TRPA1

Summary

TRPA1 (transient receptor potential cation channel subfamily A member 1, HGNC:497) is a protein-coding gene on chromosome 8q21.11, encoding Transient receptor potential cation channel subfamily A member 1 (O75762). Ligand-activated Ca(2+)-permeable, nonselective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function.

The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control.

Source: NCBI Gene 8989 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial episodic pain syndrome with predominantly upper body involvement (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 101 total
• Phenotypes (HPO): 3
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007332

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:497
Approved symbol	TRPA1
Name	transient receptor potential cation channel subfamily A member 1
Location	8q21.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104321
Ensembl biotype	protein_coding
OMIM	604775
Entrez	8989

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000262209, ENST00000519720, ENST00000520596, ENST00000520788, ENST00000522271, ENST00000523582, ENST00000859810

RefSeq mRNA: 1 — MANE Select: NM_007332 NM_007332

CCDS: CCDS34908

Canonical transcript exons

ENST00000262209 — 27 exons

Exon	Start	End
ENSE00000697467	72023814	72023911
ENSE00000697468	72025960	72026073
ENSE00000697469	72029901	72029969
ENSE00000697470	72033644	72033826
ENSE00000697471	72034248	72034377
ENSE00000697479	72046513	72046608
ENSE00000697482	72047148	72047207
ENSE00000697483	72050778	72050871
ENSE00000697484	72052599	72052765
ENSE00000697486	72053753	72053867
ENSE00000697488	72055436	72055600
ENSE00000697492	72056917	72057017
ENSE00000697494	72057717	72057816
ENSE00000980807	72071711	72071867
ENSE00000980808	72069023	72069198
ENSE00000980809	72065451	72065558
ENSE00000980810	72063463	72063571
ENSE00000980811	72062799	72062944
ENSE00001139526	72055686	72055855
ENSE00001182379	72021250	72023116
ENSE00001182388	72075299	72075584
ENSE00001505488	72059390	72059438
ENSE00001505489	72061625	72061761
ENSE00003465735	72037983	72038072
ENSE00003497688	72039727	72039797
ENSE00003527095	72036288	72036457
ENSE00003692711	72038865	72039027

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 95.95.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5382 / max 226.4786, expressed in 218 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93577	1.5382	218

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.95	gold quality
secondary oocyte	CL:0000655	95.92	gold quality
mucosa of urinary bladder	UBERON:0001259	93.74	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.50	gold quality
rectum	UBERON:0001052	84.01	gold quality
ileal mucosa	UBERON:0000331	83.61	gold quality
colonic epithelium	UBERON:0000397	81.68	gold quality
colonic mucosa	UBERON:0000317	81.58	gold quality
urinary bladder	UBERON:0001255	78.83	gold quality
jejunal mucosa	UBERON:0000399	78.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.21	gold quality
mucosa of transverse colon	UBERON:0004991	77.10	gold quality
stromal cell of endometrium	CL:0002255	76.86	gold quality
small intestine	UBERON:0002108	75.66	gold quality
duodenum	UBERON:0002114	75.55	gold quality
transverse colon	UBERON:0001157	74.62	gold quality
germinal epithelium of ovary	UBERON:0001304	74.48	silver quality
body of stomach	UBERON:0001161	72.72	gold quality
gall bladder	UBERON:0002110	72.65	gold quality
caecum	UBERON:0001153	72.38	gold quality
pylorus	UBERON:0001166	72.29	silver quality
stomach	UBERON:0000945	72.26	gold quality
vermiform appendix	UBERON:0001154	71.66	gold quality
trigeminal ganglion	UBERON:0001675	70.74	gold quality
intestine	UBERON:0000160	70.14	gold quality
large intestine	UBERON:0000059	68.35	gold quality
colon	UBERON:0001155	67.65	gold quality
fundus of stomach	UBERON:0001160	65.37	gold quality
cardia of stomach	UBERON:0001162	64.66	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting TRPA1, 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-656-3P	100.00	72.15	2788
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-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4495	99.82	72.08	3080

Literature-anchored findings (GeneRIF, showing 40)

• cellular and molecular target for the pungent action of mustard oils; support an emerging role for TRP channel ANKTM1 as an ionotropic cannabinoid receptor (PMID:14712238)
• TRPA1 is a novel substrate for the de-ubiquitinating activity of CYLD, and this de-ubiquitination has the net effect of increasing the cellular pool of TRPA1 proteins. (PMID:16500080)
• Thiol reactive compounds of diverse structure activate TRPA1 in a manner that relies on covalent modification of cysteine residues within the cytoplasmic N terminus of the channel. (PMID:17164327)
• TRPA1 is well conserved across the animal kingdom, with likely orthologs from human to nematode, which suggest an ancestral role for this channel, probably in sensation–{REVIEW} (PMID:17217068)
• TRPA1 is activated by the insecticide and natural toxin allyl isothiocyanate which is known as insecticide. (PMID:17285310)
• trypsin or tryptase released in response to tissue inflammation might trigger the sensation of pain by TRPA1 activation (PMID:17571167)
• TRPA1 in the bladder epithelium might be involved in the bladder sensory transduction and the induction process of overactive bladder by BOO. (PMID:18384850)
• In patients suffering from cold allodynia following cold injury, no evidence is found for sensitization of TRPA1 or TRPM8 or pathologic expression of TRPM8 on silent afferent C-fiber nociceptors. (PMID:18440147)
• While TRPA1 localisation is more widespread than TRPV1, it represents a promising novel drug target for the treatment of chronic pain and hypersensitivity. (PMID:18456404)
• Our findings reveal a molecular basis of species-specific channel gating and provide novel insights into how TRPA1 respond to stimuli. (PMID:18463259)
• The results of this study support the hypothesis that 4-ONE is a relevant endogenous activator of vagal C-fibres via an interaction with TRPA1, and at less relevant concentrations, it may activate nerves via TRPV1. (PMID:18499726)
• TRPA1 is required for sensitivity of cultured dorsal root ganglion neurons to 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2). (PMID:18671867)
• TRPA1 channels are targeted by an array of inflammatory mediators to elicit inflammatory pain in the nervous system (PMID:18769139)
• TRPA1 is potentiated and inactivated by permeating calcium ions (PMID:18775987)
• TRPA1 plays an important role in the mechanisms responsible for mechanical hypersensitivity observed in inflammatory and neuropathic pain models (PMID:18954467)
• Caffeine does not activate human TRPA1; instead, it suppresses its activity. (PMID:18988737)
• Toluene diisocyanate causes sensory nerve activation and airway sensory irritation via the activation of the ion channel, TRPA1 (PMID:19059884)
• New studies have revealed an essential role for TRPA1, a sensory neuronal TRP ion channel, in airway chemosensation and inflammation–{REVIEW} (PMID:19074743)
• Pore dilation occurs in TRPA1, but not in TRPM8 channels. (PMID:19159452)
• TRPA1 acts as a sensor molecule for enterochromaffin cells and may regulate gastrointestinal function (PMID:19211797)
• The ligand-specific gating mechanisms of Trpa1 are summarized and discussd. (PMID:19237591)
• Study provides evidence that TRPA1 is broadly expressed in the skin and may directly be involved in the regulation of keratinocyte differentiation as well as of inflammatory responses. (PMID:19282836)
• Transient receptor potential ankyrin 1 (TRPA1) modulates mechanotransduction via a cell-autonomous mechanism in nociceptor terminals to modify their mechanical firing properties. (PMID:19369549)
• QGP-1 cells, a human pancreatic endocrine cell line, were found to highly express TRPA1 and enterochromaffin cell marker genes. (PMID:19507004)
• mRNA for TRPA1 and TRPM8 are strongly upregulated in differentiating IMR-32 cells. (PMID:19507192)
• These data show that TRPA1 is expressed in lingual nerve neuromas, but, it appears that, at this site, TRPA1 does not play a principal role in the development of neuropathic pain. (PMID:19715741)
• Alkaline pH causes pain sensation through activation of TRPA1. (PMID:20190512)
• TRPA1 ion channels: a gateway to airway irritation and reflex responses induced by inhaled oxidants. (PMID:20194132)
• Prolonged agonist application can evoke uptake of large dye molecules in TRPA1 expressing cells. (PMID:20457836)
• Enhanced channel activity associated with the asparagine855serine point mutation is consistent with the pathological states observed in patients with familial episodic pain syndrome. (PMID:20547126)
• identify basic residues in the C-terminus that are strongly involved in TRPA1 voltage and chemical sensitivity, and some of them may represent possible interaction sites for negatively charged molecules that are generally considered to modulate TRPA1. (PMID:20946100)
• TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids. (PMID:21094256)
• Introduction of a Met268Pro point mutation into mTRPA1 changed the effect of caffeine from activation to suppression. (PMID:21112285)
• upregulating endogenous expression of TRPA1, that TRPA1 activation may be an additional trigger for co-expressed calcium-dependent ion channels such as TRPM5, and that TRPM5 may amplify responses to TRPA1 ligands (PMID:21133676)
• Cultured and native human odontoblasts express functional TRPA1 channels that may play a crucial role in mediating thermal sensation in teeth. (PMID:21168271)
• Findings provide important insight into the basic fundamental properties and function of TRPA1 channels in general and hTRPA1 channel in particular. (PMID:21195050)
• Human dental pulp fibroblasts express TRPA1 at the molecular, protein, and functional levels, indicating a possible role for fibroblasts in mediating cold responses in human teeth. (PMID:21419293)
• TRPA1 SNPs are associated with menthol preference among smokers. (PMID:21719896)
• Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. (PMID:21848366)
• Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli (PMID:21930928)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpa1a	ENSDARG00000016699
danio_rerio	trpa1b	ENSDARG00000031875
mus_musculus	Trpa1	ENSMUSG00000032769
rattus_norvegicus	Trpa1	ENSRNOG00000007354
drosophila_melanogaster	TrpA1	FBGN0035934
caenorhabditis_elegans	trpa-2	WBGENE00010873

Protein

Protein identifiers

Transient receptor potential cation channel subfamily A member 1 — O75762 (reviewed: O75762)

Alternative names: Ankyrin-like with transmembrane domains protein 1, Transformation-sensitive protein p120, Wasabi receptor

All UniProt accessions (2): O75762, H0YAW0

UniProt curated annotations — full annotation on UniProt →

Function. Ligand-activated Ca(2+)-permeable, nonselective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function. Has a relatively high Ca(2+) selectivity, with a preference for divalent over monovalent cations (Ca(2+) > Ba(2+) > Mg(2+) > NH4(+) > Li(+) > K(+)), the influx of cation into the cytoplasm leads to membrane depolarization. Has a central role in the pain response to endogenous inflammatory mediators, such as bradykinin and to a diverse array of irritants. Activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an environmental irritant. Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner. Non-electrophile agonists bind at distinct sites in the transmembrane domain to promote channel activation. Also acts as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds.

Subunit / interactions. Homotetramer. Interacts with TMEM100. Interacts with EGLN1. Interacts with the scorpion wasabi receptor toxin at the same site that electrophiles but in a non-covalent manner.

Subcellular location. Cell membrane.

Post-translational modifications. TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain. Hydroxylation is required for TRPA1 activity inhibition in normoxia. In hypoxia, the decrease in oxygen concentration diminishes the activity of the hydroxylase EGLN1, thus relieving TRPA1 from inhibition and ultimately leading to channel activation. Oxidation of Cys-633 and Cys-856 in hyperoxia may override the hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation.

Disease relevance. Episodic pain syndrome, familial, 1 (FEPS1) [MIM:615040] An autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress. The period of intense pain is accompanied by breathing difficulties, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall. Affected individuals do not manifest altered pain sensitivity outside the episodes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Electrophilic ligands activate the channel by covalent modification of intracellular cysteines; Cys-621 plays a key role in covalent binding of electrophiles. Extracellular Ca(2+) both potentiates and inactivates TRPA1; a rapid potentiation follows by slow desensitization. Activated by increase in intracellular Ca(2+) concentration. Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079, AP-18, HC-030031, and aryl sulfonamide derivative (S)-N-(4-chlorobenzyl)-1-((4-fluorophenyl)sulfonyl)pyrrolidine-2-carboxamide (ASD). Activated by benzyl isothiocyanate (BITC), iodoacetamide, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), N-ethylmaleimide (NEM), and 2-aminoethyldiphenylborinate (2-APB). Also activated by hyperoxia. Acivated by intracellular Zn(2+). TRPA1 activation may critically depend on the presence of small intracellular compounds such as polyphosphates.

Domain organisation. C-terminal helices from the four subunits associate to form atypical coiled coil structure; this region is probably involved in binding the inositol polyphosphates that are required for optimal channel activity (in vitro). The ANK repeat domain consists of a convex stem structure formed by five ANK repeats and 11 additional ANK repeats that form a crescent-shaped structure that surrounds the protein core.

Similarity. Belongs to the transient receptor (TC 1.A.4) family.

RefSeq proteins (1): NP_015628* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR005821	Ion_trans_dom	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR052076	TRP_cation_channel	Family

Pfam: PF00023, PF00520, PF12796, PF13637

Catalyzed reactions (Rhea), 5 shown:

• Zn(2+)(in) = Zn(2+)(out) (RHEA:29351)
• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (144 total): helix 35, mutagenesis site 19, strand 17, repeat 16, binding site 11, topological domain 8, site 7, transmembrane region 6, turn 6, sequence variant 6, disulfide bond 5, modified residue 3, glycosylation site 2, chain 1, intramembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
6HC8	X-RAY DIFFRACTION	1.9
6V9V	ELECTRON MICROSCOPY	2.6
7OR0	ELECTRON MICROSCOPY	2.64
7OR1	ELECTRON MICROSCOPY	2.64
9MOE	ELECTRON MICROSCOPY	2.7
6PQQ	ELECTRON MICROSCOPY	2.81
6PQO	ELECTRON MICROSCOPY	2.88
6X2J	ELECTRON MICROSCOPY	3
7JUP	ELECTRON MICROSCOPY	3.05
6PQP	ELECTRON MICROSCOPY	3.06
6V9W	ELECTRON MICROSCOPY	3.1
9M8S	ELECTRON MICROSCOPY	3.1
6V9X	ELECTRON MICROSCOPY	3.3
6V9Y	ELECTRON MICROSCOPY	3.6
6WJ5	ELECTRON MICROSCOPY	3.6
9M8N	ELECTRON MICROSCOPY	3.81
3J9P	ELECTRON MICROSCOPY	4.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75762-F1	81.75	0.35

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 (7): 620 (required for c-621 reactivity); 621 (essential for electrophile activation. sensor for electrophilic agents); 622 (key residue for activation by the scorpion wasabi receptor toxin); 634 (important residue for activation by the scorpion wasabi receptor toxin); 646 (important residue for activation by the scorpion wasabi receptor toxin); 665 (important for electrophile activation); 915 (crucial for calcium permeation)

Ligand- & substrate-binding residues (11): 414 (covalent); 421 (covalent); 621 (covalent; cys highly reactive); 641 (covalent); 665 (covalent); 710 (covalent); 788; 791; 805; 808; 1046–1052

Post-translational modifications (3): 394, 633, 856

Disulfide bonds (5): 192–665, 462–665, 608–621, 621–665, 633–856

Glycosylation sites (2): 747, 753

Mutagenesis-validated functional residues (19):

Position	Phenotype
173	decrease in activation by hyperoxia and diallyl disulfide.
192	decrease in activation by hyperoxia and diallyl disulfide.
394	loss of answer to hypoxia and hydroxylase inhibitor dmog, but not to aitc and hyperoxia.
620	important decrease in electrophile-evoked response.
621	do not exhibit detectable current upon electrophile stimulation. no change in answer to hyperoxia and diallyl disulfide.
622	loss of activation by the scorpion wasabi receptor toxin.
633	decrease in activation by hyperoxia and diallyl disulfide. important decrease in activation by hyperoxia and diallyl dis
634	loss of activation by the scorpion wasabi receptor toxin.
641	decrease in electrophile-evoked and hyperoxia response.
641	does not affect activation by electrophiles.
646	loss of activation by the scorpion wasabi receptor toxin.
665	decrease in electrophile-evoked and hyperoxia response. does not affect covalent agonist bitc electrophile-evoked.
788	lacks calcium-mediated potentiation but retains calcium-mediated desensitization. lacks calcium-mediated potentiation an
791	lacks calcium-mediated potentiation and lacks desensitization; when associated with s-788 and s-805.
805	lacks calcium-mediated potentiation and lacks desensitization; when associated with s-788 and s-791.
856	decrease in activation by hyperoxia and diallyl disulfide. important decrease in activation by hyperoxia and diallyl dis
909	loss of inhibition by a-967079, ap-18, and asd. increase in activation by cinnamaldehyde, aitc and acrolein.
915	abolishes zinc influx. abolishes activation by extracellular but not by intracellular zinc.
944	loss of inhibition by a-967079, ap-18, and asd. weak or no change in activation by cinnamaldehyde, aitc and acrolein.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 229 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_RESPONSE_TO_COLD, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_RESPONSE_TO_FOOD, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (34): monoatomic ion transport (GO:0006811), intracellular calcium ion homeostasis (GO:0006874), cell surface receptor signaling pathway (GO:0007166), response to cold (GO:0009409), response to xenobiotic stimulus (GO:0009410), urinary bladder smooth muscle contraction (GO:0014832), sensory perception of pain (GO:0019233), cellular response to heat (GO:0034605), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), response to pain (GO:0048265), thermoception (GO:0050955), detection of mechanical stimulus involved in sensory perception of pain (GO:0050966), detection of chemical stimulus involved in sensory perception of pain (GO:0050968), protein homotetramerization (GO:0051289), cellular response to hydrogen peroxide (GO:0070301), cellular response to cold (GO:0070417), calcium ion transmembrane transport (GO:0070588), cellular response to food (GO:0071240), cellular response to carbon dioxide (GO:0071244), cellular response to caffeine (GO:0071313), cellular response to toxic substance (GO:0097237), calcium ion transmembrane import into cytosol (GO:0097553), regulation of neuronal action potential (GO:0098908), regulation of blood circulation (GO:1903522), positive regulation of monoatomic anion transport (GO:1903793), system process (GO:0003008), calcium ion transport (GO:0006816), calcium-mediated signaling (GO:0019722), cellular response to stress (GO:0033554), monoatomic ion transmembrane transport (GO:0034220), response to hydrogen peroxide (GO:0042542), detection of mechanical stimulus involved in sensory perception (GO:0050974), transmembrane transport (GO:0055085), cellular response to oxygen-containing compound (GO:1901701)

GO Molecular Function (10): voltage-gated calcium channel activity (GO:0005245), calcium channel activity (GO:0005262), channel activity (GO:0015267), intracellularly gated calcium channel activity (GO:0015278), identical protein binding (GO:0042802), temperature-gated cation channel activity (GO:0097604), osmolarity-sensing monoatomic cation channel activity (GO:1990760), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), gated channel activity (GO:0022836)

GO Cellular Component (5): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), axon (GO:0030424), stereocilium bundle (GO:0032421), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Stimuli-sensing channels	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation channel activity	3
cellular response to stress	2
sensory perception of pain	2
channel activity	2
transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
signal transduction	1
response to stress	1
response to temperature stimulus	1
response to chemical	1
urinary tract smooth muscle contraction	1
sensory perception	1
response to heat	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
multicellular organismal response to stress	1
sensory perception of temperature stimulus	1
detection of mechanical stimulus involved in sensory perception	1
detection of chemical stimulus involved in sensory perception	1
protein homooligomerization	1
protein tetramerization	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to cold	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
response to food	1
cellular response to chemical stimulus	1
response to carbon dioxide	1
cellular response to oxygen-containing compound	1
response to caffeine	1
cellular response to alkaloid	1
cellular response to purine-containing compound	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
passive transmembrane transporter activity	1
intracellularly ligand-gated monoatomic ion channel activity	1

Protein interactions and networks

STRING

2436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPA1	TRPV1	Q8NER1	992
TRPA1	TRPM8	Q7Z2W7	984
TRPA1	KNG1	P01042	926
TRPA1	NGF	P01138	916
TRPA1	TRPV2	Q9Y5S1	896
TRPA1	TRPM3	Q9HCF6	813
TRPA1	SCG3	Q8WXD2	807
TRPA1	TAC1	P20366	787
TRPA1	F2RL1	P55085	779
TRPA1	TRPC5	Q9UL62	776
TRPA1	TRPC1	P48995	771
TRPA1	TRPC3	Q13507	768
TRPA1	TRPC4	Q9UBN4	768
TRPA1	TRPM4	Q8TD43	767
TRPA1	CALML3	P27482	752
TRPA1	CALML5	Q9NZT1	752

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TRPA1	TRPA1	psi-mi:“MI:0407”(direct interaction)	0.520
TRPA1	HUWE1	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): AKAP5 (Affinity Capture-Western), TRPA1 (Affinity Capture-Western), HUWE1 (Proximity Label-MS), TRPA1 (Proximity Label-MS), TRPA1 (Affinity Capture-MS), TRPA1 (Affinity Capture-MS), TRPA1 (Cross-Linking-MS (XL-MS)), TRPA1 (Cross-Linking-MS (XL-MS)), TRPA1 (Affinity Capture-Western)

ESM2 similar proteins: B2RXR6, O15084, O75762, O75832, P0C6P7, Q08DV6, Q0P5B9, Q14DN9, Q3SX45, Q3V096, Q495B1, Q502K3, Q505D1, Q53RE8, Q5F478, Q5RCK5, Q5U2S6, Q5ZIJ9, Q5ZLC8, Q5ZM55, Q6GNY1, Q6GPE5, Q6RI86, Q7Z020, Q804S5, Q80SY4, Q810B6, Q86YT6, Q8BLA8, Q8BTI7, Q8HXA6, Q8N8A2, Q8N9B4, Q8NB46, Q8VHS6, Q8WXK1, Q91ZU0, Q96Q27, Q9BGT9, Q9D2X0

Diamond homologs: A2AQH4, A2AS55, A6QR20, O04251, O75762, O90760, P25963, Q10311, Q1RJM6, Q24145, Q499M5, Q4JHE0, Q5H9F3, Q6RI86, Q70X92, Q86WC6, Q8BLA8, Q8N8A2, Q8R3P9, Q9BQI6, Q9J4Z4, Q9WV72, Q9Y575, Q9Z2F6, A2ARS0, B2RXR6, C9JTQ0, L7XCU0, L7XDS4, O15084, O89019, P25799, Q00653, Q18297, Q2TB02, Q3EC11, Q3KP44, Q3SX00, Q4ULZ2, Q502K3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	26
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

3916 predictions. Top by Δscore:

Variant	Effect	Δscore
8:72023882:CCCAG:C	acceptor_gain	1.0000
8:72023883:CCAG:C	acceptor_gain	1.0000
8:72023884:CAG:C	acceptor_gain	1.0000
8:72023886:G:GC	acceptor_gain	1.0000
8:72034242:TCTTA:T	donor_loss	1.0000
8:72034243:CTTA:C	donor_loss	1.0000
8:72034244:TTA:T	donor_loss	1.0000
8:72034245:TA:T	donor_loss	1.0000
8:72034246:ACCTG:A	donor_loss	1.0000
8:72036453:CTTTT:C	acceptor_gain	1.0000
8:72036457:TC:T	acceptor_loss	1.0000
8:72036458:C:CC	acceptor_gain	1.0000
8:72036463:A:AC	acceptor_gain	1.0000
8:72036463:A:C	acceptor_gain	1.0000
8:72038860:ATTAC:A	donor_loss	1.0000
8:72038861:TTAC:T	donor_loss	1.0000
8:72038862:TACC:T	donor_loss	1.0000
8:72038863:ACC:A	donor_loss	1.0000
8:72039718:AATAC:A	donor_gain	1.0000
8:72046505:GAACT:G	donor_loss	1.0000
8:72046506:AACTT:A	donor_loss	1.0000
8:72046507:ACT:A	donor_loss	1.0000
8:72046508:CTTA:C	donor_loss	1.0000
8:72046509:TTA:T	donor_loss	1.0000
8:72046510:TAC:T	donor_loss	1.0000
8:72046511:A:AC	donor_gain	1.0000
8:72046511:A:C	donor_loss	1.0000
8:72046512:C:CA	donor_gain	1.0000
8:72046512:C:G	donor_loss	1.0000
8:72046512:CG:C	donor_gain	1.0000

AlphaMissense

7520 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:72055592:C:G	R458P	0.998
8:72055689:G:T	A454D	0.998
8:72052746:G:T	A555D	0.997
8:72055497:C:G	A490P	0.997
8:72055499:G:T	A489E	0.997
8:72061733:G:T	A279D	0.997
8:72053835:G:T	A521E	0.996
8:72055500:C:G	A489P	0.996
8:72055595:C:A	G457V	0.996
8:72055595:C:T	G457E	0.996
8:72055596:C:A	G457W	0.996
8:72055692:G:T	A453E	0.996
8:72057764:G:T	A349E	0.996
8:72057765:C:G	A349P	0.996
8:72057782:C:G	R343P	0.996
8:72029927:C:G	A971P	0.995
8:72029966:C:G	G958R	0.995
8:72036418:A:G	W809R	0.995
8:72036418:A:T	W809R	0.995
8:72039729:T:A	K710N	0.995
8:72039729:T:G	K710N	0.995
8:72039778:C:G	R694P	0.995
8:72053836:C:G	A521P	0.995
8:72055463:A:G	L501P	0.995
8:72055511:G:T	P485H	0.995
8:72055690:C:G	A454P	0.995
8:72056997:C:G	D372H	0.995
8:72057728:A:G	L361P	0.995
8:72023066:A:G	L1067P	0.994
8:72029909:C:G	A977P	0.994

dbSNP variants (sampled 300 via entrez): RS1000004224 (8:72071579 C>A,G,T), RS1000025831 (8:72030857 C>G), RS1000089152 (8:72036327 A>G), RS1000109550 (8:72035263 A>C), RS1000118065 (8:72035010 G>A), RS1000126715 (8:72078649 A>G), RS1000158355 (8:72034837 C>T), RS1000166855 (8:72083789 C>T), RS1000185643 (8:72077123 T>G), RS1000227712 (8:72053433 C>A,G,T), RS1000362423 (8:72041478 A>T), RS1000371856 (8:72048257 C>A,T), RS1000386047 (8:72067063 T>C), RS1000415266 (8:72029119 C>G), RS1000418324 (8:72089520 C>A)

Disease associations

OMIM: gene MIM:604775 | disease phenotypes: MIM:615040

GenCC curated gene-disease

Disease	Classification	Inheritance
familial episodic pain syndrome with predominantly upper body involvement	Moderate	Autosomal dominant
hereditary peripheral neuropathy	Limited	Autosomal dominant

Mondo (2): familial episodic pain syndrome with predominantly upper body involvement (MONDO:0014021), hereditary peripheral neuropathy (MONDO:0020127)

Orphanet (2): Familial episodic pain syndrome (Orphanet:391384), Familial episodic pain syndrome with predominantly upper body involvement (Orphanet:391389)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0003593	Infantile onset
HP:0032148	Episodic pain

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001356_8	Gout	1.000000e-07
GCST003470_6	Coronary artery disease	5.000000e-13
GCST003471_6	Myocardial infarction	3.000000e-06
GCST003833_12	Adult asthma	3.000000e-06
GCST004749_26	Lung cancer in ever smokers	7.000000e-06
GCST005956_46	Waist-to-hip ratio adjusted for BMI	3.000000e-07
GCST005962_26	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST009391_1706	Metabolite levels	5.000000e-06
GCST009391_244	Metabolite levels	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010340	cholesteryl ester 14:0 measurement
EFO:0010494	guanosine diphosphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6007 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,031,176 (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
CHEMBL139	DICLOFENAC	4	125,009
CHEMBL256087	MENTHOL	4	182,803
CHEMBL3	NICOTINE	4	184,969
CHEMBL686	MEFENAMIC ACID	4	61,835
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL165	RESVERATROL	3	60,144
CHEMBL258405	ICILLIN	3	1,025
CHEMBL470670	LEVOMENTHOL	3	182,553
CHEMBL74415	CANNABINOL	3	18,794
CHEMBL23293	SALIRASIB	2	450
CHEMBL23588	FLUFENAMIC ACID	2	34,797
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884
CHEMBL2387742	CANNABIDIVARIN	2	4,963
CHEMBL281202	CARVACROL	2	24,196
CHEMBL29411	THYMOL	2	69,226
CHEMBL356479	CHLORDANTOIN	2	2,181
CHEMBL359965	ALLICIN	2	14,806
CHEMBL417799	SANGUINARIUM	2	8,822
CHEMBL497318	CANNABIGEROL	2	11,097
CHEMBL5940975	RG6341	2	11
CHEMBL184238	URB-597	1
CHEMBL233248	ALLYL ISOTHIOCYANATE	1
CHEMBL295316	PLUMBAGIN	1

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs920829	TRPA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (78 total), top 25:

Ligand	Action	Affinity	Parameter
JT010	Activation	9.19	pEC50
GDC-0334	Inhibition	8.77	pIC50
resolvin D2	Inhibition	8.7	pIC50
nedizantrep	Inhibition	8.03	pIC50
AM-0902	Antagonist	7.7	pIC50
PF-4840154	Activation	7.6	pEC50
cannabichromene	Agonist	7.22	pEC50
resolvin D1	Inhibition	7.2	pIC50
dibenzoxazepine	Activation	7.2	pEC50
A-967079	Inhibition	7.2	pIC50
morphanthridine	Activation	7.1	pEC50
Gd3+	Antagonist	7.0	pIC50
1’-acetoxychavicol acetate	Activation	6.8	pEC50
chloropicrin	Activation	6.7	pEC50
chlorobenzylidene malononitrile	Activation	6.7	pEC50
omega-chloroacetophenone	Activation	6.6	pEC50
NPPB	Activation	6.49	pEC50
polygodial	Activation	6.4	pEC50
benzoquinone	Activation	6.4	pEC50
cannabidiol	Agonist	6.32	pEC50
isovelleral	Activation	6.3	pEC50
ASP7663	Activation	6.29	pEC50
cannabigerol	Agonist	6.15	pEC50
super cinnamaldehyde	Activation	6.1	pEC50
phytocannabinoid 6 [PMID: 38408345]	Agonist	6.0	pEC50

Binding affinities (BindingDB)

504 measured of 681 human assays (681 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-N-[2-[2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]-N-[2-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-(3,4-dichlorophenyl)-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[2-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-2-pyridinyl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-(3,4-dichlorophenyl)-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[6-(3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-1,3-thiazol-4-yl]-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[6-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-dioxo-5H-purin-7-ium-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]pyrimidin-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[6-methoxy-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[6-ethoxy-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[6-methoxy-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[6-ethoxy-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-(1-but-2-ynyl-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl)-N-[2-[2-[(2R)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
2-[3-methyl-1-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]acetamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-1,3-thiazol-4-yl]acetamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
2-[3-methyl-1-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-1,3-thiazol-4-yl]acetamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-(1-but-2-ynyl-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl)-N-[2-[6-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-(1-but-2-ynyl-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl)-N-[2-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanamide	IC50	1 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
N-[4-[3,5-dichloro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	1.45 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)acetamide	IC50	1.68 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-5H-purin-7-ium-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-2-pyridinyl]-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-2,6-dioxo-1-(2-oxopropyl)-4,5-dihydropurin-7-yl]-N-[2-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-1,3-thiazol-4-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-(3,4-dichlorophenyl)-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxopropyl)-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[2-(diethylamino)pyrimidin-5-yl]-2-pyridinyl]-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[2-(diethylamino)pyrimidin-5-yl]-1,3-thiazol-4-yl]-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[2-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[2-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-1,3-thiazol-4-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[6-(3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxopropyl)-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[6-(3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]-1,3-thiazol-4-yl]-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[6-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]-2-pyridinyl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[1-(cyanomethyl)-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[6-(6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)-3-pyridinyl]pyrazin-2-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]-N-[2-[5-methyl-6-(trifluoromethyl)-3-pyridinyl]-1,3-thiazol-4-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]pyrazin-2-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[5-(3-azabicyclo[3.1.0]hexan-3-yl)pyrazin-2-yl]-2-pyridinyl]-2-[3-methyl-2,6-dioxo-1-(2-oxobutyl)-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]pyrimidin-4-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[6-[6-chloro-5-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[6-[5-methyl-6-(trifluoromethyl)-3-pyridinyl]-2-pyridinyl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-1,3-thiazol-4-yl]-2-(1-but-2-ynyl-3-methyl-2,6-dioxo-4,5-dihydropurin-7-yl)propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-N-[2-[2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl]-1,3-thiazol-4-yl]-2-[3-methyl-2,6-dioxo-1-(2-oxopropyl)-4,5-dihydropurin-7-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]-1,3-thiazol-4-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
(2S)-2-[3-methyl-1-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-2,6-dioxo-4,5-dihydropurin-7-yl]-N-[2-[6-methyl-5-(trifluoromethyl)-3-pyridinyl]pyrimidin-4-yl]propanamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel
2-[3-methyl-2,6-dioxo-1-(pyridin-2-ylmethyl)-4,5-dihydropurin-7-yl]-N-[6-[2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]pyrimidin-5-yl]-2-pyridinyl]acetamide	IC50	2 nM	US-10221177: Inhibiting the transient receptor potential A1 ion channel

