Manusiran
Manusiran (Divesiran) is a GalNac-siRNA targeting liver and transmembrane serine protease 6 (Serine protease 6). Manusiran increases hepatic Hepcidin synthesis and plasma levels by silencing TMPRSS6, a negative regulator of hepcidin production, and limits the availability of iron required for erythropoiesis. Combined use of Manusiran with Deferiprone (HY-B0568) reduces ineffective erythropoiesis and hepatic iron overload in a mouse model of β-thalassemia. Manusiran can be used for research on polycythemia vera, type 1 hereditary hemochromatosis, and β-thalassemia.
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- CAS No.: 2646704-10-9
- 화학식: C434H570F19N145O270P40S10
- 분자량:14058.53
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
In Vivo
Single administration of Manusiran (1-3 mg/kg) dose-dependently inhibits hepatic Tmprss6 expression, increases hepcidin levels, normalizes or reduces systemic iron parameters, corrects erythroid parameters, and elevates splenic iron content in Hfe-knockout mice with hereditary hemochromatosis type 1[2].
Single administration of Manusiran (3 mg/kg) or subcutaneous administration of Manusiran (3 mg/kg once every 3 weeks for a total of 6 weeks) potently inhibits hepatic Tmprss6 expression, reduces systemic iron levels, and normalizes erythroid parameters in aged Hfe knockout mice with type 1 hereditary hemochromatosis, with the effects lasting up to 6 weeks; when combined with deferiprone, it further enhances deferiprone-mediated reduction of hepatic iron[2].
Manusiran (3 mg/kg; subcutaneous injection; administered on day 1 and day 14; 2 doses) potently inhibits Tmprss6 expression in the liver of β-thalassemic Hbbth3/+ mice, restores hepcidin levels to normal, reduces serum iron by 70%, improves red blood cell parameters, alleviates ineffective erythropoiesis and splenomegaly, and restores zinc/magnesium homeostasis in the spleen; when combined with deferiprone, its hepatic iron clearance effect is further enhanced[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6N (7-8-week old female, 4 per group)[2]
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Dosage:3 mg/kg
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Administration:s.c.; single injection
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Result:Achieved significant reduction of hepatic Tmprss6 mRNA for at least 3 weeks (P < 0.0001 vs.
PBS control at both 1 and 3 weeks).
Significantly increased hepatic hepcidin mRNA expression.
Increased hepatic mRNA expression of SMAD6 and SMAD7 (BMP/SMAD pathway indicators).
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Animal Model:C57BL/6 background Hbbth3/+ (6-month-old female, β-thalassaemic)[3]
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Dosage:3 mg/kg
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Administration:s.c.; two doses on days 1 and 14
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Result:Significantly reduced liver Tmprss6 mRNA levels, with a two-threefold increase in liver Hamp mRNA (encoding hepcidin) and elevated serum hepcidin levels relative to vehicle controls.
Reduced serum iron levels by 70% relative to vehicle controls.
Increased haemoglobin levels (mean increase of 25 g/dl relative to vehicle), increased red blood cell counts, decreased red cell distribution width, and partially corrected reticulocytosis.
Significantly reduced splenomegaly, with normalisation of splenic architecture (restored white pulp and red pulp regions).
Reduced reactive oxygen species levels in red blood cells to near-normal levels.
When combined with deferiprone, achieved a greater reduction in liver iron levels than either treatment alone, restoring liver iron to normal physiological levels; total spleen iron content did not differ significantly from vehicle controls.
Reduced the proportion of immature erythroid progenitor cells in the spleen (and to a lesser extent in bone marrow), enhancing erythroid maturation and differentiation; combination with deferiprone further increased the percentage of reticulocytes and enucleated erythroid cells in the spleen relative to SLN124 alone.
Normalised elevated splenic zinc and magnesium levels to near-normal levels; liver zinc and magnesium levels remained largely unaffected.
Chemical Information
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CAS No. 2646704-10-9
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분자량 14058.53
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화학식 C434H570F19N145O270P40S10
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SMILES
[Manusiran]
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Synonyms
Divesiran; SLN124
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Sequence
RNA, (Am-sp-(2′-deoxy-2′-fluoro)A-sp-Cm-(2′-deoxy-2′-fluoro)C-Am-(2′-deoxy-2′-fluoro)G-Am-(2′-deoxy-2′-fluoro)A-Gm-(2′-deoxy-2′-fluoro)A-Am-(2′-deoxy-2′-fluoro)G-Cm-(2′-deoxy-2′-fluoro)A-Gm-(2′-deoxy-2′-fluoro)G-Um-sp-(2′-deoxy-2′-fluoro)G-sp-Am), complex with RNA ((2′-deoxy-2′-fluoro)U-Cm-(2′-deoxy-2′-fluoro)A-Cm-(2′-deoxy-2′-fluoro)C-Um-(2′-deoxy-2′-fluoro)G-Cm-(2′-deoxy-2′-fluoro)U-Um-(2′-deoxy-2′-fluoro)C-Um-(2′-deoxy-2′-fluoro)U-Cm-(2′-deoxy-2′-fluoro)U-Gm-(2′-deoxy-2′-fluoro)G-sp-Um-sp-(2′-deoxy-2′-fluoro)U) 5′-[O-[19-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-7,7-bis[12-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-7-mercapto-7-oxido-2,6,8-trioxa-7-phosphadodec-1-yl]-14-mercapto-14-oxido-5,9,13,15-tetraoxa-14-phosphanonadec-1-yl] hydroxy phosphate] (1:1)
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
[2]. Altamura S, et al. SLN124, a GalNAc-siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1. Hemasphere. 2019 Oct 1;3(6):e301. [Content Brief]
[3]. Vadolas J, et al. SLN124, a GalNac-siRNA targeting transmembrane serine protease 6, in combination with deferiprone therapy reduces ineffective erythropoiesis and hepatic iron-overload in a mouse model of β-thalassaemia. Br J Haematol. 2021;194(1):200-210. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Manusiran Related Classifications
HY-147278 Related Classifications
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