Fig. 4.

Synthesis and functional screen of focused triazole libraries. (A) Generation of five focused libraries with the CuAAC reaction conducted in microplates. (B) The structural representation of five focused libraries. (C) Bioactivity screen of 2,400 crude reaction products from focused libraries. cAMP accumulation was measured in CHO-K1 cells expressing human GLP-1R treated by different reaction products (50 µM) in the presence of EC₅₀ of GLP-1(9-36) (1.12 µM). Hits that potentiated or suppressed the cAMP production above 90% (relative to the full response of GLP-1(9-36) or DMSO control) were labeled in red or yellow. (D) Dose–response curves of six most potent PAMs measured in CHO-K1 cells expressing human GLP-1R in the presence of EC₂₀ of GLP-1(9-36) (0.6 µM). cAMP accumulation was normalized to the full response of BETP. Data represent means ± SEM of three independent experiments performed in triplicate. (E) The structures and pharmacological data of these six PAMs.