Inclisiran

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Cat Number

API1639324585

CAS Number

1639324-58-5

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Product Detail Description Scientific Support Customer Q&A

CAS Number

1639324-58-5

Storage

Store at -20℃

Synonyms

ALN-PCSsc

Molecular Formula

C529H664F12N176O316P43S6

Molecular Weight

16296.26

Appearance

White to off-white powder

General Description

Inclisiran is a first-in-class, synthetic small-interfering RNA (siRNA) therapeutic. The small molecule has been optimized for stability and hepatocyte uptake. It contains 44 modified nucleotides and terminal phosphorothioate modifications that protect it from nuclease degradation and reduce the potential for immunogenicity. The siRNA is also conjugated to a triantennary N-acetylgalactosamine (GalNAc) ligand, which mediates uptake in the liver through the asialoglycoprotein receptor. Inclisiran's advanced design as an siRNA therapeutic leads to potent and durable action as a PCSK9 inhibitor.

Mechanism of Action

Inclisiran works through a unique RNA interference (RNAi) pathway to reduce LDL-C. It is coupled to a GalNAc ligand which allows it to be specifically delivered to hepatocytes. Inclisiran is subsequently incorporated into the RNA-induced silencing complex (RISC) of liver cells, where it binds to and cleaves PCSK9 messenger RNA (mRNA). Inhibition of PCSK9 mRNA translation prevents the production of PCSK9 proteins. The resulting decrease in PCSK9 levels allows for more rapid recycling of hepatic LDL receptors and a higher clearance of LDL-C from circulation. Chemical modifications to the drug lead to higher stability, liver specificity, and a longer half-life.

Application

Inclisiran is indicated for the reduction of low-density lipoprotein cholesterol (LDL-C) in adults with primary hypercholesterolemia (including heterozygous familial hypercholesterolemia) or mixed dyslipidemia. Inclisiran is used as an adjunct to maximally tolerated statin therapy for patients who require additional LDL-C lowering.

Inclisiran is a novel small-interfering RNA (siRNA) lipid-lowering agent that targets hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) messenger RNA. By conjugating to a GalNAc ligand, the drug is selectively taken up by liver cells, loaded into the RNA-induced silencing complex (RISC), and cleaves PCSK9 mRNA, reducing PCSK9 protein synthesis. Lower PCSK9 increases LDL-receptor recycling and produces sustained ≈50 % reductions in LDL-C which persist for ≥6 months after a single dose.
Pivotal phase III trials enrolling >10 000 patients with heterozygous familial hypercholesterolemia, ASCVD or high-risk equivalents showed consistent 48–52 % placebo-adjusted LDL-C lowering on top of maximally tolerated statin ± ezetimibe, with favourable effects on non-HDL-C, ApoB and Lp(a). Hepatic, renal, muscular and platelet toxicities were not higher than placebo. Compared with monoclonal antibodies, inclisiran offers a longer duration of action, allowing twice-yearly subcutaneous dosing that could improve adherence and lower long-term costs.

Fig. 1 Mechanism of action of Inclisiran. (Zhang Y.; et al. 2023)

References

Zhang Y, et al. Inclisiran: a new generation of lipid-lowering siRNA therapeutic. Frontiers in Pharmacology, 2023, 14: 1260921.

What is the purity of your Inclisiran API?

We supply high-purity Inclisiran API, compliant with current pharmacopeial standards. Specific Certificate of Analysis (CoA) details are available upon request.

What are the recommended storage conditions for Inclisiran?

For long-term stability, Inclisiran should be stored at -20℃.

What is the mechanism of action of Inclisiran?

Inclisiran targets PCSK9 mRNA in hepatocytes via RNA interference, reducing PCSK9 protein synthesis and significantly lowering LDL-C levels.

What is the minimum order quantity (MOQ) for Inclisiran?

Our MOQ for Inclisiran varies. Please contact us with your specific requirements for a customized quote.

How do I request a quote for Inclisiran?

Please contact us via our website or email with your specific quantity and specification requirements for a prompt and competitive quote.