Solbinsiran
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| Other names | LY3561774; LY-3561774 |
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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]
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年11月07日). "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年11月24日.
- ↑ 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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