2. Epigenetics
  3. Small Interfering RNA (siRNA)
  4. Givosiran

Givosiran (ALN-AS1) is a small interfering RNA that targets hepatic aminolevulinate synthase 1 (ALAS1) messenger RNA. Givosiran downregulates ALAS1 mRNA and prevents accumulation of neurotoxic δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels. Givosiran demonstrates potent inhibitory activity against ALAS1 in mouse, rat, and cynomolgus monkey models. Givosiran can be used for the research of acute hepatic porphyria (AHP).

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CAS No. : 1639325-43-1

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    Givosiran purchased from MedChemExpress. Usage Cited in: Am J Reprod Immunol. 2024 Aug;92(2):e13916.  [Abstract]

    Heme concentrations in the RL95-2 cells treated by succinate 2.5 mM for 24 h, then the supplement of 5 µM SDHB inhibitor (Fluopyam) or 1 µM ALAS1 inhibitor (Givosiran) for 24 h.

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    Description

    Givosiran (ALN-AS1) is a small interfering RNA that targets hepatic aminolevulinate synthase 1 (ALAS1) messenger RNA. Givosiran downregulates ALAS1 mRNA and prevents accumulation of neurotoxic δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels. Givosiran demonstrates potent inhibitory activity against ALAS1 in mouse, rat, and cynomolgus monkey models. Givosiran can be used for the research of acute hepatic porphyria (AHP)[1][2].

    In Vivo

    Givosiran (10 mg/kg, s.c., single dose) effectively reduces ALAS1 mRNA levels in liver tissue and serum in rats with rapid onset and long-lasting inhibitory properties[2].
    Givosiran (3 mg/kg, s.c., twice weekly for 3 weeks) exhibits complete preventive effect in the rat acute intermittent porphyria (AIP) model[2].
    Givosiran (20 mg/kg, s.c., single dose) works faster and has stronger inhibition than standard Hemoglobin (HY-P2995) treatment in mice[2].
    Givosiran (1-10 mg/kg, s.c., single dose or once daily for 8 weeks) reduces serum and urinary ALAS1 levels in cynomolgus monkey, and repeated administration results in sustained inhibition that is reversible after drug discontinuation[2].

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

    Animal Model: AIP model induced by Phenobarbital established in SD rats[2]
    Dosage: 3 mg/kg
    Administration: Subcutaneous injection (s.c.), twice weekly for 3 weeks
    Result: Completely prevented inducible ALAS1 elevation and associated metabolite accumulation.
    Animal Model: AIP model induced by Phenobarbital established in T1/T2 AIP mice[2]
    Dosage: 20 mg/kg
    Administration: Subcutaneous injection (s.c.), single dose
    Result: Inhibited ALAS1 faster and stronger than Hemoglobin.
    Animal Model: AIP model induced by Phenobarbital established in cynomolgus monkey (M. fascicularis)[2]
    Dosage: 1 and 10 mg/kg (single dose); 5 mg/kg (8 weeks)
    Administration: Subcutaneous injection (s.c.), single dose or once daily for 8 weeks
    Result: Dose-dependently and reversibly inhibited ALAS1 levels and repeated dosing achieved sustained suppression.
    Molecular Weight

    16300.60

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    Sequence

    RNA, (Cm-sp-Am-sp-Gm-Am-Am-Am-(2'-deoxy-2'-fluoro)G-Am-(2'-deoxy-2'-fluoro)G-Um-(2'-deoxy-2'-fluoro)G-Um-(2'-deoxy-2'-fluoro)C-Um-(2'-deoxy-2'-fluoro)C-Am-Um-Cm-Um-Um-Am), 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-oxa13,20,24-triazanonacos-1-yl]-4-hydroxy-2-pyrrolidinyl]methyl hydrogen phosphate], complex with RNA (Um-sp-(2'-deoxy-2'-fluoro)A-sp-(2'-deoxy-2'-fluoro)A-(2'-deoxy-2'-fluoro)G-Am-(2'-deoxy-2'-fluoro)U-Gm-(2'-deoxy-2'-fluoro)A-Gm-(2'-deoxy-2'-fluoro)A-Cm-(2'-deoxy-2'-fluoro)A-Cm-(2'-deoxy-2'-fluoro)U-Cm-(2'-deoxy-2'-fluoro)U-Um-(2'-deoxy-2'-fluoro)U-Cm-(2'-deoxy-2'-fluoro)U-Gm-sp-Gm-sp-Um) (1:1)
    SMILES

    [Givosiran]
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage

    -20°C, sealed storage, away from moisture

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

    Purity & Documentation

    Purity: 96.95%

    SDS (252 KB)

    COA (251 KB) RP-HPLC (219 KB) MS (303 KB)

    Handling Instructions (2242 KB)
    References
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    Givosiran Related Classifications

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    • 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:

    Givosiran1639325-43-1ALN-AS1Small Interfering RNA (siRNA)siRNAaminolevulinateALAS1mRNAδ-aminolevulinicacidporphobilinogenacuteintermittentporphyriaInhibitorinhibitorinhibit

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