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. Author manuscript; available in PMC: 2020 Jan 24.
Published in final edited form as: Cell. 2019 Jan 10;176(3):459–467.e13. doi: 10.1016/j.cell.2018.12.011

Figure 6. Molecular docking and pharmacology of designed CB2 agonist/antagonist pair.

Figure 6.

(A) Chemical structures of rationally designed agonist MRI2594 and antagonist/inverse agonist MRI2687. (B) The docking poses of MRI2594 (orange sticks) and MRI2687 (blue sticks) in AM10257-bound CB2 (AM10257 is removed). (C) MRI2594 performs as an agonist of CB2 and MRI2687 performs as an inverse agonist of CB2 as determined by β-arrestin2 recruitment assay. CP55,940 EC50: 2.3 ± 0.6 nM, Emax (fold): 2.3 ± 0.1; MRI2594 EC50: 0.17 ± 0.03 nM, Emax (fold): 2.0 ± 0.2; MRI2687 EC50: 0.24 ± 0.06 nM, Emax (fold): 0.75 ± 0.04; AM10257 EC50: 0.20 ± 0.04 nM, Emax (fold): 0.70 ± 0.05. (D) MRI2594 and MRI2687 perform as an agonist and a partial agonist of CB1 as determined by β-arrestin2 recruitment assay. CP55,940 EC50: 17.9 ± 1.4 nM, Emax (fold): 20.6 ± 0.9 (from Figure 5C); MRI2594 EC50: 310.0 ± 54.0 nM, Emax (fold): 28.0 ± 2.0; MRI2687 EC50: 114.0 ± 15.0 nM, Emax (fold): 6.0 ± 0.3. Data are presented as mean ± s.e.m. of > 4 experiments performed in duplicate.

See also Figures S2 and S6.