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<p>In this study, three types of fatty acid side chains were selected to conjugate with different insulin analogue precursors, leading to the design and synthesis of 11 novel insulin analogues. We selected three modifiers to modify the precursor of the insulin analogue. Liquid chromatography-mass spectrometry analysis confirmed that the actual molecular weight of the samples was consistent with the theoretical value. After confirming the structural integrity of the samples, their biological activities were evaluated to verify the necessity and functionality of the modifications. A preliminary assessment was made of the biological activities of all compounds on the HEK293/Luc/INSR cell line, successfully identifying candidate analogue <b>5</b>. Further animal experiments were conducted on analogue <b>5</b>. Through analysis of the body weight, blood drug concentration and AUC of diabetic rats, analogue <b>5</b> exhibited good hypoglycemic activity, effectively prolonging the drug action time and having an ideal application prospect.</p>

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Design, Preparation and Activity Evaluation of Long-Acting Insulin Analogues

  • 期刊论文

  • 发表日期：

    2026年4月20日

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  • Shuchen Pei,
  • Jihong Luo,
  • Shaoyu Cai,
  • Kang Luo,
  • Tianbing Guan,
  • Shan Guan

摘要

In this study, three types of fatty acid side chains were selected to conjugate with different insulin analogue precursors, leading to the design and synthesis of 11 novel insulin analogues. We selected three modifiers to modify the precursor of the insulin analogue. Liquid chromatography-mass spectrometry analysis confirmed that the actual molecular weight of the samples was consistent with the theoretical value. After confirming the structural integrity of the samples, their biological activities were evaluated to verify the necessity and functionality of the modifications. A preliminary assessment was made of the biological activities of all compounds on the HEK293/Luc/INSR cell line, successfully identifying candidate analogue 5. Further animal experiments were conducted on analogue 5. Through analysis of the body weight, blood drug concentration and AUC of diabetic rats, analogue 5 exhibited good hypoglycemic activity, effectively prolonging the drug action time and having an ideal application prospect.