ChEMBL bioactivities

2337 potent at pChembl≥5 of 2481 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	EC50	0.05	nM	CHEMBL1084637
10.22	EC50	0.06026	nM	CHEMBL1084637
10.12	EC50	0.07586	nM	CHEMBL1084640
10.10	EC50	0.08	nM	CHEMBL1084640
10.00	EC50	0.1	nM	CHEMBL1085102
10.00	EC50	0.1	nM	CHEMBL1256241
9.96	EC50	0.11	nM	CHEMBL1084097
9.94	EC50	0.1148	nM	CHEMBL1084097
9.93	EC50	0.1175	nM	CHEMBL1084098
9.82	EC50	0.15	nM	CHEMBL1256240
9.52	IC50	0.3	nM	CHEMBL5900571
9.52	EC50	0.302	nM	DIBENZO[B,F][1,4]OXAZEPINE
9.52	EC50	0.3	nM	DIBENZO[B,F][1,4]OXAZEPINE
9.40	EC50	0.4	nM	CHEMBL1085103
9.38	IC50	0.42	nM	CHEMBL5952117
9.24	EC50	0.5754	nM	CHEMBL1085103
9.24	EC50	0.5754	nM	CHEMBL1084639
9.22	EC50	0.6	nM	CHEMBL1084639
9.19	EC50	0.65	nM	CHEMBL4516422
9.18	IC50	0.66	nM	CHEMBL5869397
9.15	IC50	0.7	nM	CHEMBL4208555
9.14	IC50	0.72	nM	CHEMBL4208555
9.14	IC50	0.73	nM	CHEMBL5952658
9.10	IC50	0.8	nM	CHEMBL6057282
9.10	IC50	0.8	nM	CHEMBL5900571
9.06	IC50	0.88	nM	CHEMBL4849329
9.05	EC50	0.9	nM	CHEMBL1256101
9.00	IC50	1	nM	CHEMBL3907685
9.00	IC50	1	nM	CHEMBL5408439
9.00	IC50	1	nM	CHEMBL5809370
9.00	IC50	1	nM	CHEMBL5951849
9.00	IC50	1	nM	CHEMBL5780817
9.00	IC50	1	nM	CHEMBL5912915
9.00	IC50	1	nM	CHEMBL6049789
9.00	IC50	1	nM	CHEMBL5794855
9.00	IC50	1	nM	CHEMBL6037240
9.00	IC50	1	nM	CHEMBL6010308
9.00	IC50	1	nM	CHEMBL5943742
9.00	IC50	1	nM	CHEMBL6051212
9.00	IC50	1	nM	CHEMBL5927515
9.00	IC50	1	nM	CHEMBL5806996
9.00	IC50	1	nM	CHEMBL6014001
9.00	IC50	1	nM	CHEMBL5772739
9.00	IC50	1	nM	CHEMBL5780751
9.00	IC50	1	nM	CHEMBL5924035
9.00	IC50	1	nM	CHEMBL5992488
9.00	IC50	1	nM	CHEMBL5989150
9.00	IC50	1	nM	CHEMBL5929322
9.00	IC50	1	nM	CHEMBL6013485
9.00	IC50	1	nM	CHEMBL6009992

