GLP-1 ANALOGUE-MODIFIED DIMERS WITH DIFFERENT CONFIGURATIONS, PREPARATION METHOD THEREOF, AND APPLICATION THEREOF IN TREATMENT OF TYPE II DIABETES
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Issued Date -
May 9, 2024
app pub date -
Nov 9, 2020
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Oct 12, 2019
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Abstract
Applications of different configurations of novel glucagon peptide 1 with fatty acid modification or nonmodification in the treatment of T2D or the pancreas protection are provided. The dimer of the present disclosure is formed by two identical cysteine-containing GLP-1 monomers through a disulfide bond. The H-like GLP-1 homodimer (disulfide bond is inside chains) showed remarkable increase in hypoglycemic duration without reducing specific activity. The GLP-1 dimer provided has an in-vivo effective duration of up to 19 days, which significantly prolonged compared with that of the positive control drug Liraglutide with 3 days of effective duration, or thereby greatly promoting the technical advancement in long-acting GLP-1 drugs and facilitating their clinical applications and business. Meanwhile the U-like homodimer (disulfide bond is at the C-terminus) does not affect blood glucose, but can obviously protect pancreatic exocrine cells such as acini and ducts, and improve pancreas function.
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