Inotersen is an antisense oligonucleotide (ASO) therapeutic designed to reduce the production of transthyretin (TTR) protein in the liver. It binds to the messenger RNA encoding transthyretin and promotes its degradation, thereby reducing circulating TTR levels.
Inotersen is used for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adults.
Inotersen is a specialized oligonucleotide-based pharmaceutical ingredient manufactured using controlled chemical synthesis and sophisticated purification technologies. Its quality assessment differs substantially from conventional small-molecule APIs.
Important quality attributes include sequence identity, full-length product content, oligonucleotide purity, truncated sequences, related oligonucleotides, molecular weight, water content, residual solvents, counter-ion composition and biological activity.
CAS Number: 1350653-12-9
Molecular Formula: C230H329N71O122P19S19
Molecular Weight: Approximately 7.0 kDa
Drug Class: Antisense Oligonucleotide
Pharmacological Class: TTR-Directed Antisense Therapeutic
Therapeutic Class: RNA-Targeted Therapy
Therapeutic Area: Neurology / Rare Diseases
Inotersen is designed to bind selectively to the human transthyretin (TTR) mRNA.
After binding to the target RNA, the resulting RNA-DNA hybrid can recruit RNase H1, which cleaves the TTR mRNA. This reduces synthesis of transthyretin protein in the liver.
Reduced TTR production decreases the availability of TTR protein that can form amyloid deposits in tissues, helping address the underlying mechanism of hereditary transthyretin-mediated amyloidosis.
Inotersen is used for:
hATTR amyloidosis is a hereditary disorder in which abnormal transthyretin protein can accumulate as amyloid deposits in multiple tissues, including peripheral nerves.
Inotersen provides a gene-expression-targeted therapeutic approach by reducing TTR protein production rather than directly removing established amyloid deposits.
Inotersen is a chemically modified antisense oligonucleotide incorporating 2'-O-methoxyethyl (2'-MOE) modifications and phosphorothioate linkages. These modifications are designed to improve stability and pharmacological characteristics of the oligonucleotide.
Manufacturing of Inotersen involves specialized oligonucleotide production technologies. Major stages may include:
Inotersen quality evaluation may include:
Inotersen pharmaceutical material should be stored according to validated stability data and applicable product specifications. Appropriate temperature control and protection from unsuitable environmental conditions are important for maintaining oligonucleotide integrity.
Inotersen is relevant to research involving:
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |