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. Author manuscript; available in PMC: 2021 Jan 20.
Published in final edited form as: Nat Chem Biol. 2020 Jun 1;16(7):749–755. doi: 10.1038/s41589-020-0549-2

Fig. 1 |. Hit-to-lead optimization, pharmacological characterization and structure of allosteric modulator AS408 bound to β2AR.

Fig. 1 |

a, Salmeterol (orange) extends from the orthosteric site where epinephrine (yellow) binds to an exosite at the extracellular vestibule. The exosite was used as a docking template. b, Hit-to-lead optimization of the docking hit BRAC1. c–f, Negative allosteric effect of BRAC1 (c,d) and AS408 (e,f) on norepinephrine-stimulated β-arrestin 2 (β-ARR) recruitment (c,e) and on cAMP accumulation (d,f). Data are derived from 3–12 experiments done in duplicate and given as mean ± s.e.m.; the sample size (n) is labeled in the figure. g, Structure of AS408 bound to β2AR in the presence of antagonist alprenolol.