Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTELV3W)

DTT Name Transformation-sensitive protein p120 (TRPA1)
Synonyms TRPA1; Ankyrin-like with transmembrane domains protein 1; ANKTM1
Gene Name TRPA1
DTT Type
Successful target
 [1]
BioChemical Class
Transient receptor potential catioin channel
UniProt ID
TRPA1_HUMAN
TTD ID
T84040
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MKRSLRKMWRPGEKKEPQGVVYEDVPDDTEDFKESLKVVFEGSAYGLQNFNKQKKLKRCD
DMDTFFLHYAAAEGQIELMEKITRDSSLEVLHEMDDYGNTPLHCAVEKNQIESVKFLLSR
GANPNLRNFNMMAPLHIAVQGMNNEVMKVLLEHRTIDVNLEGENGNTAVIIACTTNNSEA
LQILLKKGAKPCKSNKWGCFPIHQAAFSGSKECMEIILRFGEEHGYSRQLHINFMNNGKA
TPLHLAVQNGDLEMIKMCLDNGAQIDPVEKGRCTAIHFAATQGATEIVKLMISSYSGSVD
IVNTTDGCHETMLHRASLFDHHELADYLISVGADINKIDSEGRSPLILATASASWNIVNL
LLSKGAQVDIKDNFGRNFLHLTVQQPYGLKNLRPEFMQMQQIKELVMDEDNDGCTPLHYA
CRQGGPGSVNNLLGFNVSIHSKSKDKKSPLHFAASYGRINTCQRLLQDISDTRLLNEGDL
HGMTPLHLAAKNGHDKVVQLLLKKGALFLSDHNGWTALHHASMGGYTQTMKVILDTNLKC
TDRLDEDGNTALHFAAREGHAKAVALLLSHNADIVLNKQQASFLHLALHNKRKEVVLTII
RSKRWDECLKIFSHNSPGNKCPITEMIEYLPECMKVLLDFCMLHSTEDKSCRDYYIEYNF
KYLQCPLEFTKKTPTQDVIYEPLTALNAMVQNNRIELLNHPVCKEYLLMKWLAYGFRAHM
MNLGSYCLGLIPMTILVVNIKPGMAFNSTGIINETSDHSEILDTTNSYLIKTCMILVFLS
SIFGYCKEAGQIFQQKRNYFMDISNVLEWIIYTTGIIFVLPLFVEIPAHLQWQCGAIAVY
FYWMNFLLYLQRFENCGIFIVMLEVILKTLLRSTVVFIFLLLAFGLSFYILLNLQDPFSS
PLLSIIQTFSMMLGDINYRESFLEPYLRNELAHPVLSFAQLVSFTIFVPIVLMNLLIGLA
VGDIAEVQKHASLKRIAMQVELHTSLEKKLPLWFLRKVDQKSTIVYPNKPRSGGMLFHIF
CFLFCTGEIRQEIPNADKSLEMEILKQKYRLKDLTFLLEKQHELIKLIIQKMEIISETED
DDSHCSFQDRFKKEQMEQRNSRWNTVLRAVKAKTHHLEP
Function
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)- tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system.
KEGG Pathway
Inflammatory mediator regulation of TRP channels (hsa04750 )
Reactome Pathway
TRP channels (R-HSA-3295583 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Menthol DMG2KW7 Back pain ME84.Z Approved [1]
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2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
LY3526318 DMFXNQM Chronic low-back pain MG30 Phase 2 [2]
HX-100 DMFRM15 Diabetic neuropathy 8C0Z Phase 1 [3]
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44 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
1'-acetoxychavicol acetate DMMP7HU Discovery agent N.A. Investigative [4]
1,6-hexamethylene diisocyanate DMLB3RT Discovery agent N.A. Investigative [5]
2-methyl-1-(pyridin-3-yl)pent-1-en-3-one oxime DMRWOQH Discovery agent N.A. Investigative [6]
2-methyl-1-(pyridin-4-yl)pent-1-en-3-one oxime DMTQ4FV Discovery agent N.A. Investigative [6]
2-methyl-1-(thiophen-2-yl)pent-1-en-3-one oxime DMLTJDR Discovery agent N.A. Investigative [6]
2-methyl-1-(thiophen-3-yl)pent-1-en-3-one oxime DMQJKSV Discovery agent N.A. Investigative [6]
2-pentenal DM032YM Discovery agent N.A. Investigative [7]
3-Methyl-4-phenylbut-3-en-2-one oxime DM0WVTF Discovery agent N.A. Investigative [8]
4-oxo-nonenal DMPX1J9 Discovery agent N.A. Investigative [9]
A-967079 DMOY7TF Pain MG30-MG3Z Investigative [10]
acetaldehyde DMJFKG4 Discovery agent N.A. Investigative [11]
acrolein DMAMCSR Discovery agent N.A. Investigative [12]
AMG-2504 DMRD83Q Discovery agent N.A. Investigative [6]
AMG-5445 DMNEVXT Discovery agent N.A. Investigative [6]
AMG-7160 DMEVNZI Discovery agent N.A. Investigative [6]
AMG-9090 DM1J46S Discovery agent N.A. Investigative [6]
artepillin C DMWCDM8 Discovery agent N.A. Investigative [13]
benzyl bromide DM857X2 Discovery agent N.A. Investigative [5]
bromoacetone DMTBO7F Discovery agent N.A. Investigative [5]
chlorobenzylidene malononitrile DMLF7MK Discovery agent N.A. Investigative [14]
chloropicrin DMSGBQA Discovery agent N.A. Investigative [5]
cinnamaldehyde DMZDUXG Discovery agent N.A. Investigative [15]
crotylaldehyde DMTWRQI Discovery agent N.A. Investigative [16]
dibenzoxazepine DMD8TWC Discovery agent N.A. Investigative [14]
dibutyl phthalate DMEDGKO Discovery agent N.A. Investigative [17]
Formaldehyde DM7Q6M0 Discovery agent N.A. Investigative [18]
gingerol DMNXYSM Discovery agent N.A. Investigative [15]
icilin DMYVOL9 Discovery agent N.A. Investigative [19]
isovelleral DMTRGAP Discovery agent N.A. Investigative [20]
methyl isocyanate DME4JGF Discovery agent N.A. Investigative [5]
methyl p-hydroxybenzoate DMO58UW Discovery agent N.A. Investigative [21]
methyl salicylate DMKCG8H Back pain ME84.Z Investigative [15]
methylglyoxal DMRC3OZ Discovery agent N.A. Investigative [22]
morphanthridine DMB91UL Discovery agent N.A. Investigative [14]
MTSEA DM8KPWM Discovery agent N.A. Investigative [23]
NPPB DMFIWAN Discovery agent N.A. Investigative [24]
oleocanthal DMI1CAJ Discovery agent N.A. Investigative [25]
omega-chloroacetophenone DMGMIX3 Discovery agent N.A. Investigative [14]
PF-4840154 DMI29ED Discovery agent N.A. Investigative [26]
prostaglandin A2 DMWC4X8 Discovery agent N.A. Investigative [27]
resolvin D2 DMLVU6H Discovery agent N.A. Investigative [28]
super cinnamaldehyde DMVZWCI Discovery agent N.A. Investigative [23]
TCS 5861528 DMMUFSQ Discovery agent N.A. Investigative [29]
[3H]resolvin D1 DMFT0HU Discovery agent N.A. Investigative [30]
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⏷ Show the Full List of 44 Investigative Drug(s)

