptor expressed in sf9 insect cell membranes co-expressing GSalphaS incubated for 60 mins by microbeta scintillation counting method	ki	0.0105	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-(2-cyclohexylpropyl)urea;bis(2,2,2-trifluoroacetic acid)	1895211: Agonist activity at human histamine H2 receptor stably expressed in HEK293T cells co-expressing NlucN-mGs/hH2R-NlucC assessed as induction of mini-Gi protein recruitment using furimazine as substrate measured for 45 mins by luminescence assay	ec50	0.0107	uM
Pramipexole	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[4-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-cyclohexylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[4-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-[6-[[N’-[4-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]carbamoylamino]hexyl]urea;tetrakis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-(2-methyl-5-phenylpentyl)urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[4-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-(8-aminooctyl)-3-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]urea;tris(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-benzyl-3-[N’-[3-(5-methyl-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]urea;2,2,2-trifluoroacetic acid	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-[6-[[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]carbamoylamino]hexyl]urea;tetrakis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[(2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-[4-[(dimethylamino)methyl]triazol-1-yl]propyl]carbamimidoyl]-3-[(1R)-1-phenylethyl]urea;tris(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-(8-aminooctyl)-3-[N’-[3-(5-methyl-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(5-amino-1,3,4-oxadiazol-2-yl)propyl]carbamimidoyl]-3-hexylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-4-methyl-1,3-oxazol-5-yl)propyl]carbamimidoyl]-3-(2-cyclohexylpropyl)urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(5-methyl-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;2,2,2-trifluoroacetic acid	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[(2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methyl]carbamimidoyl]-3-(2-methyl-5-phenylpentyl)urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-4-methyl-1,3-oxazol-5-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[4-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-(2-methyl-5-phenylpentyl)urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-(2-methyl-5-phenylpentyl)urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(5-amino-1,3,4-oxadiazol-2-yl)propyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)phenyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM
1-[N’-[(2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)methyl]carbamimidoyl]-3-[2-methyl-3-(4-methylphenyl)propyl]urea;bis(2,2,2-trifluoroacetic acid)	1895194: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis	kd	0.0122	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Histamine	increases activity, affects cotreatment, decreases response to substance, decreases expression, affects localization (+9 more)	11
Ranitidine	affects response to substance, decreases reaction, affects binding, decreases activity	9
Cimetidine	increases expression, affects binding, decreases reaction, affects cotreatment, affects response to substance (+5 more)	8
Famotidine	increases activity, increases expression, affects binding, decreases activity, affects response to substance (+1 more)	4
tiotidine	increases activity, decreases expression, increases expression, affects binding, decreases reaction (+1 more)	3
Cyclic AMP	increases abundance, increases activity, increases reaction, decreases reaction, decreases expression (+3 more)	3
Dimaprit	increases expression, affects binding, increases activity, affects expression, increases abundance (+2 more)	3
Lipopolysaccharides	decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment	2
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
4-methylhistamine	increases activity, affects expression, affects binding	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
N-methylhistamine	affects binding, increases activity	1
amthamine	affects binding, increases activity	1
clobenpropit	increases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Asbestos	increases expression	1
Benzo(a)pyrene	affects methylation	1
Burimamide	decreases abundance, decreases reaction, increases abundance, increases expression, affects binding (+2 more)	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Colforsin	increases reaction, decreases reaction, increases abundance	1
Metformin	affects binding, affects response to substance, decreases activity	1
Oxygen	affects cotreatment, decreases activity, decreases response to substance, affects binding	1
Parathion	increases methylation	1
Promethazine	affects binding, decreases activity	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1

ChEMBL screening assays

508 unique, capped per target: 430 binding, 73 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000175	Binding	Binding affinity to histamine H2 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1104101	Functional	Agonist activity at human histamine H2 receptor expressed in Sf9 cells coexpressing GsalphaS protein by steady-state GTPase assay	Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists. — J Med Chem
CHEMBL4039797	ADMET	Displacement of [3H]Cimetidine from human H2 receptor expressed in HEK cell membranes after 90 mins by scintillation counting method	Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 spontaneously immortalized cell line, 1 cancer cell line, 1 undefined cell line type, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7RG	Ubigene A-549 HRH2 KO	Cancer cell line	Male
CVCL_H448	CHO-K1/H2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV36	cAMP Hunter CHO-K1 HRH2 Gs/Gq	Spontaneously immortalized cell line	Female
CVCL_KX84	PathHunter CHO-K1 HRH2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_RU12	Chem-2 HRH2	Undefined cell line type
CVCL_U012	CHO-HRH2	Spontaneously immortalized cell line	Female
CVCL_ZK70	GeneBLAzer H2-CRE-bla HEK 293T	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis