TRPV1

Summary

TRPV1 (transient receptor potential cation channel subfamily V member 1, HGNC:12716) is a protein-coding gene on chromosome 17p13.2, encoding Transient receptor potential cation channel subfamily V member 1 (Q8NER1). Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli.

Capsaicin, the main pungent ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The protein encoded by this gene is a receptor for capsaicin and is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. This receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo. Four transcript variants encoding the same protein, but with different 5’ UTR sequence, have been described for this gene.

Source: NCBI Gene 7442 — RefSeq curated summary.

At a glance

• Gene–disease (curated): malignant hyperthermia, susceptibility to (Moderate, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 185 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_080704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12716
Approved symbol	TRPV1
Name	transient receptor potential cation channel subfamily V member 1
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196689
Ensembl biotype	protein_coding
OMIM	602076
Entrez	7442

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000310522, ENST00000399756, ENST00000399759, ENST00000425167, ENST00000570742, ENST00000571088, ENST00000572705, ENST00000574085, ENST00000576351, ENST00000650505, ENST00000891172, ENST00000966581

RefSeq mRNA: 4 — MANE Select: NM_080704 NM_018727, NM_080704, NM_080705, NM_080706

CCDS: CCDS45576

Canonical transcript exons

ENST00000572705 — 17 exons

Exon	Start	End
ENSE00002650748	3609309	3609411
ENSE00002681298	3608427	3608565
ENSE00003784156	3585768	3585926
ENSE00003784744	3572122	3572249
ENSE00003785270	3580457	3580527
ENSE00003785418	3589807	3590105
ENSE00003786808	3588188	3588367
ENSE00003786814	3583338	3583430
ENSE00003787052	3592067	3592383
ENSE00003787559	3590252	3590392
ENSE00003788539	3571524	3571639
ENSE00003789222	3591187	3591353
ENSE00003789676	3590964	3591116
ENSE00003789927	3577126	3577192
ENSE00003791367	3573633	3573955
ENSE00003791522	3577598	3577763
ENSE00003918508	3565446	3566987

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 85.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1021 / max 54.2742, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163853	0.1021	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	85.74	gold quality
sural nerve	UBERON:0015488	84.22	gold quality
tibial nerve	UBERON:0001323	82.81	gold quality
apex of heart	UBERON:0002098	82.26	gold quality
cerebellar hemisphere	UBERON:0002245	80.74	gold quality
cerebellar cortex	UBERON:0002129	80.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.47	gold quality
right uterine tube	UBERON:0001302	80.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.12	gold quality
left ovary	UBERON:0002119	79.84	gold quality
metanephros cortex	UBERON:0010533	79.78	gold quality
right ovary	UBERON:0002118	79.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.13	gold quality
endocervix	UBERON:0000458	78.76	gold quality
cerebellum	UBERON:0002037	78.75	gold quality
gastrocnemius	UBERON:0001388	78.02	gold quality
mucosa of transverse colon	UBERON:0004991	77.72	gold quality
tibial artery	UBERON:0007610	77.63	gold quality
ovary	UBERON:0000992	77.62	gold quality
popliteal artery	UBERON:0002250	77.62	gold quality
cortical plate	UBERON:0005343	77.46	gold quality
mucosa of stomach	UBERON:0001199	77.43	gold quality
ectocervix	UBERON:0012249	77.32	gold quality
small intestine	UBERON:0002108	77.31	gold quality
muscle of leg	UBERON:0001383	77.27	gold quality
right atrium auricular region	UBERON:0006631	77.24	gold quality
ventricular zone	UBERON:0003053	77.14	gold quality
vagina	UBERON:0000996	76.95	gold quality
inferior olivary complex	UBERON:0002127	76.95	silver quality
body of pancreas	UBERON:0001150	76.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PPARGC1A	Repression

Upstream regulators (CollecTRI, top): CEBPB, HSF1, IRF6, RUNX1, SP1, SP4

miRNA regulators (miRDB)

61 targeting TRPV1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-587	99.64	70.86	2611

Literature-anchored findings (GeneRIF, showing 40)

• Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues (PMID:11884385)
• ASICs are leading acid sensors in human nociceptors and VR1 participates in the nociception mainly under extremely acidic conditions. (PMID:12393854)
• In rectal hypersensitivity, nerve fibres immunoreactive to TRPV1 were increased in muscle, submucosal, and mucosal layers. (PMID:12573376)
• calmodulin binds to a 35-aa segment in the C terminus of TRPV1, and disruption of the calmodulin-binding segment prevents TRPV1 desensitization (PMID:12808128)
• Proposal that residue Y671 is critical for the high relative Ca(2+) permeability of TRPV1 and participates in the structural rearrangements of the channel protein leading to Ca(2+)-dependent desensitization. (PMID:12812762)
• Ser-116 and possibly Thr-370 are the most important residues involved in the cyclic AMP-dependent protein kinase pathway reduction of desensitization of capsaicin-activated currents. (PMID:14506258)
• Ser-116 and possibly Thr-370 of vanilloid receptor TRPV1 are the most important residues involved in the mechanism of PKA-dependent reduction of desensitization of capsaicin-activated currents (PMID:14506258)
• in fibers of human tooth pulp … may play a role in perception of dental pain (PMID:14520770)
• vanilloid receptor 1 has a role in regulating vanilloid binding with Ca2+/calmodulin-dependent kinase II (PMID:14630912)
• VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation. (PMID:14987252)
• Review notes that high expression of TRPV1 has been detected in inflammatory diseases of the colon and ileum, whereas neuropeptides released upon sensory nerve stimulation triggered by TRPV1 activation may play a role in intestinal motility disorders. (PMID:15051629)
• Our observations suggest that the homologous TRP domain in the TRP protein family may function as a general, evolutionary conserved AD involved in subunit multimerization (PMID:15190102)
• temperature sensing is tightly linked to voltage-dependent gating in the cold-sensitive channel TRPM8 and the heat-sensitive channel TRPV1 (PMID:15306801)
• There is a minor role for transient receptor potential vanilloid receptor-1 as a mediator of cutaneous acid-induced pain. (PMID:15574747)
• TRPV1b receptors are expressed in trigeminal ganglion neurons and contribute to thermal nociception. (PMID:15644492)
• Piperine was agonistic to TRPV1 as measured by patch-clamp techniques. TRPV1 was antagonized by the competitive antagonist capsazepine and the non-competitive TRPV1 blocker ruthenium red. (PMID:15685214)
• Ca2+-dependent desensitization of TRPV1 might be in part regulated through channel dephosphorylation by calcineurin (PMID:15691846)
• Increased urothelial TRPV1 in patients with neurogenic detrusor overactivity may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. (PMID:15708075)
• expression of vanilloid receptor subtype-1 and acid-sensing ion channel genes in the human trigeminal ganglion neurons (PMID:15738111)
• TRPV1 as a significant novel player in human hair growth control. (PMID:15793280)
• A progressive loss of TRPV1 expression in the urothelium as TCC stage increased and cell differentiation was lower. (PMID:15992990)
• several endogenous non-cannabinoid N-acylethanolamines activate TRPV(1) (PMID:16081411)
• Gadolinium activates and potentiates the TRPV1 by neutralizing two specific proton-sensitive sites on the extracellular side of the pore-forming loop. (PMID:16099171)
• may play a role in maintenance of the physiologic condition of the TMJ (PMID:16301147)
• NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels (PMID:16319926)
• Results describe the modification of 12-phenylacetyl-ricinoleoyl-vanillamide and its activity at TRPV1 and CB2 receptors. (PMID:16406364)
• Both TRPV1 and TRPV2 are found in human peripheral blood lymphocytes. (PMID:16777226)
• PAR2 activates PKCepsilon and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia (PMID:16793902)
• Opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit protein kinase A-potentiated TRPV1 responses. (PMID:16842630)
• TRPV1 antagonists, including TRPV1 siRNAs, have potential in the treatment of both, neuropathic and visceral pain (PMID:16996476)
• Here, we review the potential therapeutic indications and adverse effects of TRPV1 antagonists. (PMID:16996800)
• TRPV1 may play a role in urinary sensory urgency and premature first bladder sensation on filling. (PMID:17016800)
• data support the hypothesis that the TRPV1b splice variant is a naturally existing inhibitory modulator of TRPV1. (PMID:17018028)
• We propose a new model for nerve growth factor (NGF)-mediated hyperalgesia in which physical coupling of TRPV1 and PI3K in a signal transduction complex facilitates trafficking of TRPV1 to the plasma membrane. (PMID:17074976)
• These data do not rule out involvement of TRPV1 in the aetiology of burning dysaesthesia following lingual nerve injury but suggest that TRPV1 at the injury site does not play a primary role. (PMID:17109831)
• Gingerols and shogaols activated TRPV1 and increased adrenaline secretion. (PMID:17176640)
• we assigned a novel role to capsaicin-sensitive TRPV1 channels. They are important Ca2+ influx channels required for cell migration. (PMID:17184838)
• TRPV1 is a nonselective cation channel with significant permeability to calcium, protons, and large polyvalent cations–{REVIEW} (PMID:17217056)
• Capsaicin-induced calcium influx through TRPV1 channels prevents adipogenesis, prevents downregulation of TRPV1 expression and prevents obesity. (PMID:17347480)
• IGF-I and insulin enhance TRPV1 protein expression and activity, and impaired pain sensation might result from distorted TRPV1 regulation in the peripheral nervous system (PMID:17385724)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trpv1	ENSMUSG00000005952
rattus_norvegicus	Trpv1	ENSRNOG00000019486
drosophila_melanogaster		FBGN0036414
drosophila_melanogaster	iav	FBGN0086693
caenorhabditis_elegans		WBGENE00003841
caenorhabditis_elegans		WBGENE00003889

Paralogs (5): TRPV4 (ENSG00000111199), TRPV5 (ENSG00000127412), TRPV6 (ENSG00000165125), TRPV3 (ENSG00000167723), TRPV2 (ENSG00000187688)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily V member 1 — Q8NER1 (reviewed: Q8NER1)

Alternative names: Capsaicin receptor, Osm-9-like TRP channel 1, Vanilloid receptor 1

All UniProt accessions (5): A0A3B3ISI9, E7EQ78, E7ESJ2, Q8NER1, I3L1R6

UniProt curated annotations — full annotation on UniProt →

Function. Non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activated by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius. Upon activation, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.

Subunit / interactions. Homotetramer. Interacts with PIRT. Interacts with TRPV3 and may also form a heteromeric channel with TRPV3. Interacts with CALM, PRKCM and CSK. Interacts with PRKCG and NTRK1, probably by forming a trimeric complex. Interacts with the Scolopendra mutilans RhTx toxin. Interacts with TMEM100. Interacts with PACS2.

Subcellular location. Postsynaptic cell membrane. Cell projection. Dendritic spine membrane. Cell membrane.

Tissue specificity. Widely expressed at low levels. Expression is elevated in dorsal root ganglia. In skin, expressed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands (at protein level).

Post-translational modifications. Phosphorylation by PKA reverses capsaicin-induced dephosphorylation at multiple sites, probably including Ser-117 as a major phosphorylation site. Phosphorylation by CAMKII seems to regulate binding to vanilloids. Phosphorylated and modulated by PRKCE, PRKCM and probably PRKCZ. Dephosphorylation by calcineurin seems to lead to receptor desensitization and phosphorylation by CAMKII recovers activity.

Activity regulation. Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity. The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. Intracellular PIP2 inhibits desensitization. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation. The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state).

Domain organisation. The association domain (AD) is necessary for self-association.

Miscellaneous. Responses evoked by low pH and heat, and capsaicin can be antagonized by capsazepine.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV1 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NER1-1	1	yes
Q8NER1-3	2

RefSeq proteins (4): NP_061197, NP_542435, NP_542436, NP_542437 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR005821	Ion_trans_dom	Domain
IPR008347	TrpV1-4	Family
IPR024862	TRPV	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF00520, PF12796

Catalyzed reactions (Rhea), 4 shown:

• 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 (112 total): helix 31, strand 14, binding site 12, topological domain 8, modified residue 8, repeat 7, transmembrane region 6, mutagenesis site 6, sequence variant 5, turn 4, region of interest 4, sequence conflict 2, chain 1, intramembrane region 1, short sequence motif 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
11CL	ELECTRON MICROSCOPY	2.1
8GFA	ELECTRON MICROSCOPY	2.29
11CN	ELECTRON MICROSCOPY	2.37
11CO	ELECTRON MICROSCOPY	2.49
11CJ	ELECTRON MICROSCOPY	2.52
8X94	ELECTRON MICROSCOPY	2.55
8GF9	ELECTRON MICROSCOPY	2.58
9P6B	ELECTRON MICROSCOPY	2.74
8JQR	ELECTRON MICROSCOPY	2.75
8YCP	ELECTRON MICROSCOPY	2.87
8GF8	ELECTRON MICROSCOPY	2.9
11CK	ELECTRON MICROSCOPY	2.9
6L93	X-RAY DIFFRACTION	4.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NER1-F1	72.49	0.27

Functional residue map

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

Ligand- & substrate-binding residues (12): 116; 156; 161; 165; 200–203; 211–212; 511–512; 550; 557; 644; 644; 647

Post-translational modifications (8): 117, 145, 371, 502, 705, 775, 801, 821

Glycosylation sites (1): 604

Mutagenesis-validated functional residues (6):

Position	Phenotype
511	loss of sensitivity to capsaicin. impairs response to inhibitor sb-366791.
515	abolishes response to inhibitor sb-366791.
547	abolishes response to inhibitor sb-366791.
550	abolishes response to inhibitor sb-366791.
550	reduces sensitivity to capsaicin 40-fold.
693	abolishes response to inhibitor sb-366791.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 0 (showing top):

