(A) Chemical structures of the rationally designed antagonist XIE55 and agonist XIE57.
(B) XIE57 acts as a CB2 agonist while XIE55 behaves as a CB2 antagonist, as determined by cAMP assay. The dose response curves for CP55940, a known agonist, and SR144528, a known inverse agonist, are also shown. CP55940 EC50: 45.5 ± 24 nM, Ki: 1–2 nM; SR144528 EC50: 10.5 ± 4.5 nM, Ki: 0.6 nM; XIE57 EC50: 6.9 ± 2.9 μM, Ki: 639 nM; XIE55 EC50: 1.5 ± 0.4 μM, Ki: 138 nM. Data are presented as mean ± SEM of at least 3 experiments performed in duplicate.
(C) The docking of XIE55 and XIE57 in WIN 55,212–2-bound CB2 structure (WIN 55,212–2 is removed).