GNE551 is a potent, selective, non-covalent agonist of TRPA1 ion channel with EC50 of 254 nM in Ca2+ influx assays.
GNE551 (1 μM) evoked outward currents at +80 mV and inward currents at −80 mV in whole-cell recordings assays, and evoked robust currents in TRPA1-expressing cells at 80 mV with EC50 of 141 nM, which could be blocked by 1 uM A-967079.
GNE551 (20 μM) did not activate or block human TRPV1, TRPM8, or TRPC6, did not inhibit human potassium channel hERG1 and sodium channels (hNav1.2., hNav1.5, or hNav1.7) at 10 μM.
GNE551 binds to a transmembrane pocket conserved in several other TRP channels.
Compared to the canonical covalent agonist AITC, GNE551 exhibits remarkable differences in channel modulation, pain response, and sensitivity to inhibitor treatment.