References

1 TRPV1-mediated itch in seasonal allergic rhinitis. Allergy. 2009 May;64(5):807-10.
2 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Galangal pungent component, 1'-acetoxychavicol acetate, activates TRPA1. Biosci Biotechnol Biochem. 2010;74(8):1694-6.
5 Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J. 2009 Apr;23(4):1102-14.
6 Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. J Med Chem. 2010 Jul 22;53(14):5085-107.
7 Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents. J Med Chem. 2010 Jul 22;53(14):5085-107.
8 Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor. Bioorg Med Chem Lett. 2010 Jan 1;20(1):276-9.
9 Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008 Mar 5;28(10):2485-94.
10 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 485).
11 Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci. 2007 Nov;26(9):2516-23.
12 TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006 Mar 24;124(6):1269-82.
13 Artepillin C, a major ingredient of Brazilian propolis, induces a pungent taste by activating TRPA1 channels. PLoS One. 2012;7(11):e48072.
14 Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor. Toxicol Appl Pharmacol. 2008 Sep 1;231(2):150-6.
15 Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004 Mar 25;41(6):849-57.
16 Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest. 2008 Jul;118(7):2574-82.
17 TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity. J Neuroimmunol. 2009 Feb 15;207(1-2):66-74.
18 An ion channel essential for sensing chemical damage. J Neurosci. 2007 Oct 17;27(42):11412-5.
19 ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003 Mar 21;112(6):819-29.
20 TRPA1 mediates the noxious effects of natural sesquiterpene deterrents. J Biol Chem. 2008 Aug 29;283(35):24136-44.
21 Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels. Br J Pharmacol. 2007 May;151(1):153-60.
22 Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy. Pharmacol Res. 2012 Jan;65(1):149-58.
23 Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature. 2007 Feb 1;445(7127):541-5.
24 NPPB structure-specifically activates TRPA1 channels. Biochem Pharmacol. 2010 Jul 1;80(1):113-21.
25 Unusual pungency from extra-virgin olive oil is attributable to restricted spatial expression of the receptor of oleocanthal. J Neurosci. 2011 Jan 19;31(3):999-1009.
26 Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9.
27 Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12045-50.
28 Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: distinct roles of resolvin D1, D2, and E1.J Neurosci. 2011 Dec 14;31(50):18433-8.
29 Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals. Anesthesiology. 2009 Jul;111(1):147-54.
30 Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br J Pharmacol. 2010 Oct;161(3):707-20.