- Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel
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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.
- Ryckmans, Thomas,Aubdool, Aisah A.,Bodkin, Jennifer V.,Cox, Peter,Brain, Susan D.,Dupont, Thomas,Fairman, Emma,Hashizume, Yoshinobu,Ishii, Naoko,Kato, Teruhisa,Kitching, Linda,Newman, Julie,Omoto, Kiyoyuki,Rawson, David,Strover, Jade
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p. 4857 - 4859
(2011/09/16)
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