Mipomersen is a synthetic antisense oligonucleotide active pharmaceutical ingredient designed to target human apolipoprotein B-100 (apoB-100) messenger RNA. Mipomersen sodium is a 20-nucleotide phosphorothioate oligonucleotide containing 2′-O-methoxyethyl modifications and is associated with inhibition of apoB-100 protein synthesis.
Mipomersen sodium has the molecular formula C₂₃₀H₃₀₅N₆₇Na₁₉O₁₂₂P₁₉S₁₉ and a molecular weight of 7,594.9 g/mol. The sodium salt is identified by CAS Number 629167-92-6.
Mipomersen works through an antisense mechanism directed against apoB-100 mRNA. The oligonucleotide binds to its complementary mRNA sequence, resulting in RNase H-mediated degradation of the target mRNA and reduced translation of apoB-100. ApoB-100 is the principal apolipoprotein associated with LDL and its metabolic precursor VLDL.
Mipomersen sodium is a chemically synthesized phosphorothioate oligonucleotide. Its structure incorporates modified nucleosides, including 2′-O-methoxyethyl nucleosides, and methyl-modified cytosine and uracil bases.
Mipomersen is an antisense oligonucleotide developed to reduce production of apolipoprotein B-100 by targeting its messenger RNA. By reducing apoB-100 synthesis, mipomersen affects the production and metabolism of apoB-containing lipoproteins.
Mipomersen sodium was marketed as Kynamro and was developed for use in patients with homozygous familial hypercholesterolemia. Its regulatory status and commercial availability can vary by market and should be evaluated according to applicable regional requirements.
Mipomersen binds specifically to the coding region of human apoB-100 mRNA through Watson-Crick base pairing. The resulting RNA-DNA hybrid is recognized by RNase H, which promotes degradation of the target mRNA and consequently inhibits translation of apoB-100 protein.
Because Mipomersen is a large antisense oligonucleotide rather than a conventional small-molecule API, its quality characterization requires analytical approaches appropriate for oligonucleotide drug substances.
Relevant quality attributes can include identity, sequence-related characterization, purity, oligonucleotide-related impurities, residual solvents/reagents, water content, counter-ion/sodium content and other product-specific quality attributes.
The exact acceptance criteria should be established according to the applicable validated analytical methods and approved API specification.
Mipomersen sodium should be stored and handled according to the applicable approved specification, stability data and safety documentation. Appropriate controls should be used to minimize exposure to conditions that may affect oligonucleotide quality and stability.
Specific commercial storage requirements should be confirmed against the applicable product/API documentation.
Mipomersen API should be packaged using a suitable pharmaceutical-grade container system designed to protect the oligonucleotide material from contamination and environmental exposure.
Packaging configuration and available quantities should be confirmed according to customer and project requirements.
Mipomersen is a specialized antisense oligonucleotide API with a defined sequence-based structure and a molecular weight of approximately 7.6 kDa. Its unique oligonucleotide chemistry requires appropriate analytical characterization and quality controls throughout pharmaceutical development and manufacturing.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Loss on Drying | NMT 5.0% |
| Residue on Ignition | NMT 5.0% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | pH (1% Solution) |
| Individual Impurity | NMT 2.0% |
| Total Impurities | NMT 5.0% |
| Water Content | NMT 5.0% |