GO Biological Process (36): negative regulation of transcription by RNA polymerase II (GO:0000122), fever generation (GO:0001660), diet induced thermogenesis (GO:0002024), peptide secretion (GO:0002790), lipid metabolic process (GO:0006629), cell surface receptor signaling pathway (GO:0007166), chemosensory behavior (GO:0007635), cellular response to heat (GO:0034605), behavioral response to pain (GO:0048266), sensory perception of taste (GO:0050909), sensory perception of mechanical stimulus (GO:0050954), thermoception (GO:0050955), detection of temperature stimulus involved in thermoception (GO:0050960), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), detection of chemical stimulus involved in sensory perception of pain (GO:0050968), protein homotetramerization (GO:0051289), smooth muscle contraction involved in micturition (GO:0060083), calcium ion transmembrane transport (GO:0070588), cellular response to alkaloid (GO:0071312), cellular response to ATP (GO:0071318), cellular response to acidic pH (GO:0071468), calcium ion import across plasma membrane (GO:0098703), response to capsazepine (GO:1901594), temperature homeostasis (GO:0001659), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), response to pH (GO:0009268), response to heat (GO:0009408), urinary bladder smooth muscle contraction (GO:0014832), sensory perception of pain (GO:0019233), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), response to pain (GO:0048265), transmembrane transport (GO:0055085), excitatory postsynaptic potential (GO:0060079), calcium ion import into cytosol (GO:1902656)

GO Molecular Function (15): transmembrane signaling receptor activity (GO:0004888), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), excitatory extracellular ligand-gated monoatomic ion channel activity (GO:0005231), voltage-gated calcium channel activity (GO:0005245), calcium channel activity (GO:0005262), calmodulin binding (GO:0005516), ATP binding (GO:0005524), intracellularly gated calcium channel activity (GO:0015278), phosphatidylinositol binding (GO:0035091), metal ion binding (GO:0046872), phosphoprotein binding (GO:0051219), temperature-gated ion channel activity (GO:0097603), nucleotide binding (GO:0000166), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), membrane (GO:0016020), dendritic spine membrane (GO:0032591), postsynaptic membrane (GO:0045211), GABA-ergic synapse (GO:0098982), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202)

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
behavior	2
detection of temperature stimulus involved in sensory perception	2
sensory perception of pain	2
cellular response to nitrogen compound	2
protein binding	2
cellular anatomical structure	2
synaptic membrane	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
acute-phase response	1
heat generation	1
response to dietary excess	1
adaptive thermogenesis	1
peptide transport	1
secretion	1
primary metabolic process	1
signal transduction	1
response to chemical	1
response to heat	1
cellular response to stress	1
response to pain	1
sensory perception of chemical stimulus	1
sensory perception	1
sensory perception of temperature stimulus	1
thermoception	1
detection of chemical stimulus involved in sensory perception	1
protein homooligomerization	1
protein tetramerization	1
urinary bladder smooth muscle contraction	1
micturition	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
response to alkaloid	1
response to ATP	1
cellular response to oxygen-containing compound	1
signaling receptor activity	1
ligand-gated monoatomic ion channel activity	1
extracellular ligand-gated monoatomic ion channel activity	1
excitatory postsynaptic potential	1

Protein interactions and networks

STRING

2238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPV1	TRPM8	Q7Z2W7	995
TRPV1	TRPA1	O75762	992
TRPV1	CALML6	Q8TD86	990
TRPV1	CALML3	P27482	990
TRPV1	CALML5	Q9NZT1	990
TRPV1	CALML4	Q96GE6	990
TRPV1	CALM1	P02593	977
TRPV1	TAC1	P20366	939
TRPV1	GPR55	Q9Y2T6	922
TRPV1	KNG1	P01042	918
TRPV1	ANK1	P16157	902
TRPV1	P2RX3	P56373	897
TRPV1	TRPC1	P48995	893
TRPV1	FAAH	O00519	854
TRPV1	NGF	P01138	853

IntAct

0 interactions, top by confidence:

BioGRID (20): AKAP5 (Affinity Capture-Western), TRPV1 (Affinity Capture-Western), TRPV1 (Reconstituted Complex), AKAP5 (Reconstituted Complex), SYT9 (Two-hybrid), SNAPIN (Two-hybrid), SYT9 (Reconstituted Complex), SNAPIN (Reconstituted Complex), SYT9 (Affinity Capture-Western), SNAPIN (Affinity Capture-Western), CALM1 (Affinity Capture-Western), CALM1 (Reconstituted Complex), TRPV1 (Affinity Capture-Western), TRPV1 (Affinity Capture-RNA), OS9 (Affinity Capture-Western)

ESM2 similar proteins: A0A1D5PXA5, O18784, O35119, O35433, O62852, P0C550, P19334, P34586, P34641, P48994, P48995, P69744, P79100, P97414, Q0JKV1, Q12324, Q5ICL9, Q61056, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q875M2, Q8GXE6, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q96L42, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9MYV9, Q9NQA5, Q9P2G1, Q9QUQ5, Q9QX01, Q9QX29

Diamond homologs: A0A1D5PXA5, O35433, P69744, Q697L1, Q6R5A3, Q6RX08, Q704Y3, Q8K424, Q8NER1, Q8NET8, Q91WD2, Q9EPK8, Q9ERZ8, Q9H1D0, Q9HBA0, Q9JIP0, Q9NQA5, Q9R186, Q9WTR1, Q9WUD2, Q9XSM3, Q9Y5S1, Q810B6, Q9P2R3, P83757, Q03017

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
SB-705498	down-regulates	TRPV1	“chemical inhibition”
PRKCE	“up-regulates activity”	TRPV1	phosphorylation
PRKCB	“up-regulates activity”	TRPV1	phosphorylation
TRPV1	“up-regulates activity”	PRKCB	binding
CDK5	“up-regulates activity”	TRPV1	phosphorylation
PTPN6	“down-regulates activity”	TRPV1	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	134
Likely benign	16
Benign	6

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1069678	NC_000017.10:g.(?3392519)(3564038_?)del	Pathogenic
1301850	NM_080704.4(TRPV1):c.993C>G (p.Asn331Lys)	Likely pathogenic

SpliceAI

3322 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3571523:CCT:C	donor_gain	1.0000
17:3571635:CCACC:C	acceptor_gain	1.0000
17:3571636:CACCC:C	acceptor_gain	1.0000
17:3571638:CCCTG:C	acceptor_loss	1.0000
17:3571640:C:CA	acceptor_loss	1.0000
17:3571640:C:CC	acceptor_gain	1.0000
17:3572116:CATTA:C	donor_loss	1.0000
17:3572117:ATTAC:A	donor_loss	1.0000
17:3572118:TTACC:T	donor_loss	1.0000
17:3572119:TA:T	donor_loss	1.0000
17:3572120:ACCTG:A	donor_loss	1.0000
17:3572121:CCT:C	donor_loss	1.0000
17:3572245:GCTCT:G	acceptor_gain	1.0000
17:3572246:CTCT:C	acceptor_gain	1.0000
17:3572246:CTCTC:C	acceptor_gain	1.0000
17:3572247:TCT:T	acceptor_gain	1.0000
17:3572247:TCTCT:T	acceptor_gain	1.0000
17:3572248:CT:C	acceptor_gain	1.0000
17:3572248:CTC:C	acceptor_gain	1.0000
17:3572249:TCT:T	acceptor_gain	1.0000
17:3572250:C:CC	acceptor_gain	1.0000
17:3572250:CTG:C	acceptor_loss	1.0000
17:3572251:T:A	acceptor_loss	1.0000
17:3572254:A:T	acceptor_gain	1.0000
17:3573632:C:T	donor_loss	1.0000
17:3573641:T:TA	donor_gain	1.0000
17:3573658:T:A	donor_gain	1.0000
17:3573953:CCG:C	acceptor_gain	1.0000
17:3573954:CGC:C	acceptor_gain	1.0000
17:3577593:CCCA:C	donor_loss	1.0000

