Manusiran  (Synonyms: Divesiran; SLN124)

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^[1][2][3].

Manusiran (3 mg/kg; subcutaneous injection; single dose) potently inhibits hepatic Tmprss6 expression for at least 3 weeks and increases hepcidin levels in healthy C57BL/6N mice^[2].
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 Hbb^th3/+ 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.

14058.53

C₄₃₄H₅₇₀F₁₉N₁₄₅O₂₇₀P₄₀S₁₀

2646704-10-9

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)

[Manusiran]

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Kremyanskaya M, et al. Initial Results from a Phase 1/2 Study Evaluating Divesiran, a Novel Galnac Conjugated siRNA, in Patients with Polycythemia Vera (SANRECO)[J]. Blood, 2024, 144: 656.

  [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]