Dulaglutide (revision 3)
Old revision·21:16, 30 Sep 2024·SurvodutideSaff
| Dulaglutide | |
|---|---|
| INN | dulaglutide |
| Class | GLP-1 receptor agonist |
| Architecture | GLP-1 analogue dimer fused to IgG4 Fc |
| Route | Subcutaneous, weekly |
| Compound infobox · conventions | |
Dulaglutide is a GLP-1 receptor agonist constructed as a covalent fusion protein: two modified GLP-1(7–37) analogues joined by a peptide linker to the Fc fragment of a human IgG4 antibody. At about 60 kDa it is an order of magnitude larger than the acylated peptide agonists and is properly a biologic rather than a synthetic peptide.[1]
The fusion strategy extends half-life by two independent mechanisms: the conjugate is far too large for glomerular filtration, and the Fc fragment engages the neonatal Fc receptor, which rescues it from lysosomal degradation and recycles it to the circulation. The resulting half-life of about 90 hours supports weekly dosing.[1]
Architecture and its consequences
[edit]Fusion to Fc is a different engineering philosophy from acylation. Acylation leaves a small peptide with a reversible carrier attachment; fusion produces a permanently large molecule. The trade-offs run in both directions.
In favour of fusion: half-life is long without requiring albumin availability, the molecule is a defined single species rather than an equilibrium between bound and free, and manufacture is by cell culture rather than by solid-phase synthesis, which scales differently.