AlphaMissense

5518 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3571614:A:G	W753R	1.000
17:3571614:A:T	W753R	1.000
17:3573687:C:A	M683I	1.000
17:3573687:C:G	M683I	1.000
17:3573687:C:T	M683I	1.000
17:3573691:A:G	L682P	1.000
17:3573700:A:G	L679P	1.000
17:3573705:G:C	N677K	1.000
17:3573705:G:T	N677K	1.000
17:3573715:A:G	L674P	1.000
17:3577137:C:T	G590E	1.000
17:3577166:G:C	F580L	1.000
17:3577166:G:T	F580L	1.000
17:3577168:A:G	F580L	1.000
17:3577624:C:G	G563R	1.000
17:3577666:A:G	W549R	1.000
17:3577666:A:T	W549R	1.000
17:3585870:C:A	W427C	1.000
17:3585870:C:G	W427C	1.000
17:3585886:A:G	L422P	1.000
17:3585898:G:T	P418Q	1.000
17:3588285:C:T	G376E	1.000
17:3588286:C:G	G376R	1.000
17:3588286:C:T	G376R	1.000
17:3588295:A:G	W373R	1.000
17:3588295:A:T	W373R	1.000
17:3571612:C:A	W753C	0.999
17:3571612:C:G	W753C	0.999
17:3571621:C:A	W750C	0.999
17:3571621:C:G	W750C	0.999

dbSNP variants (sampled 300 via entrez): RS1000097754 (17:3591709 G>A), RS1000337756 (17:3566381 C>A), RS1000376978 (17:3573541 A>C,G), RS1000480863 (17:3595298 C>T), RS1000511393 (17:3595136 C>T), RS1000511890 (17:3601144 C>G), RS1000565973 (17:3571158 G>A), RS1000636566 (17:3600391 C>T), RS1000687235 (17:3590640 C>G,T), RS1000737198 (17:3600202 T>C), RS1000738841 (17:3581998 G>A,T), RS1000791426 (17:3592639 C>T), RS1000950184 (17:3572940 G>A), RS1001115023 (17:3602161 C>G), RS1001161785 (17:3590401 G>A)

Disease associations

OMIM: gene MIM:602076 | disease phenotypes: MIM:219750, MIM:219900, MIM:271900

GenCC curated gene-disease

Disease	Classification	Inheritance
malignant hyperthermia, susceptibility to	Moderate	Autosomal dominant
channelopathy-associated congenital insensitivity to pain, autosomal recessive	Limited	Autosomal recessive

Mondo (6): ocular cystinosis (MONDO:0009064), juvenile nephropathic cystinosis (MONDO:0009066), Canavan disease (MONDO:0010079), malignant hyperthermia of anesthesia (MONDO:0018493), channelopathy-associated congenital insensitivity to pain, autosomal recessive (MONDO:0009459), malignant hyperthermia, susceptibility to (MONDO:0800188)

Orphanet (5): Canavan disease (Orphanet:141), Cystinosis (Orphanet:213), Juvenile nephropathic cystinosis (Orphanet:411634), Ocular cystinosis (Orphanet:411641), Malignant hyperthermia of anesthesia (Orphanet:423)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002047	Malignant hyperthermia

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D017825	Canavan Disease	C10.228.140.163.100.362.375; C10.228.140.695.625.375; C10.314.400.375; C10.574.500.300; C16.320.400.150; C16.320.565.189.362.375; C18.452.132.100.362.375; C18.452.648.189.362.375
D008305	Malignant Hyperthermia	C23.550.505.700; C23.550.767.600; C23.888.119.455.500
C562683	Cystinosis, Late-Onset Juvenile or Adolescent Nephropathic Type (supp.)
C535765	Cystinosis, ocular nonnephropathic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4794 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 381,930 (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
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL294199	CAPSAICIN	4	52,939
CHEMBL526	PROPOFOL	4	28,835
CHEMBL17976	RESINIFERATOXIN	3	428
CHEMBL184618	FRAMYCETIN	3	217,461
CHEMBL313971	ZUCAPSAICIN	3	2,469
CHEMBL74415	CANNABINOL	3	18,794
CHEMBL118478	ILEPCIMIDE	2	207
CHEMBL207433	SB-705498	2	127
CHEMBL214796	NGD-8243	2	44
CHEMBL2364618	MAVATREP	2	46
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884
CHEMBL2387742	CANNABIDIVARIN	2	4,963
CHEMBL43185	PIPERINE	2	10,980
CHEMBL497318	CANNABIGEROL	2	11,097
CHEMBL5314399	JTS-653	2	9
CHEMBL76903	OLVANIL	2	1,800
CHEMBL229430	AMG-517	1	347
CHEMBL398338	ABT-102	1	121

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs222749	Efficacy	3	botulinum toxin type a	Migraine disorder
rs224534	Efficacy	3	acetaminophen	Pain

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs224534	TRPV1	3	1.75	1	acetaminophen
rs222749	TRPV1	3	2.50	1	botulinum toxin type a
rs222747	TRPV1		0.00	0
rs222741	TRPV1		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 (40 total), top 25:

Ligand	Action	Affinity	Parameter
arvanil	Agonist	9.6	pEC50
AMG517	Channel blocker	9.0	pIC50
[3H]A778317	Channel blocker	8.5	pKd
resiniferatoxin	Agonist	8.4	pEC50
[125I]resiniferatoxin	Antagonist	8.4	pIC50
5’-iodoresiniferatoxin	Channel blocker	8.4	pIC50
AMG628	Channel blocker	8.4	pIC50
A425619	Channel blocker	8.3	pIC50
A778317	Channel blocker	8.3	pIC50
SB366791	Channel blocker	8.24	pIC50
asivatrep	Antagonist	8.21	pIC50
A-1165442	Antagonist	8.05	pIC50
6-iodo-nordihydrocapsaicin	Channel blocker	8.0	pIC50
JYL1421	Antagonist	8.0	pIC50
JNJ17203212	Antagonist	7.8	pIC50
AMG 9810	Inhibition	7.8	pIC50
olvanil	Agonist	7.7	pEC50
SB452533	Antagonist	7.7	pKB
mavatrep	Antagonist	7.64	pIC50
AZD1386	Inhibition	7.6	pIC50
zucapsaicin	Activation	7.55	pEC50
BCTC	Antagonist	7.5	pIC50
capsaicin	Agonist	7.5	pEC50
capsazepine	Antagonist	7.4	pIC50
SB705498	Antagonist	7.1	pIC50

