TRPA1

Synonyms

Ankyrin-like with transmembrane domains protein 1, ANKTM1, TRPA1, Ankyrin-Like With Transmembrane Domains 1, Transformation-Sensitive Protein P120, FEPS1, FEPS, TRPA1 Cation Channel, Wasabi Receptor, Transient Receptor Potential Cation Channel Subfamily A Member 1, Transient Receptor Potential Cation Channel, Subfamily A, Member 1

Description

TRPA1 (Transient receptor potential cation channel subfamily A member 1) involved in receptor-activated non-selective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function. Shows 8-fold preference for divalent over monovalent cations. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of irritants, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as an ionotropic cannabinoid receptor by being activated by delta-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Is activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds. Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner, whereas mechanisms of non-electrophilic ligands are not well determined.

KO Status

F0

Drug Information

Launched drugs: 2
Drugs in clinical trials: 4
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Ibuprofen/Levomenthol

Approved

Menthol

Approved

Stomach Neoplasms, Prostatic Neoplasms, Castration-Resistant, Bronchitis, Sinusitis, Diagnostic agents, Pharyngitis

Bifonazole/Crotamiton/Lidocaine/Glycyrrhetinic Acid/Levomenthol

Approved

Tinea Pedis, Tinea

Methyl Salicylate/Menthol/camphor/Chlorphenamine Maleate

Approved

Menthol/Methyl Salicylate

Approved

Hisamitsu Pharmaceutical Co Inc

Pain

Indometacin/L-menthol

K-285

Phase 2 Clinical

Kowa

Acute Pain

Levomenthol

NPO-13

Phase 2 Clinical

University Hospitals Cleveland Medical Center

Colonic Neoplasms, Colonic Polyps, Intestinal Diseases

GRC-17536

GRC-17536

Phase 2 Clinical

Glenmark Pharmaceuticals Ltd

Diabetic Neuropathies, Asthma, Neuralgia

HX-100

HX-100

Phase 1 Clinical

Hydra Biosciences

Asthma, Neuralgia

Dexamethasone Acetate/camphor/Menthol

IND

Guangdong Hengjian Pharmaceutical Co Ltd

References


Title

Authors

Source

A cell-penetrating scorpion toxin enables mode-specific modulation of TRPA1 and pain

Lin King J.V., Emrick J.J., Kelly M.J.S., Herzig V., King G.F., Medzihradszky K.F., Julius D.,

Cell 178:1362-1374(2019)

N-Cinnamoylanthranilates as human TRPA1 modulators: structure-activity relationships and channel binding sites

Chandrabalan A., McPhillie M.J., Morice A.H., Boa A.N., Sadofsky L.R.,

Eur. J. Med. Chem. 170:141-156(2019)

Structure of the TRPA1 ion channel suggests regulatory mechanisms

Paulsen C.E., Armache J.P., Gao Y., Cheng Y., Julius D.,

Nature 520:511-517(2015)

A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome

Kremeyer B., Lopera F., Cox J.J., Momin A., Rugiero F., Marsh S., Woods C.G., Jones N.G., Paterson K.J., Fricker F.R., Villegas A., Acosta N., Pineda-Trujillo N.G., Ramirez J.D., Zea J., Burley M.W., Bedoya G., Bennett D.L., Wood J.N., Ruiz-Linares A.,

Neuron 66:671-680(2010)

An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts

Jaquemar D., Schenker T., Trueb B.,

J. Biol. Chem. 274:7325-7333(1999)

DNA sequence and analysis of human chromosome 8

Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T., Lander E.S.,

Nature 439:331-335(2006)

TRP channel activation by reversible covalent modification

Hinman A., Chuang H.H., Bautista D.M., Julius D.,

Proc. Natl. Acad. Sci. U.S.A. 103:19564-19568(2006)

Requirement of a soluble intracellular factor for activation of transient receptor potential A1 by pungent chemicals: role of inorganic polyphosphates

Kim D., Cavanaugh E.J.,

J. Neurosci. 27:6500-6509(2007)

TRPA1 underlies a sensing mechanism for O2

Takahashi N., Kuwaki T., Kiyonaka S., Numata T., Kozai D., Mizuno Y., Yamamoto S., Naito S., Knevels E., Carmeliet P., Oga T., Kaneko S., Suga S., Nokami T., Yoshida J., Mori Y.,

Nat. Chem. Biol. 7:701-711(2011)

Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation

Chen J., Joshi S.K., DiDomenico S., Perner R.J., Mikusa J.P., Gauvin D.M., Segreti J.A., Han P., Zhang X.F., Niforatos W., Bianchi B.R., Baker S.J., Zhong C., Simler G.H., McDonald H.A., Schmidt R.G., McGaraughty S.P., Chu K.L., Kym P.R.,

Pain 152:1165-1172(2011)