Oral Small-Molecule GLP-1 Receptor Agonists: Lessons from Clinical Candidates and a Blueprint for Next-Generation Design. (PubMed, J Med Chem) - Oct 28, 2026 - "The recent clinical advancement of oral, nonpeptidic GLP-1 RAs, including danuglipron, lotiglipron, DA-302168S, and orforglipron, the first approved oral small-molecule GLP-1 RA, demonstrates that the peptide-only barrier can be overcome. We also discuss practical considerations for screening cascades, selection of preclinical species and models, formulation optimization and prospective safety assessment. Collectively, these insights provide a conceptual framework for the rational design of oral small-molecule GLP-1RAs, with broader implications for developing therapies challenging G protein-coupled receptor (GPCR) targets."
Journal • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus
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Bingxing Zhang; Boxin Zhang; Changhua Ke; Chao Tang; Chengyuan Liang; Hong Gao; Jinrong Hu; Juan Xia; Lei Tian; Mengzhou Wang; Qianqian Zhao; Yunfei Zhang
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