Experimental Approach
We developed and applied a novel molecular dynamics approach to identify
the Cav2.2 recognition motif of the core CBD3 peptide as
the A1R2 dipeptide and used its
presenting motif to design pharmacophore models to screen 27 million
compounds in the open access server ZincPharmer. Of 200 curated hits, 77
compounds were assessed using depolarizationāevoked calcium influx in
rat dorsal root ganglion (DRG) neurons. Nine compounds were tested using
electrophysiology and one compound (CBD3063) was evaluated
biochemically, electrophysiologically, and behaviorally effects in a
model of experimental pain: