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Small molecule bound to diabetes target

The GLP-1 receptor (GLP-1R), similar to other class B G-protein-coupled receptors, is a target for the treatment of metabolic disorders such as obesity and type 2 diabetes. Although how peptide ligands can activate this important therapeutic target is known, how small molecules can do so is less clear. Here, Patrick Sexton and colleagues report the structure of GLP-1R and its G protein in complex with the small molecule TT-OAD2, a candidate for oral administration in the treatment type 2 diabetes. Along with pharmacological data and in vivo activity studies, this work provides an understanding of how TT-OAD2 can activate GLP-1R and provides insights into the development of orally-administered therapeutic agents for metabolic disorders.

Nature Volume 577 Issue 7790

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