2. Epigenetics Neuronal Signaling
  3. Small Interfering RNA (siRNA) Transthyretin (TTR)
  4. Revusiran

Revusiran (ALN-TTRSC) is an RNA interference agent targeting the mRNA of transthyretin (Transthyretin, TTR). Revusiran mediates sequence-specific degradation of TTR mRNA through RNA interference, reduces the synthesis of TTR protein, binds to GalNAc ligands, and is taken up by hepatocytes via the asialoglycoprotein receptor. Revusiran exhibits favorable nonclinical safety profiles. Revusiran can be used in studies related to transthyretin-mediated amyloidosis.

The free form of the compound is prone to instability, it is advisable to consider the stable salt form (Revusiran sodium) that retains the same biological activity.

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RNA, ((2′-deoxy-2′-fluoro)U-Gm-(2′-deoxy-2′-fluoro)G-Gm-(2′-deoxy-2′-fluoro)A-Um-(2′-deoxy-2′-fluoro)U-Um-(2′-deoxy-2′-fluoro)C-(2′-deoxy-2′-fluoro)A-(2′-deoxy-2′-fluoro)U-Gm-(2′-deoxy-2′-fluoro)U-Am-Am-Cm-(2′-deoxy-2′-fluoro)C-Am-(2′-deoxy-2′-fluoro)A-Gm-(2′-deoxy-2′-fluoro)A), 3′-[[(2S,4R)-1-[29-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-14,14-bis[[3-[[3-[[5-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-1-oxopentyl]amino]propyl]amino]-3-oxopropoxy]methyl]-1,12,19,25-tetraoxo-16-oxa-13,20,24-triazanonacos-1-yl]-4-hydroxy-2-pyrrolidinyl]methyl hydrogen phosphate], complex with RNA (Um-(2′-deoxy-2′-fluoro)C-Um-(2′-deoxy-2′-fluoro)U-Gm-(2′-deoxy-2′-fluoro)G-(2′-deoxy-2′-fluoro)U-(2′-deoxy-2′-fluoro)U-Am-(2′-deoxy-2′-fluoro)C-Am-Um-Gm-(2′-deoxy-2′-fluoro)A-Am-(2′-deoxy-2′-fluoro)A-Um-(2′-deoxy-2′-fluoro)C-Cm-(2′-deoxy-2′-fluoro)C-Am-sp-(2′-deoxy-2′-fluoro)U-sp-Cm) (1:1)

Revusiran 構造式

CAS 番号 : 1438322-82-7

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Revusiran 関連抗体

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製品説明

Revusiran (ALN-TTRSC) is an RNA interference agent targeting the mRNA of transthyretin (Transthyretin, TTR). Revusiran mediates sequence-specific degradation of TTR mRNA through RNA interference, reduces the synthesis of TTR protein, binds to GalNAc ligands, and is taken up by hepatocytes via the asialoglycoprotein receptor. Revusiran exhibits favorable nonclinical safety profiles. Revusiran can be used in studies related to transthyretin-mediated amyloidosis[1].

体外実験

Revusiran shows no mutagenicity at concentrations up to 5000 μg/plate, with or without a metabolic activation system, in bacterial reverse mutation assays using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Revusiran 関連抗体
体内実験

Revusiran (10-300 mg/kg; subcutaneous injection) is well tolerated in cynomolgus monkeys, mice and rats[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Cynomolgus monkeys (2-3 years old; sexually mature 5-6 years old for 39-week study; male for safety pharmacology and acute toxicity)[1]
Dosage: 10 mg/kg, 30 mg/kg, 100 mg/kg (Safety pharmacology); 300 mg/kg (Acute toxicity); 30 mg/kg, 100 mg/kg, 300 mg/kg (6-week repeat-dose); 15 mg/kg, 75 mg/kg, 200 mg/kg (39-week repeat-dose)
Administration: s.c. (single doses on separate days, Safety pharmacology); s.c. (single dose, Acute toxicity); s.c. (5 consecutive daily doses then 5 weekly doses, 6-week repeat-dose); s.c. (5 consecutive daily doses then 39 weekly doses, 39-week repeat-dose)
Result: Showed no effects on cardiovascular or respiratory function at doses up to 100 mg/kg; no neurological abnormalities in repeat-dose studies at doses up to 300 mg/kg.
Reduced serum TTR by 80% relative to baseline on day 8 and 90% on day 15 at 300 mg/kg acute dose; no changes in complement split products or plasma cytokines.
Reduced serum TTR by ≥95% from baseline by day 15, maintained throughout dosing, with partial recovery at 30 and 100 mg/kg, or sustained reduction at 300 mg/kg post-recovery in 6-week repeat-dose studies; reduced vitamin A by 88%-93% from baseline, and thyroxine by 26%-50% from baseline at end of dosing, with partial/full recovery post-recovery; caused reversible elevations in ALP and minimal, partially recoverable microscopic findings at ≥100 mg/kg.
Reduced serum TTR by ≤98% from baseline, vitamin A by ≤95% from baseline, and thyroxine by ≤36% from baseline, with full recovery post-recovery in 39-week repeat-dose studies; caused reversible elevations in ALP, 27% reduction in mean body weight in high-dose males, and full/partially recoverable microscopic/ultrastructural findings at ≥15 mg/kg; no mitochondrial changes observed.
臨床実験
分子量

16121.00

CAS 番号
SMILES

[Revusiran]
輸送条件

Room temperature in continental US; may vary elsewhere.
保管条件

Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
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Keywords:

Revusiran1438322-82-7ALN-TTRSCSmall Interfering RNA (siRNA)Transthyretin (TTR)thyroxine-binding prealbuminsiRNAtransthyretinamyloidosisGalNAcN-acetylgalactosamineInhibitorinhibitorinhibit

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