Binding affinities (BindingDB)

1467 measured of 1585 human assays (1625 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(3-bromo-4-hydroxy-5-methoxyphenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]acetamide	KI	0.1 nM	US-8791268: Vanilloid receptor ligands, pharmaceutical compositions containing them, process for making them, and use thereof for treating pain and other conditions
(2S)-N-[[3-tert-butyl-1-(3-chlorophenyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	KI	0.1 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands
1-((2-(tert-butyl)-4-(3-chlorophenyl)thiazol-5-yl)methyl)-3-(isoquinolin-5- yl)urea	KI	0.1 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacyclo[11.4.1.0^{1,10}.0^{2,6}.0^{11,15}]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)prop-2-enoate	EC50	0.15 nM
2-(3,5-dibromo-4-hydroxyphenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]acetamide	KI	0.3 nM	US-8791268: Vanilloid receptor ligands, pharmaceutical compositions containing them, process for making them, and use thereof for treating pain and other conditions
N-[[3-tert-butyl-1-(3-chlorophenyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	KI	0.3 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands
N-{6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl}quinolin-7-amine	IC50	0.3 nM
N-((4-(3-chlorophenyl)-2-(trifluoromethyl)thiazol-5-yl)methyl)-2-(5-fluoro-6-(hydroxymethyl)pyridin-3-yl)propanamide	KI	0.3 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
(2R)-N-(6-chloro-1,3-benzothiazol-2-yl)-4-[5-[(1R)-1,2-dihydroxyethyl]-3-fluoro-2-pyridinyl]-2-methylpiperazine-1-carboxamide	IC50	0.4 nM	US-9273043: TRPV1 antagonists including dihydroxy substituent and uses thereof
(2R)-4-[5-[(1R)-1,2-dihydroxyethyl]-3-fluoro-2-pyridinyl]-2-methyl-N-(6-methyl-1,3-benzothiazol-2-yl)piperazine-1-carboxamide	IC50	0.4 nM	US-9273043: TRPV1 antagonists including dihydroxy substituent and uses thereof
N-((4-(3-chlorophenyl)-2-(trifluoromethyl)thiazol-5-yl)methyl)-2-(6-((2-hydroxyethyl)amino)pyridin-3-yl)propanamide	KI	0.4 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
RESINIFERATOXIN	KI	0.48 nM
N-[[3-tert-butyl-1-(3-chloro-4-fluorophenyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	KI	0.5 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands
N-(4-tert-butylphenyl)-4-[3-chloro-5-(5-methyl-1,3,4-oxadiazol-2-yl)-2-pyridinyl]-3,6-dihydro-2H-pyridine-1-carboxamide	IC50	0.5 nM	US-9156830: Heterocyclic compounds
(2R)-4-[5-[(1R)-1,2-dihydroxyethyl]-3-fluoro-2-pyridinyl]-N-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazine-1-carboxamide	IC50	0.6 nM	US-9273043: TRPV1 antagonists including dihydroxy substituent and uses thereof
N-((2-(tert-butyl)-4-(3-chlorophenyl)thiazol-5-yl)methyl)-2-(3-fluoro-4-(methylsulfonamido-methyl)phenyl)propanamide	KI	0.6 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
N-[4-({6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl}oxy)-1,3-benzothiazol-2-yl]acetamide	IC50	0.62 nM
[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacyclo[11.4.1.0^{1,10}.0^{2,6}.0^{11,15}]octadeca-3,8-dien-8-yl]methyl 2-(acetyloxy)-2-(4-hydroxy-3-methoxyphenyl)acetate	EC50	0.65 nM
2-(4-amino-3,5-dibromophenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]acetamide	KI	0.7 nM	US-8791268: Vanilloid receptor ligands, pharmaceutical compositions containing them, process for making them, and use thereof for treating pain and other conditions
N-((4-(3-chlorophenyl)-2-(trifluoromethyl)thiazol-5-yl)methyl)-2-(4-((sulfamoylamino)methyl)-phenyl)propanamide	KI	0.7 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
N-((4-(3-chlorophenyl)-2-(trifluoromethyl)oxazol-5-yl)methyl)-2-(6-((2-hydroxyethyl)amino)pyridin-3-yl)propanamide	KI	0.7 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
13-benzyl-6-hydroxy-15-isopropenyl-4,17-dimethyl-5-oxo-(1R,6R,13S,15R,17R)-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-ylmethyl 2-(4-hydroxy-2-iodo-5-methoxyphenyl)acetate	KI	0.71 nM
4-[1-[[1-(3-chlorophenyl)-3-(trifluoromethyl)pyrazol-5-yl]methylamino]-1-oxopropan-2-yl]-N-(4-fluorophenyl)benzamide	KI	0.8 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands
3-amino-5-({6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl}oxy)-1,2-dihydroquinoxalin-2-one	IC50	0.8 nM
N-(4-tert-butylphenyl)-4-[3-chloro-5-[(1S)-1,2-dihydroxyethyl]-2-pyridinyl]piperazine-1-carboxamide	IC50	0.8 nM	US-9365563: TRPV1 antagonists including dihydroxy substituent and uses thereof
2-(4-amino-3,5-dibromophenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	KI	0.9 nM	US-8791268: Vanilloid receptor ligands, pharmaceutical compositions containing them, process for making them, and use thereof for treating pain and other conditions
N-(4-tert-butylphenyl)-4-[5-[(1S)-1,2-dihydroxyethyl]-3-fluoro-2-pyridinyl]-3,6-dihydro-2H-pyridine-1-carboxamide	IC50	0.9 nM	US-9365563: TRPV1 antagonists including dihydroxy substituent and uses thereof
[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacyclo[11.4.1.0^{1,10}.0^{2,6}.0^{11,15}]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)propanoate	EC50	0.98 nM
1-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-3-[4-[(sulfamoylamino)methyl]phenyl]urea	KI	1 nM	US-8765733: Amine substituted methanesulfonamide derivatives as vanilloid receptor ligands
1-[3-fluoro-4-[(sulfamoylamino)methyl]phenyl]-3-[[6-methyl-2-(4-methylpiperidin-1-yl)-3-pyridinyl]methyl]urea	KI	1 nM	US-8765733: Amine substituted methanesulfonamide derivatives as vanilloid receptor ligands
4-[3-chloro-5-[(2R)-2,3-dihydroxypropyl]-2-pyridinyl]-N-(6-fluoro-1,3-benzothiazol-2-yl)-2-methoxypiperazine-1-carboxamide	IC50	1 nM	US-8921373: Compounds having TRPV1 antagonistic activity and uses thereof
1-(1-methyl-2-oxo-3,4-dihydroquinazolin-5-yl)-3-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydrochromen-4-yl]urea	IC50	1 nM	US-8969325: TRPV1 antagonists
4-[5-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-3-methyl-2-pyridinyl]-N-[3-methyl-4-(trifluoromethyl)phenyl]-3,6-dihydro-2H-pyridine-1-carboxamide	IC50	1 nM	US-9156830: Heterocyclic compounds
2-(3,5-dibromo-4-hydroxyphenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	KI	1.1 nM	US-8791268: Vanilloid receptor ligands, pharmaceutical compositions containing them, process for making them, and use thereof for treating pain and other conditions
N-(4-tert-butylphenyl)-4-[3-chloro-5-[(1S)-1,2-dihydroxyethyl]-2-pyridinyl]-3,6-dihydro-2H-pyridine-1-carboxamide	IC50	1.1 nM	US-9365563: TRPV1 antagonists including dihydroxy substituent and uses thereof
N-((4-(3-chlorophenyl)-2-(trifluoromethyl)thiazol-5-yl)methyl)-2-(5-fluoro-6-(2-(methylsulfonyl)ethyl)pyridin-3-yl)propanamide	KI	1.1 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
N-[[3-tert-butyl-1-(3-chlorophenyl)pyrazol-5-yl]methyl]-2-[3,5-difluoro-4-(methanesulfonamido)phenyl]propanamide	KI	1.2 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands
N-((4-(3-chlorophenyl)-2-(trifluoromethyl)thiazol-5-yl)methyl)-2-(3-fluoro-4-(2-hydroxyethyl)phenyl)-propanamide	KI	1.4 nM	US-9771359: Substituted oxazole- and thiazole-based carboxamide and urea derivatives as vanilloid receptor ligands II
13-benzyl-6-hydroxy-15-isopropenyl-4,17-dimethyl-5-oxo-(1R,6R,13S,15R,17R)-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-ylmethyl 2-(4-hydroxy-2-iodo-3-methoxyphenyl)acetate	KI	1.4 nM
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
13-benzyl-6-hydroxy-15-isopropenyl-4,17-dimethyl-5-oxo-(1R,6R,13S,15R,17R)-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-ylmethyl 2-(2-iodo-5-methoxy-4-methylcarbonyloxyphenyl)acetate	KI	1.5 nM
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
N-[6-(4-tert-butylphenyl)pyrimidin-4-yl]quinolin-7-amine	IC50	1.9 nM
1-(6-fluoro-3-methylisoquinolin-5-yl)-3-[(1R,3S)-3-(3-fluorophenyl)cyclopentyl]urea	IC50	2 nM	US-8802711: TRPV1 antagonists
2-(2-methylpyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)-2-pyridinyl]-5,6,8,9-tetrahydropyrimido[4,5-d]azepin-4-amine	IC50	2 nM	US-9422293: Tetrahydro-pyrimidoazepines as modulators of TRPV1
(2S)-N-[[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	KI	2.1 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands
4-[2-chloro-4-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]-N-[3-methyl-4-(trifluoromethyl)phenyl]-3,6-dihydro-2H-pyridine-1-carboxamide	IC50	2.1 nM	US-9156830: Heterocyclic compounds
1-isoquinolin-5-yl-3-{[4-(trifluoromethyl)phenyl]methyl}urea	EC50	2.1 nM
2-(1,3-dimethyl-2,4-dioxo-4a,7a-dihydrofuro[2,3-d]pyrimidin-5-yl)-N-[4-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide	IC50	2.15 nM	US-9186360: Treatment of respiratory disorders using TRPA1 antagonists
N-[[3-tert-butyl-1-(3-chlorophenyl)pyrazol-5-yl]methyl]-2-[4-(methanesulfonamido)-3-methoxyphenyl]propanamide	KI	2.2 nM	US-9120756: Substituted phenylureas and phenylamides as vanilloid receptor ligands

ChEMBL bioactivities

5181 potent at pChembl≥5 of 5338 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL2177429
10.72	EC50	0.019	nM	RESINIFERATOXIN
10.70	Ki	0.02	nM	CHEMBL3393837
10.70	Ki	0.02	nM	CHEMBL3407762
10.70	Ki	0.02	nM	CHEMBL2177428
10.52	Ki	0.03	nM	CHEMBL3627950
10.52	Ki	0.03	nM	CHEMBL3627723
10.40	Ki	0.04	nM	CHEMBL3407765
10.40	Ki	0.04	nM	CHEMBL3689037
10.30	Ki	0.05	nM	CHEMBL2442912
10.00	Ki	0.1	nM	CHEMBL3314406
10.00	Ki	0.1	nM	CHEMBL3314407
10.00	Ki	0.1	nM	CHEMBL3314409
10.00	Ki	0.1	nM	CHEMBL3314411
10.00	Ki	0.1	nM	CHEMBL3427109
10.00	Ki	0.1	nM	CHEMBL3681230
10.00	Ki	0.1	nM	CHEMBL3689037
10.00	Ki	0.1	nM	CHEMBL3689046
10.00	Ki	0.1	nM	CHEMBL4104073
10.00	Ki	0.1	nM	CHEMBL4215829
10.00	Ki	0.1	nM	CHEMBL4242293
10.00	Ki	0.1	nM	CHEMBL5926013
9.96	IC50	0.11	nM	CHEMBL228451
9.92	Ki	0.12	nM	CHEMBL104647
9.82	IC50	0.15	nM	CHEMBL441472
9.82	EC50	0.15	nM	CHEMBL594016
9.80	IC50	0.1585	nM	CHEMBL1761696
9.74	IC50	0.18	nM	CHEMBL441472
9.70	Ki	0.2	nM	CHEMBL2178059
9.70	Ki	0.2	nM	CHEMBL2177441
9.70	Ki	0.2	nM	CHEMBL2177440
9.70	Ki	0.2	nM	CHEMBL2177429
9.70	Ki	0.2	nM	CHEMBL2178063
9.70	Ki	0.2	nM	CHEMBL3317476
9.70	Ki	0.2	nM	CHEMBL3314377
9.70	Ki	0.2	nM	CHEMBL3314393
9.70	Ki	0.2	nM	CHEMBL3314404
9.70	Ki	0.2	nM	CHEMBL3314405
9.70	Ki	0.2	nM	CHEMBL3314408
9.70	Ki	0.2	nM	CHEMBL3314410
9.70	Ki	0.2	nM	CHEMBL3314389
9.70	Ki	0.2	nM	CHEMBL3393837
9.70	Ki	0.2	nM	CHEMBL4125690
9.70	IC50	0.2	nM	CHEMBL1214342
9.68	IC50	0.21	nM	CHEMBL1092853
9.64	Ki	0.23	nM	CHEMBL2177428
9.64	IC50	0.23	nM	CHEMBL1214342
9.60	Ki	0.25	nM	CHEMBL3427109
9.57	IC50	0.27	nM	CHEMBL4781687
9.54	Ki	0.29	nM	CHEMBL2385408

