Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel.

Authors: Thomas Ryckmans, Aisah A Aubdool, Jennifer V Bodkin, Peter Cox, Susan D Brain, Thomas Dupont, Emma Fairman, Yoshinobu Hashizume, Naoko Ishii, Teruhisa Kato, Linda Kitching, Julie Newman, Kiyoyuki Omoto, David Rawson, Jade Strover

Journal, date & volume: , 2011 Jun 21 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21741838

Abstract
TrpA1 is an ion channel involved in nociceptive and inflammatory pain. It is implicated in the detection of chemical irritants through covalent binding to a cysteine-rich intracellular region of the protein. While performing an HTS of the Pfizer chemical collection, a class of pyrimidines emerged as a non-reactive, non-covalently binding family of agonists of the rat and human TrpA1 channel. Given the issues identified with the reference agonist Mustard Oil (MO) in screening, a new, non-covalently binding agonist was optimized and proved to be a superior agent to MO for screening purposes. Compound 16a (PF-4840154) is a potent, selective agonist of the rat and human TrpA1 channel and elicited TrpA1-mediated nocifensive behaviour in mouse.