Structure Analysis of Tirzepatide: Pharmacodynamic Mechanism and Key Intermediates
Publish Time:
2025-08-22
Tirzepatide, as a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has become an important drug in the field of metabolic disease treatment due to its synergistic metabolic regulation and convenient once-weekly subcutaneous injection administration. High-quality intermediates and efficient peptide synthesis technology are the core supports to ensure the production of this drug.
The function of Tirzepatide
The structure and pharmacodynamics of Tirzepatide
Tirzepatide is a linear peptide containing 39 amino acids, optimized based on the natural GIP structure, similar in size to GIP and GLP-1. The initial amino acid sequence of Tirzepatide is the human GIP sequence, retaining 9 homologous amino acids from GIP and 10 amino acids common to both GIP and GLP-1, achieving dual receptor agonism and long-acting effects through multi-site structural modifications.
C20 contains a fatty diacid structure, connected to a lysine residue via a linker, promoting binding to albumin and extending the half-life. Position 2 contains an α-amino isobutyric acid (Aib) residue, which occupies the dipeptidyl peptidase-4 (DPP-4) binding site, preventing hydrolysis by DPP-4. The 10 amino-terminal amino acids are the same as those in the exenatide amino acid series. *
The structure of Tirzepatide
Tirzepatide intermediates
In the preparation process of Tirzepatide, the synthesis of intermediates, side chains, and fragments is crucial and is the key to ensuring efficient and stable drug production.
Tongjun Pharmaceuticals is committed to providing sustainable and affordable peptides, supplying side chains Key hydrophilic linkers in the AEEA series intermediates: AEEA, AEEA-AEEA, Fmoc-AEEA-OH, produced using a self-developed process different from existing technologies, free of β-alanine impurities, with high purity and stable quality;
Using EMPHASES ® Peptide fragments (≥8 amino acids) produced by the new liquid-phase peptide synthesis platform, with purity greater than 95%;
The four fragments of the original process have completed small-scale and pilot-scale verification, and fragments different from the original process can be customized as required, suitable for Tirzepatide process development and optimization.
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*Zhang Yanping, Huang Bin, Lu Jinmiao, et al. The first GIP/GLP-1 dual receptor agonist: Tirzepatide [J]. Chinese Journal of Clinical Pharmacy, 2025, 34(07):533-539. DOI:10.19577/j.1007-4406.2025.07.011.