PubChem BioAssay actives

3356 with measured affinity, of 6100 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
N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]-3-phenylpropanamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
N-[[2-cyclopentylsulfanyl-4-(trifluoromethyl)phenyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1253971: Antagonist activity at human TRPV1 heterologously expressed in CHO cells assessed as inhibition of NADA-induced activation by FLIPR assay	ki	<0.0001	uM
N-[[2-(benzenesulfonamido)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1281559: Displacement of [3H]RTX from human TRPV1 expressed in CHO cells after 60 mins by scintillation counting analysis	ki	<0.0001	uM
N-[[2-butoxy-6-[chloro(difluoro)methyl]-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1198234: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of N-arachidonoyl dopamine-induced activity by FLIPR assay	ki	<0.0001	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	1198234: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of N-arachidonoyl dopamine-induced activity by FLIPR assay	ki	<0.0001	uM
N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]-2-(2-methylphenyl)acetamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]-3-(4-fluorophenyl)propanamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-3-(4-methylphenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]-2-methylbutanamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
2-cyclohexyl-N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]acetamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
1-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]cyclopentane-1-carboxamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-1-[3-fluoro-4-(methanesulfonamido)phenyl]cyclopentane-1-carboxamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	<0.0001	uM
[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl (4-hydroxy-3-iodo-5-methoxyphenyl) carbonate	452447: Agonist activity at human TRPV1 expressed in HEK293 cells assessed as increase in intracellular calcium level	ec50	<0.0001	uM
[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate	292699: Agonist activity at human recombinant TRPV1 expressed in human HEK293 cells	ec50	<0.0001	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-phenylmethoxy-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	750802: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as inhibition of N-arachidonoyldopamine-induced activity after 5 mins by FLIPR assay	ki	<0.0001	uM
N-[[6-[chloro(difluoro)methyl]-2-cyclopentyloxy-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1198234: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of N-arachidonoyl dopamine-induced activity by FLIPR assay	ki	<0.0001	uM
(2S)-N-[[3-tert-butyl-1-(3-chlorophenyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1365092: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of NADA-induced intracellular calcium level preincubated with cells followed by NADA addition by Fluo-4 dye based FLIPR assay	ki	<0.0001	uM
1-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-3-quinolin-4-ylurea	1190831: Antagonist activity at human TRPV1 assessed as inhibition of capsaicin-induced effect by FLIPR assay	ki	<0.0001	uM
1-isoquinolin-5-yl-3-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]urea	1190834: Antagonist activity at human TRPV1 assessed as inhibition of NADA-induced effect at 1 uM by FLIPR assay	ki	<0.0001	uM
1-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-3-quinazolin-6-ylurea	1190831: Antagonist activity at human TRPV1 assessed as inhibition of capsaicin-induced effect by FLIPR assay	ki	<0.0001	uM
(2S)-2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	705234: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as inhibition of N-acetyldopamine-induced activity after 5 mins by FLIPR assay	ki	<0.0001	uM
1-[(4-tert-butylphenyl)methyl]-3-[[4-(methanesulfonamido)phenyl]methyl]thiourea	2032628: Antagonist activity at TRPV1 (unknown origin)	ic50	0.0001	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-[(3R)-3-methylcyclohexen-1-yl]-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0001	uM
N-[[2-(4-ethylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0001	uM
(2S)-N-[[2-(4-tert-butylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0001	uM
(2S)-N-[[2-(4,4-dimethylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0001	uM
N-[[6-tert-butyl-2-(4-ethylpiperidin-1-yl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1456276: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as inhibition of capsaicin induced calcium influx pretreated for 6 mins followed by capsaicin addition by Fluo-4/Pluronic F127 probe based FLIPR method	ki	0.0001	uM
(2S)-N-[[3-tert-butyl-1-(3-chloro-4-fluorophenyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1365091: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced intracellular calcium level preincubated for 6 mins followed by capsaicin addition by Fluo-4 dye based FLIPR assay	ki	0.0001	uM
2-(4-amino-3,5-dichlorophenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]acetamide	1398828: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as reduction in NADA-induced intracellular calcium level preincubated with cells followed by NADA addition measured after 5 mins by Fluo-4 dye based FLIPR assay	ki	0.0001	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-2-(3-methylphenyl)-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]acetamide	1206943: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	0.0001	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-[[2-(4-hydroxy-3-methoxyphenyl)acetyl]oxymethyl]-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] 2-phenylacetate	159554: Inhibitory constant for RTX binding to porcine spinal cord	ki	0.0001	uM
[(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)prop-2-enoate	452447: Agonist activity at human TRPV1 expressed in HEK293 cells assessed as increase in intracellular calcium level	ec50	0.0001	uM
(2S)-N-[[1-(3-chlorophenyl)-3-(trifluoromethyl)pyrazol-5-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1365091: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced intracellular calcium level preincubated for 6 mins followed by capsaicin addition by Fluo-4 dye based FLIPR assay	ki	0.0001	uM
(2S)-N-[[2-cyclohexylsulfanyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	779368: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as inhibition of N-acetyldopamine-induced activity after 5 mins by FLIPR assay	ki	0.0001	uM
(2S)-N-[[2-(4-ethylcyclohexyl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
(2S)-2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-(3-methylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
N-[[2-(4-tert-butylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
N-[[2-(4,4-dimethylcyclohexen-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
2-[3,5-difluoro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	1498366: Antagonist activity at recombinant human TRPV1 expressed in CHOK1 cells assessed as reduction in capsaicin-induced Ca2+ flux after 15 mins by fluo-4-based FLIPR assay	ki	0.0002	uM
N-[[2-(dipropylamino)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1253972: Antagonist activity at human TRPV1 heterologously expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	0.0002	uM
N-[[2-(4-benzylpiperidin-1-yl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1253972: Antagonist activity at human TRPV1 heterologously expressed in CHO cells assessed as inhibition of capsaicin-induced activation by FLIPR assay	ki	0.0002	uM
N-[[2-(3-chloro-4-fluorophenyl)-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1183019: Antagonist activity against human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced channel activation by FLIPR assay	ki	0.0002	uM
N-[[2-chloro-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180186: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of capsaicin-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
N-[4-(trifluoromethyl)phenyl]-7-[3-(trifluoromethyl)-2-pyridinyl]pteridin-4-amine	476738: Antagonist activity at human recombinant TRPV1 expressed in HEK293 cells assessed as inhibition of capsazepine-induced calcium mobilization by FLIPR assay	ic50	0.0002	uM
3-[3-(trifluoromethyl)-2-pyridinyl]-N-[5-(trifluoromethyl)-2-pyridinyl]pyrido[2,3-b]pyrazin-8-amine	476738: Antagonist activity at human recombinant TRPV1 expressed in HEK293 cells assessed as inhibition of capsazepine-induced calcium mobilization by FLIPR assay	ic50	0.0002	uM
N-[(1R,3S)-3-hydroxycyclohexyl]-5-[4-(trifluoromethyl)phenyl]-4-[[[(2S)-1,1,1-trifluoropropan-2-yl]amino]methyl]-1,2-oxazole-3-carboxamide	590918: Antagonist activity at human TRPV1 expressed in CHO-K1 cells assessed as inhibition of capsaicin-induced intracellular Ca2+ influx by FLIPR assay	ic50	0.0002	uM
N-[[2-cyclohexyl-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	1180189: Antagonist activity at human TRPV1 expressed in CHO cells assessed as inhibition of N-arachidonoyl dopamine-induced increase in intracellular Ca2+ level by FLIPR assay	ki	0.0002	uM
2-[3-fluoro-4-(methanesulfonamido)phenyl]-N-[[2-[4-[(4-methylphenyl)methyl]piperidin-1-yl]-6-(trifluoromethyl)-3-pyridinyl]methyl]propanamide	705238: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as inhibition of capsaicin-induced activity by FLIPR assay	ki	0.0002	uM
N-[[2-[4-[(3,4-difluorophenyl)methyl]piperidin-1-yl]-6-(trifluoromethyl)-3-pyridinyl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide	705238: Antagonist activity at human TRPV1 expressed in CHOK1 cells assessed as inhibition of capsaicin-induced activity by FLIPR assay	ki	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Capsaicin	increases response to substance, increases activity, increases reaction, decreases reaction, affects reaction (+8 more)	35
Calcium	decreases reaction, increases activity, increases import, affects reaction, affects import (+4 more)	13
capsazepine	affects binding, decreases activity, decreases reaction, increases abundance, increases activity (+3 more)	8
anandamide	increases reaction, increases uptake, affects binding, increases activity, affects reaction (+3 more)	5
nonivamide	increases activity, increases abundance, increases expression, increases phosphorylation, increases response to substance (+1 more)	4
iodoresiniferatoxin	decreases reaction, increases uptake, affects reaction, affects binding, decreases activity (+3 more)	4
Cannabidiol	decreases secretion, increases reaction, affects binding, decreases reaction, increases uptake (+3 more)	4
arachidonyl dopamine	increases activity, increases response to substance, decreases reaction, increases reaction, increases uptake	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Valproic Acid	affects cotreatment, decreases expression	3
acetosulfame	increases activity	2
resiniferatoxin	increases uptake, increases activity, increases abundance, affects binding, decreases reaction	2
N-(4-hydroxyphenyl)arachidonylamide	affects binding, decreases reaction, increases activity	2
N-oleoyldopamine	decreases reaction, increases reaction, increases uptake, increases activity	2
3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide	affects binding, decreases activity, decreases reaction, increases reaction, increases uptake (+1 more)	2
bisphenol S	decreases methylation, affects cotreatment, decreases expression	2
Aspartame	increases activity	2
Vehicle Emissions	affects response to substance, increases abundance, increases expression, increases reaction	2
Cyclamates	increases activity	2
Colforsin	increases activity, increases reaction	2
Hydrogen Peroxide	decreases reaction, increases expression, affects expression	2
Quercetin	decreases expression, increases expression	2
Saccharin	increases activity	2
Smoke	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	decreases reaction, increases activity, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
1-Methyl-3-isobutylxanthine	increases reaction, affects cotreatment, decreases expression, increases activity	2
Cyclosporine	decreases expression	2
Copper Sulfate	decreases expression, increases activity	2
Particulate Matter	decreases reaction, increases expression, increases phosphorylation, affects response to substance, increases abundance	2

ChEMBL screening assays

674 unique, capped per target: 506 binding, 166 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1014666	Functional	Antagonist activity at human TRPV1 expressed in HEK293 cells assessed as inhibition of capsaicin-induced calcium flux	Identification and synthesis of 2,7-diamino-thiazolo[5,4-d]pyrimidine derivatives as TRPV1 antagonists. — Bioorg Med Chem Lett
CHEMBL1026729	Binding	Inhibition of Vanilloid receptor 1	Biologically active compounds from Aphyllophorales (polypore) fungi. — J Nat Prod
CHEMBL4680537	ADMET	Activation of human TRPV1 expressed in HEK293T cells preincubated for 5 mins followed by CaCl2 addition by calcium-5 fluorescence dye based FLIPR assay	Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor — RSC Med Chem

Cellosaurus cell lines

7 cell lines: 4 transformed cell line, 1 spontaneously immortalized cell line, 1 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1F92	CHO-hTRPV1	Spontaneously immortalized cell line	Female
CVCL_C9GY	WAe009-A-U	Embryonic stem cell	Female
CVCL_D1JB	PrecisION hTRPV1-HEK	Transformed cell line	Female
CVCL_D6A6	HyCyte HEK293T KO-hTRPV1	Transformed cell line	Female
CVCL_D8FF	Ubigene Caco-2 TRPV1 KO	Cancer cell line	Male
CVCL_E5JE	HEK293/TRPV1	Transformed cell line	Female
CVCL_E9Y4	HEK293-TRPV1-RFP	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00657748	PHASE2	WITHDRAWN	Lithium and Acetate for Canavan Disease
NCT05527379	Not specified	COMPLETED	Interest of Virtual Reality to Reduce Patient Anxiety During the Placement of a Percutaneous Implantable Port Catheter
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04833907	PHASE1/PHASE2	ENROLLING_BY_INVITATION	rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease
NCT04998396	PHASE1/PHASE2	RECRUITING	A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial)
NCT00724802	Not specified	UNKNOWN	Oral Glyceryl Triacetate (GTA) in Newborns With Canavan
NCT01999257	Not specified	COMPLETED	Efficacy Study of an Online Educational Module Before Carrier Genetic Screening in Persons of Ashkenazi Jewish Descent.
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02851563	Not specified	COMPLETED	A Natural History Study of Canavan Disease
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04126005	Not specified	COMPLETED	Natural History Study of Patients With Canavan Disease (CANinform Study)
NCT05317780	Not specified	NO_LONGER_AVAILABLE	Canavan-Single Patient IND
NCT01624558	Not specified	WITHDRAWN	Effectiveness of Carbon Filters to Reduce the Anesthetic Gas Concentration in an Anesthetized Patient
NCT02561598	Not specified	WITHDRAWN	A Case Control Study of Patients With Diagnosis of Malignant Hyperthermia
NCT02964481	Not specified	TERMINATED	Malignant Hyperthermia Registry and Genetic Testing
NCT03964870	Not specified	UNKNOWN	Spanish Registry of RYR1 and CACNA1S Polymorphisms
NCT04474860	Not specified	UNKNOWN	Gene Mutation Spectrum of Malignant Hyperthermia in China
NCT04610619	Not specified	UNKNOWN	Multisystem Features of Malignant Hyperthermia or Rhabdomyolysis Related to RYR1 Variants
NCT05036148	Not specified	COMPLETED	Malignant Hyperthermia in Czech Republic: Description of the Biggest Slavonic Group of Patients Investigated for Risk of Malignant Hyperthermia
NCT05402839	Not specified	RECRUITING	Screening of Malignant Hyperthermia Susceptible Individuals
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease