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.
For research use only. We do not sell to patients.
- CAS No.: 1438322-82-7
- Molecular Weight:16121.00
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
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. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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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]
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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)
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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)
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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.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1438322-82-7
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Molecular Weight 16121.00
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SMILES
[Revusiran]
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Synonyms
ALN-TTRSC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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RNA interference technology
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing gene transcription or activating RNA degradation. This mechanism was discovered in plants in 1998 by Andrew Fire and Craig Mello. Today, this phenomenon can be observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals.
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Amyloid: Congo Red Amyloid Staining
Congo red amyloid staining is a histochemical method used to detect extracellular amyloid deposits in tissue sections based on the affinity of Congo red dye for β-pleated sheet-rich protein aggregates. When bound to amyloid, Congo red produces characteristic apple-green birefringence under polarized light microscopy, which is widely regarded as a diagnostic feature of amyloid deposition in histopathology. The diagnostic principle relies on the combination of dye binding (congophilia) and optical anisotropy under polarized illumination, which distinguishes amyloid from most non-amyloid eosinophilic extracellular deposits in routine histological evaluation. Amyloid identification by Congo red staining remains a cornerstone in diagnostic pathology despite the availability of adjunct methods such as immunohistochemistry and mass spectrometry, particularly because of its ability to localize deposits directly within tissue architecture. The specificity of Congo red-positive deposits is incre
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)