| Chemical Properties | Back Directory | [form ]
Solid | [color ]
Off-white to light yellow | [Sequence]
DNA, d([2′-O-(2-methoxyethyl)]m5rU-sp-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]rG-G-sp-T-sp-T-sp-A-sp-m5C-sp-A-sp-T-sp-G-sp-A-sp-A-sp-[2′-O-(2-methoxyethyl)]rA-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rC-sp-[2′-O-(2-methoxyethyl)]m5rC-sp-[2′-O-(2-methoxyethyl)]m5rC), 5′-[26-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-14,14-bis[[3-[[6-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]hexyl]amino]-3-oxopropoxy]methyl]-8,12,19-trioxo-16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate] |
| Hazard Information | Back Directory | [Uses]
Eplontersen is a triantennary N-acetyl galactosamine (GalNAc3-7a)-conjugated antisense oligonucleotide targeting transthyretin (TTR) mRNA to inhibit production of both variant and wild-type TTR protein. Misfolded TTR induces amyloid fibrils formation in the heart and peripheral nerves, leads to amyloid TTR (ATTR) amyloidosis diseases[1][2][3]. | [in vivo]
Eplontersen (682884) (0.6, 2, 6 mg/kg; s.c.; once a week for 3 weeks) inhibits TTR protein expression in a dose-dependent manner in vivo, without affecting normal growth in transgenic C57BL/6 mice expressing human transthyretin (TTR)[3].
| Animal Model: | Transgenic C57BL/6 mice expressing human transthyretin (TTR) (8-week-old)[3] | | Dosage: | 0.6, 2, 6 mg/kg | | Administration: | Subcutaneous injection; once a week for 3 weeks; performed tail bleeds at various time point; sacrificed mice 72 h following the final administration | | Result: | Decreased TTR mRNA level to 15%, and reduced plasma TTR protein levels to 21% at 6 mg/kg on day 17 after injection.
Showed no significant effect on plasma ALT and AST level, no inhibition on body weight, organ weight, spleen weight, and kidney weight as well. |
| [References]
[1] Aimo A, et al. RNA-targeting and gene editing therapies for transthyretin amyloidosis. Nat Rev Cardiol. 2022 Mar 23. DOI:10.1038/s41569-022-00683-z
[2] Diep JK, et al. Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Br J Clin Pharmacol. 2022 Jul 22. DOI:10.1111/bcp.15468
[3] Prakash Thazha P, et al. Antisense oligonucleotides to hepatitis B virus RNA or transthyretin mRNA conjugated with N-acetylgalactosamine targeting moieties: World Intellectual Property Organization, WO2014179627[P]. 2014-11-06. |
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