Inclisiran is a small interfering RNA (siRNA)-based therapeutic designed to reduce low-density lipoprotein cholesterol (LDL-C). It is a first-in-class PCSK9-targeting RNA interference medicine that works primarily in hepatocytes to reduce production of proprotein convertase subtilisin/kexin type 9 (PCSK9).
Inclisiran is used as an adjunct to diet and other lipid-lowering therapies for the treatment of adults with primary hypercholesterolemia or mixed dyslipidemia, according to applicable regulatory approvals.
Inclisiran is a specialized oligonucleotide-based pharmaceutical active ingredient requiring controlled chemical synthesis, purification and extensive analytical characterization. Unlike conventional small-molecule APIs, its quality assessment requires sequence-specific and molecular characterization.
Important quality attributes may include identity, sequence integrity, purity, truncated oligonucleotide impurities, related substances, molecular weight, water content, residual solvents, counter-ion content and biological activity.
CAS Number: 1637597-42-6
Molecular Formula: C645H1080F3N179O221P43S6
Molecular Weight: Approximately 17.3 kDa
Drug Class: PCSK9 Inhibitor
Pharmacological Class: Small Interfering RNA (siRNA) Therapeutic
Therapeutic Class: Lipid-Lowering Agent
Therapeutic Area: Cardiovascular / Metabolic Disorders
Inclisiran uses RNA interference (RNAi) to reduce hepatic production of PCSK9.
After uptake by hepatocytes, the active siRNA strand associates with the RNA-induced silencing complex (RISC). The complex recognizes complementary PCSK9 messenger RNA (mRNA), resulting in its degradation and reduced synthesis of PCSK9 protein.
Lower intracellular PCSK9 levels increase the availability of LDL receptors on hepatocyte surfaces. This enhances hepatic uptake and clearance of circulating LDL-C, resulting in sustained reduction of LDL cholesterol.
Inclisiran is used in pharmaceutical treatment approaches involving:
The precise approved indication and use in combination with other lipid-lowering therapies depend on regional regulatory labeling.
Inclisiran represents an important application of RNA interference technology in cardiovascular medicine. Rather than directly inhibiting circulating PCSK9 protein, it reduces PCSK9 production at the mRNA level inside hepatocytes.
Its long-lasting pharmacological effect allows infrequent dosing, which is a notable characteristic of the therapeutic platform.
Inclisiran incorporates a triantennary N-acetylgalactosamine (GalNAc) ligand that facilitates targeted uptake into hepatocytes through the asialoglycoprotein receptor.
This targeted delivery approach enables the siRNA to reach liver cells efficiently while supporting prolonged PCSK9 suppression.
Inclisiran is a chemically synthesized, double-stranded siRNA conjugate. Its manufacturing requires specialized oligonucleotide synthesis, purification and characterization technologies.
Key manufacturing considerations include:
Inclisiran quality evaluation may include:
Inclisiran-containing 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 the integrity of the siRNA-based therapeutic.
Inclisiran is relevant to research involving:
Inclisiran is a PCSK9-targeting siRNA therapeutic with CAS Number 1637597-42-6 and an approximate molecular weight of 17.3 kDa. It reduces hepatic PCSK9 production through RNA interference, increasing LDL receptor activity and enhancing clearance of LDL cholesterol from the bloodstream.
| 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% |