Zerlasiran

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Zerlasiran liver targeting subunit
Clinical data
Other namesSLN360
Identifiers
  • N-[(2R,3R,4R,5R,6R)-2-[4-[3-[2,2-bis[3-[4-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxybutoxy-hydroxyphosphinothioyl]oxypropoxymethyl]-3-[6-[[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxy-4-methoxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyhexoxy]propoxy]propoxy-hydroxyphosphinothioyl]oxybutoxy]-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide
UNII
Chemical and physical data
Formula C66H122N6O38P4S4
Molar mass 1859.84 g·mol−1

Zerlasiran is an investigational new drug that is being evaluated to treat atherosclerotic cardiovascular disease. [1] It is small interfering RNA (siRNA) drug candidate designed to reduce levels of lipoprotein(a), a genetically determined cardiovascular risk factor associated with atherosclerotic cardiovascular disease. Developed by Silence Therapeutics, Zerlasiran targets apolipoprotein(a) mRNA in the liver to lower circulating lipoprotein(a) concentrations. The drug is being investigated in early clinical trials as a potential therapeutic option for patients with elevated lipoprotein(a). [1]

Chemistry

Zerlasiran is a double-stranded small interfering RNA (siRNA) of 19 nucleotides in length for strand. Most of the ribonucleotides are chemically modified (mainly 2′-O-methyl or 2′-fluoro-2′-deoxy sugars, with some phosphorothioate linkages) to enhance stability and reduce immunogenicity. The drug is a duplex of these modified oligonucleotides. The sense strand is 5′-conjugated with a tri-antennary N-acetyl-D-galactosamine (GalNAc) cluster attached through a multi-arm phosphodiester linker, enabling targeted delivery to the liver. [2]

Antisense strand: [3]

where:

Sense strand: [3]

where: "[M]" is a triantennary N-acetylgalactosamine (GalNAc) ligand attached to the 5’ end for hepatic targeting. Other abbreviations follow the sense strand modifications as above.

References

  1. 1 2 De Los Reyes C, Rikhi RR, Doherty S, Hernandez S, Mirzai S, Shapiro MD, et al. (December 2025). "Current Clinical Trials for Treating Elevated Lipoprotein(a)". Current Cardiovascular Risk Reports. 19 (1) 7. doi:10.1007/s12170-025-00759-8. PMC   12282488 . PMID   40703143.
  2. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN): Proposed INN: List 129" (PDF). WHO Drug Information. 36 (2). World Health Organization: 533. 2024. Retrieved 30 September 2025.[ dead link ]
  3. 1 2 WO 2023152194,Rider D, Swerdlow D, Campion G, Scrimgeour A, Rambaran C, Wilson R, Machacek M, Schulthess P, Wade J,"Compositions and methods for reducing apolipoprotein(a) expression",published 2023-08-17, assigned to Silence Therapeutics GmbH
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