title: Recent advances in the biology and medicinal chemistry of TRPA1.
abstract: The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is a nonselective cation channel that is highly expressed in small-diameter sensory neurons, where it functions as a polymodal receptor, responsible for detecting potentially harmful chemicals, mechanical forces and temperatures. TRPA1 is also activated and/or sensitized by multiple endogenous inflammatory mediators. As such, TRPA1 likely mediates the pain and neurogenic inflammation caused by exposure to reactive chemicals. In addition, it is also possible that this channel may mediate some of the symptoms of chronic inflammatory conditions such as asthma. We review recent advances in the biology of TRPA1 and summarize the evidence for TRPA1 as a therapeutic drug target. In addition, we provide an update on TRPA1 medicinal chemistry and the progress in the search for novel TRPA1 antagonists.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC, San Diego, CA 92121, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Rech
authors.forename: William A
authors.initials: WA
authors.lastname: Eckert
authors.forename: Michael P
authors.initials: MP
authors.lastname: Maher
authors.forename: Tue
authors.initials: T
authors.lastname: Banke
authors.forename: Anindya
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Alan D
authors.initials: AD
authors.lastname: Wickenden
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000276:immunology / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000639:trends; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D049990:Membrane Transport Modulators / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D049990:Membrane Transport Modulators; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels