Revusiran sodium (Synonyms: ALN-TTRSC sodium)

Name: Revusiran sodium
Brand: MedChemExpress
SKU: HY-132590A
Rating: 4.5 (0 reviews)

Art. -Nr.: HY-132590A Reinheit: 93.12%: Data Sheet
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Revusiran (ALN-TTRSC) sodium is an RNA interference agent targeting the mRNA of transthyretin (Transthyretin, TTR). Revusiran sodium 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 sodium exhibits favorable nonclinical safety profiles. Revusiran sodium can be used in studies related to transthyretin-mediated amyloidosis.

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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), sodium salt

Revusiran sodium Chemische Struktur

Größe	Verfügbarkeit	Menge
1 mg	Auf Lager	Estimated Time of Arrival: December 31
5 mg	Auf Lager	Estimated Time of Arrival: December 31
10 mg	Angebot einholen
50 mg	Angebot einholen

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Beschreibung

In Vitro

Revusiran sodium 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.

Parmacokinetics

Species	Dose	Route	C_max	AUC_last
Mice^[1]	100 mg/kg	s.c.	29.6 μg/mL	88.9 μg·h/mL
Rat^[1]	30 mg/kg	s.c.	1.21 μg/mL	9.70 μg·h/mL
Monkey^[1]	200 mg/kg	s.c.	33.2 μg/mL	645 μg·h/mL

In Vivo

Revusiran (10-300 mg/kg; subcutaneous injection) sodium 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.

Molekulargewicht

16121 (free acid)

Appearance

Solid

Color

White to off-white

SMILES

[Revusiran (sodium)]

Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Reinheit & Dokumentation

Purity: 93.16%

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Data Sheet (269 KB) SDS (252 KB)

COA (248 KB) LCMS (628 KB)

Handling Instructions (2242 KB)

Verweise

[1]. Sutherland JE, et al. Nonclinical Safety Profile of Revusiran, a 1st-Generation GalNAc-siRNA Conjugate for Treatment of Hereditary Transthyretin-Mediated Amyloidosis. Nucleic Acid Ther. 2020 Feb;30(1):33-49. [Content Brief]

Revusiran sodium Related Classifications

Neurological Disease

Molaritätsrechner
Verdünnungsrechner

Die Formel zur Berechnung von Molaritäten

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass		Concentration		Volume		Molecular Weight *
	=		×		×

The dilution calculator equation

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Diese Gleichung wird häufig abgekürzt als: C₁V₁ = C₂V₂

Concentration _(start)	×	Volume _(start)	=	Concentration _(final)	×	Volume _(final)
	×		=		×
C1		V1		C2		V2

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

RevusiranALN-TTRSCSmall Interfering RNA (siRNA)Transthyretin (TTR)thyroxine-binding prealbuminasialoglycoprotein receptorsRNA interferenceEscherichia coliTTR mRNAhuman peripheral blood lymphocyteshereditary transthyretin-mediated amyloidosishepatocytesGalNAc ligandSalmonella typhimuriumTransthyretinInhibitorinhibitorinhibit

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Revusiran sodium (Synonyms: ALN-TTRSC sodium)

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Revusiran sodium Related Classifications

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