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Structure of the GPR139 agonists studied herein. (a) Surrogate agonist 1a from Shi et al.23. (b) Surrogate agonist 7c from Dvorak et al.14, 24. (c,d) Trp and Phe from Isberg et al.16. Coloring denote chemical commonalities (supported by mutations herein); grey: major hydrophobic part, red: polar linkers (1a and 7c) or carboxyls (Phe and Trp), green: hydrophobic element unique for the larger 1a and 7c.
