Peginesatide API is a synthetic, PEGylated peptide-based erythropoiesis-stimulating agent (ESA). Unlike recombinant erythropoietins, peginesatide does not have amino-acid sequence homology with erythropoietin. It consists of two identical 21-amino-acid peptide chains connected through a linker and covalently attached to a branched PEG moiety. The peptide portion is approximately 4.9 kDa, while the PEG portion is approximately 40 kDa, giving the complete molecule an approximate molecular weight of 45 kDa.
Peginesatide is also known as Hematide, AF-37702 and AF37702. The active-moiety CAS Registry Number is 913976-27-9. The marketed pharmaceutical substance is peginesatide acetate, for which a separate CAS number, 1185870-58-9, is recorded in FDA/GSRS-derived data.
Peginesatide activates the human erythropoietin receptor and stimulates erythropoiesis. It was developed for the treatment of anemia associated with chronic kidney disease in adult patients receiving dialysis.
Peginesatide is a synthetic, non-recombinant, PEGylated dimeric peptide. The molecule contains two identical peptide chains, each consisting of 21 amino acids, covalently connected by a linker derived from iminodiacetic acid and β-alanine. A lysine-branched bis-(methoxypolyethylene glycol) chain of approximately 40 kDa is attached to the peptide structure.
The reported empirical formula for the free-base form is:
C₂₀₃₁H₃₉₅₀N₆₂O₉₅₈S₆
with a total molecular weight of approximately 45,000 Da. Because the PEG component is polymeric, molecular weight is appropriately expressed as an approximate/average value rather than as a conventional small-molecule molecular weight.
Manufacturing peginesatide requires specialized peptide synthesis, controlled PEG conjugation, purification and analytical characterization. Because it is a PEGylated peptide rather than a conventional small-molecule API, quality evaluation should include orthogonal methods appropriate for peptide-PEG conjugates.
Regulatory documentation for peginesatide describes controls including RP-HPLC, SEC, HPLC content, ELISA biological potency, HPLC impurities, sulfoxidation and degradation products, together with physical-chemical and microbiological controls for the finished pharmaceutical product.
For an API manufacturer, important quality attributes include molecular identity, peptide integrity, PEGylation/conjugation, purity, related substances, degradation products, aggregation and biological activity.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| pH (1% Solution) | 4.0 – 6.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |