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Solbinsiran, is a GalNAc conjugated small interfering RNA (siRNA) therapy, that targets angiopoietin-like 3. It is developed by Eli Lilly and Company to reduce the level of apolipoprotein B and reduce the risk of cardiovascular disease.[1][2][3]
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| Other names | LY3561774; LY-3561774 |
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Mechanism of action edit
Solbinsiran is a GalNAc-conjugated Dicer-substrate siRNA (DsiRNA) that targets ANGPTL3 expression in the liver. ANGPTL3 plays a role in regulating lipid metabolism, and by inhibiting its expression, Solbinsiran aims to lower lipid levels, particularly triglycerides and low-density lipoprotein cholesterol (LDL-C) (Triglyceride Forum).
Preclinical and Clinical Research edit
In preclinical studies, Solbinsiran demonstrated significant reductions in human ANGPTL3 mRNA expression in hepatocytes and a substantial reduction in circulating ANGPTL3 protein levels in cynomolgus monkeys (Triglyceride Forum). In Phase 1 studies, it showed potential as a therapeutic option for reducing ANGPTL3 levels and triglycerides (TG) in patients with dyslipidemia (Triglyceride Forum).
Clinical applications edit
The therapy is currently investigational and has undergone testing in clinical settings for cardiovascular diseases.
References edit
- ^ Dudek, Hank; Abrams, Marc; Saxena, Utsav; Turanov, Anton; Brown, Bob; Ruotolo, Giacomo; Michael, Laura (2023-11-07). "Abstract 12705: Identification and Characterization of Solbinsiran, a GalNAc Conjugated siRNA Targeting Angiopoietin-Like 3". Circulation. 148. Hagerstown, MD: Lippincott Williams & Wilkins. doi:10.1161/circ.148.suppl_1.12705. S2CID 266405164. Retrieved 2023-11-24.
- ^ Biessen, Erik A.L.; Van Berkel, Theo J.C. (December 2021). "N-Acetyl Galactosamine Targeting: Paving the Way for Clinical Application of Nucleotide Medicines in Cardiovascular Diseases". Arteriosclerosis, Thrombosis, and Vascular Biology. 41 (12): 2855–2865. doi:10.1161/ATVBAHA.121.316290. PMID 34645280.
- ^ Carugo, S.; Sirtori, C. R.; Gelpi, G.; Corsini, A.; Tokgozoglu, L.; Ruscica, M. (November 2023). "Updates in Small Interfering RNA for the Treatment of Dyslipidemias". Current Atherosclerosis Reports. 25 (11): 805–817. doi:10.1007/s11883-023-01156-5. PMC 10618314. PMID 37792132.
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