YN1548: A novel small-molecule agonist of human glucagon-like peptide-1 receptor for the treatment of type 2 diabetes mellitus and obesity

Sep 13, 2025European journal of pharmacology

YN1548: A new small drug that activates the human GLP-1 receptor to help treat type 2 diabetes and obesity

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Abstract

YN1548 demonstrated a half-maximal effective concentration of 4.59, 24.28, and 2.20 nM for activating the human GLP-1 receptor.

  • YN1548 shows potent binding to the human GLP-1 receptor, activating the cAMP signaling pathway.
  • Maximal efficacy of YN1548 ranged from 101.0% to 103.9%, comparable to the natural GLP-1 (7-36) amide.
  • The compound exhibited biased agonism, favoring cAMP response over β-arrestin recruitment.
  • Pharmacokinetic studies suggest that YN1548 is suitable for oral administration.
  • In diabetic monkeys, oral YN1548 reduced blood glucose levels and enhanced insulin secretion in a concentration-dependent manner.
  • YN1548 also led to reduced food intake and induced weight loss similar to that seen with liraglutide.

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