PubChem BioAssay actives

632 with measured affinity, of 1904 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
benzo[b][1,4]benzoxazepine-10-carbonitrile	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0001	uM
methyl benzo[b][1,4]benzoxazepine-10-carboxylate	482136: Activation of human TRPA1 channel	ec50	0.0001	uM
methyl 11H-benzo[c][1]benzazepine-10-carboxylate	482136: Activation of human TRPA1 channel	ec50	0.0001	uM
benzo[b][1,4]benzoxazepine-10-carboxamide	482136: Activation of human TRPA1 channel	ec50	0.0001	uM
benzo[b][1,4]benzoxazepine-1-carboxamide	482136: Activation of human TRPA1 channel	ec50	0.0001	uM
methyl benzo[b][1,4]benzoxazepine-1-carboxylate	482136: Activation of human TRPA1 channel	ec50	0.0001	uM
benzo[b][1,4]benzoxazepine-1-carbonitrile	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0001	uM
benzo[b][1,4]benzoxazepine	482136: Activation of human TRPA1 channel	ec50	0.0003	uM
methyl 11H-benzo[c][1]benzazepine-2-carboxylate	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0004	uM
2-chloro-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-N-(3-methoxypropyl)acetamide	2132479: Agonist activity at TRPA1 (unknown origin)	ec50	0.0006	uM
methyl 11H-benzo[c][1]benzazepine-1-carboxylate	482136: Activation of human TRPA1 channel	ec50	0.0006	uM
2-[(2-chlorophenyl)methylidene]propanedinitrile	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0009	uM
1-(4-chlorophenyl)-N-[2-[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]-3-phenylpropyl]cyclopentane-1-carboxamide	1318854: Inhibition of cinnamaldehyde-activated full length human TRPA1 channel expressed in 293T-Rex cells monitored at 5 sec interval by manual patch clamp electrophysiological method	ic50	0.0010	uM
2-[(3,3-difluorocyclobutyl)amino]-N-(3-ethylpent-1-yn-3-yl)pyridine-3-carboxamide	1966106: Antagonist activity at human wildtype TRPA1 channel expressed in CHO-K1 cells tagged with GCaMP6 by measuring calcium flux measured after 24 hrs by FLIPR tetra analysis	ic50	0.0010	uM
1-[[3-[(3R,5R)-5-(4-chlorophenyl)oxolan-3-yl]-1,2,4-oxadiazol-5-yl]methyl]-7-methylpurin-6-one	1768806: Antagonist activity at human TRPA1 expressed in CHO cells measured by calcium based FLIPR assay	ic50	0.0012	uM
(2S,4R,5S)-4-fluoro-1-(4-fluorophenyl)sulfonyl-5-methyl-N-[[5-(trifluoromethyl)-2-[2-(trifluoromethyl)pyrimidin-5-yl]-4-pyridinyl]methyl]pyrrolidine-2-carboxamide	1768806: Antagonist activity at human TRPA1 expressed in CHO cells measured by calcium based FLIPR assay	ic50	0.0016	uM
11H-benzo[c][1]benzazepine-10-carbonitrile;hydrochloride	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0016	uM
1-(4-chlorophenyl)-N-[3-(4-fluorophenyl)-2-[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]propyl]cyclopropane-1-carboxamide	1318854: Inhibition of cinnamaldehyde-activated full length human TRPA1 channel expressed in 293T-Rex cells monitored at 5 sec interval by manual patch clamp electrophysiological method	ic50	0.0020	uM
benzo[b][1,4]benzoxazepin-9-ol	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0021	uM
11H-benzo[c][1]benzazepine-10-carboxamide	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0025	uM
1-[[3-[(1R,5S)-3-(3-chlorophenyl)-3-azabicyclo[3.1.0]hexan-6-yl]-1,2,4-oxadiazol-5-yl]methyl]-7-methylpurin-6-one	1768806: Antagonist activity at human TRPA1 expressed in CHO cells measured by calcium based FLIPR assay	ic50	0.0029	uM
11H-benzo[c][1]benzazepine	482136: Activation of human TRPA1 channel	ec50	0.0030	uM
10-bromo-11H-benzo[c][1]benzazepine;hydrochloride	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0035	uM
1-(4-fluorophenyl)-N-[2-[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]-3-phenylpropyl]cyclohexane-1-carboxamide	1318854: Inhibition of cinnamaldehyde-activated full length human TRPA1 channel expressed in 293T-Rex cells monitored at 5 sec interval by manual patch clamp electrophysiological method	ic50	0.0040	uM
trans-(1S,2R)-2-[(4-fluorophenyl)methyl]-1-(trifluoromethyl)cyclohexan-1-ol	1966103: Antagonist activity at human TRPA1 channel expressed in CHO-K1 cells tagged with GCaMP6 by measuring calcium flux measured after 10 mins by FLIPR tetra analysis	ic50	0.0040	uM
(2S,4R,5S)-N-[[2-cyclopropyl-6-[2-(trifluoromethyl)pyrimidin-5-yl]pyrimidin-4-yl]methyl]-4-fluoro-1-(4-fluorophenyl)sulfonyl-5-methylpyrrolidine-2-carboxamide	1479996: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of cinnamaldehyde-induced Ca2+ influx preincubated for 20 mins followed by cinnamaldehyde induction by FLIPR assay	ic50	0.0050	uM
(2S,4R,5S)-N-[[5-chloro-2-[2-(trifluoromethyl)pyrimidin-5-yl]-4-pyridinyl]methyl]-4-fluoro-1-(4-fluorophenyl)sulfonyl-5-methylpyrrolidine-2-carboxamide	1479996: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of cinnamaldehyde-induced Ca2+ influx preincubated for 20 mins followed by cinnamaldehyde induction by FLIPR assay	ic50	0.0050	uM
trans-(1R,2S)-2-[(5-chlorothiophen-3-yl)methyl]-1-(trifluoromethyl)cyclohexan-1-ol	1966103: Antagonist activity at human TRPA1 channel expressed in CHO-K1 cells tagged with GCaMP6 by measuring calcium flux measured after 10 mins by FLIPR tetra analysis	ic50	0.0050	uM
methyl benzo[b][1,4]benzoxazepine-9-carboxylate	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0060	uM
(2S,4R,5S)-N-[[5-cyano-2-[2-(trifluoromethyl)pyrimidin-5-yl]-4-pyridinyl]methyl]-4-fluoro-1-(4-fluorophenyl)sulfanyl-5-methylpyrrolidine-2-carboxamide	1966106: Antagonist activity at human wildtype TRPA1 channel expressed in CHO-K1 cells tagged with GCaMP6 by measuring calcium flux measured after 24 hrs by FLIPR tetra analysis	ic50	0.0061	uM
butyl 11H-benzo[c][1]benzazepine-10-carboxylate;hydrochloride	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0062	uM
1-(4-chlorophenyl)-N-[3-phenyl-2-[4-(trifluoromethyl)piperidin-1-yl]propyl]cyclopentane-1-carboxamide	1318854: Inhibition of cinnamaldehyde-activated full length human TRPA1 channel expressed in 293T-Rex cells monitored at 5 sec interval by manual patch clamp electrophysiological method	ic50	0.0070	uM
N-[2,2,2-trichloro-1-(4-chlorophenyl)sulfanylethyl]benzamide	482158: Antagonist activity at human TRPA1 channel assessed as inhibition of noxious cold-induced receptor activation	ic50	0.0070	uM
3-[3-(4-chlorophenyl)cyclobutyl]-5-[(7-methyl-6-oxopurin-1-yl)methyl]-1,3,4-oxadiazol-2-one	1768806: Antagonist activity at human TRPA1 expressed in CHO cells measured by calcium based FLIPR assay	ic50	0.0074	uM
N-(3-methoxypropyl)-11H-benzo[c][1]benzazepine-10-carboxamide;hydrochloride	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0077	uM
(2S,4R,5S)-4-fluoro-1-(4-fluorophenyl)sulfonyl-N-[[5-fluoro-2-[2-(trifluoromethyl)pyrimidin-5-yl]-4-pyridinyl]methyl]-5-methylpyrrolidine-2-carboxamide	1479996: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of cinnamaldehyde-induced Ca2+ influx preincubated for 20 mins followed by cinnamaldehyde induction by FLIPR assay	ic50	0.0080	uM
butyl 11H-benzo[c][1]benzazepine-10-carboxylate	482136: Activation of human TRPA1 channel	ec50	0.0085	uM
4-[[3-[(2S)-2-(4-chlorophenyl)-2-hydroxyethyl]-1,2,4-oxadiazol-5-yl]methyl]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-triene-3,10-dione	1777603: Antagonist activity against human TRPA1 expressed in HEK293K cells assessed as inhibition of AITC-induced intracellular calcium accumulation measured after 120 mins by FLIPR assay	ic50	0.0090	uM
3-[[2-[(2S)-2-(6-fluoro-1-benzothiophen-2-yl)-2-hydroxyethyl]tetrazol-5-yl]methyl]-4-oxothieno[2,3-d]pyrimidine-5-carboxamide	1870717: Inhibition of human TRPA1 overexpressed in human HEK293 cells assessed as reduction in AITC-induced calcium influx incubated for 10 mins by FLIPR assay	ic50	0.0090	uM
benzo[b][1,4]benzothiazepine	516893: Agonist activity at human TRPA1 expressed in T-REx-HEK293 cells assessed as increase of intracellular calcium level by FDSS assay	ec50	0.0090	uM
(2S,4R,5S)-N-[[5-cyano-2-[2-(trifluoromethyl)pyrimidin-5-yl]-4-pyridinyl]methyl]-4-fluoro-1-(4-fluorophenyl)sulfonyl-5-methylpyrrolidine-2-carboxamide	1479996: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of cinnamaldehyde-induced Ca2+ influx preincubated for 20 mins followed by cinnamaldehyde induction by FLIPR assay	ic50	0.0100	uM
3-[[3-[(2S)-2-(4-chlorophenyl)-2-hydroxyethyl]-1,2,4-oxadiazol-5-yl]methyl]-N,5-dimethyl-4-oxothieno[2,3-d]pyrimidine-6-carboxamide	1777603: Antagonist activity against human TRPA1 expressed in HEK293K cells assessed as inhibition of AITC-induced intracellular calcium accumulation measured after 120 mins by FLIPR assay	ic50	0.0100	uM
3-[[2-[(2S)-2-(6-fluoro-1-benzothiophen-2-yl)-2-hydroxyethyl]tetrazol-5-yl]methyl]-6-methyl-4-oxofuro[2,3-d]pyrimidine-5-carboxamide	1886980: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of AITC-induced intracellular calcium accumulation incubated for 10 mins by FLIPR-tetra assay	ic50	0.0100	uM
3-[[2-[(2S)-2-(1-benzothiophen-2-yl)-2-hydroxyethyl]tetrazol-5-yl]methyl]-5-methyl-4-oxofuro[2,3-d]pyrimidine-6-carboxamide	1886980: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of AITC-induced intracellular calcium accumulation incubated for 10 mins by FLIPR-tetra assay	ic50	0.0100	uM
3-[[2-[(2S)-2-(5-chlorothiophen-2-yl)-2-hydroxyethyl]tetrazol-5-yl]methyl]-5-methyl-4-oxofuro[2,3-d]pyrimidine-6-carboxamide	1886980: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of AITC-induced intracellular calcium accumulation incubated for 10 mins by FLIPR-tetra assay	ic50	0.0100	uM
2-bromo-2-phenylacetonitrile	482136: Activation of human TRPA1 channel	ec50	0.0100	uM
(4R)-4-(3-methoxyphenyl)-2-sulfanylidene-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5-one	640978: Antagonist activity at human TRPA1 expressed in HEK293 cells assessed as inhibition of N-methyl-maleimide-induced current by patch clamp assay	ec50	0.0100	uM
5-chloro-N-[3-methyl-1-(4-nitrophenyl)-1-oxobutan-2-yl]-2-(trifluoromethyl)benzamide	678130: Antagonist activity at human TRPA1 expressed in HEK293 cells assessed as inhibition of Zn2+-induced intracellular calcium flux by FLIPR assay	ic50	0.0100	uM
3-[[2-[(2S)-2-(1-benzothiophen-2-yl)-2-hydroxyethyl]tetrazol-5-yl]methyl]-6-methyl-4-oxofuro[2,3-d]pyrimidine-5-carboxamide	1886980: Inhibition of human TRPA1 expressed in HEK293 cells assessed as inhibition of AITC-induced intracellular calcium accumulation incubated for 10 mins by FLIPR-tetra assay	ic50	0.0110	uM
N-[3-(4-bromophenyl)-2-[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]propyl]-1-(4-chlorophenyl)cyclopentane-1-carboxamide	1318854: Inhibition of cinnamaldehyde-activated full length human TRPA1 channel expressed in 293T-Rex cells monitored at 5 sec interval by manual patch clamp electrophysiological method	ic50	0.0120	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
allyl isothiocyanate	affects response to substance, decreases reaction, increases uptake, affects cotreatment, affects reaction (+4 more)	10
Calcium	increases activity, decreases reaction, increases transport, increases import, increases reaction (+3 more)	7
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
cinnamaldehyde	decreases reaction, increases reaction, affects reaction, affects response to substance, increases response to substance (+4 more)	6
2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide	decreases reaction, increases activity, decreases activity	4
Vehicle Emissions	increases activity, affects binding, increases import	4
Smoke	decreases reaction, increases expression, increases activity, increases response to substance	4
2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate	increases activity, increases response to substance	3
Mustard Gas	increases response to substance, decreases reaction, increases activity, increases uptake, increases alkylation	3
Coal Ash	affects activity, affects binding, increases activity, affects response to substance	3
4-(4-chlorophenyl)-3-methylbut-3-en-2-oxime	decreases reaction, increases activity, increases uptake	2
2-chloroethyl ethyl sulfide	increases activity, increases uptake, decreases reaction, increases response to substance	2
hydroquinone	increases reaction, decreases reaction, increases activity, increases import	2
phenalen-1-one	decreases reaction, increases activity	2
2,4-di-tert-butylphenol	increases activity	2
cannabidivarin	increases expression, increases reaction, increases activity, increases uptake	2
Acrolein	increases uptake, affects response to substance, increases activity, affects reaction, increases secretion	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cannabidiol	increases activity, increases expression	2
Glutathione	increases activity, decreases reaction	2
Ruthenium Red	affects cotreatment, increases phosphorylation, decreases activity, decreases reaction, increases activity	2
Aflatoxin B1	increases expression	2
Particulate Matter	decreases reaction, increases activity	2
3,5-di-tert-butylphenol	increases activity	1
tetrahydrocannabivarin 9	increases activity, increases expression, increases reaction	1
lasiocarpine	increases expression	1
tributyrin	increases activity	1
cannabidiolic acid	increases activity	1
2,2’,2’’-trichlorotriethylamine	increases activity, increases response to substance	1
cannabichromene	increases activity	1

ChEMBL screening assays

344 unique, capped per target: 289 binding, 49 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1049519	Functional	Agonist activity at human TRPA1 expressed in HEK293 cells assessed as [45]Ca2+ influx by microbeta plate count	Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor. — Bioorg Med Chem Lett
CHEMBL1118236	Binding	Activation of human TRPA1 channel	Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. — J Med Chem
CHEMBL4022610	ADMET	Agonist activity at human TRPA1 expressed in HEK293 cells assessed as induction of calcium influx at 30 uM after 6 mins by Fluo-4 dye-based assay	Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 3 induced pluripotent stem cell, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D0NB	UKWNLi008-A	Induced pluripotent stem cell	Male
CVCL_D0NC	UKWNLi008-B	Induced pluripotent stem cell	Male
CVCL_D0ND	UKWNLi008-C	Induced pluripotent stem cell	Male
CVCL_D1KL	PrecisION hTRPA1-HEK	Transformed cell line	Female
CVCL_D6A5	HyCyte HEK293T KO-hTRPA1	Transformed cell line	Female
CVCL_E5JD	HEK293/TRPA1	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03278093	Not specified	UNKNOWN	Effect of Orthoses and Underfoot Vibration on Balance in Neuropathy