Amustaline (S-303) dihydrochloride, a nucleic acid-targeted alkylator, is an efficient pathogen inactivation agent for blood components containing red blood cells. Amustaline dihydrochloride has three components: an acridine anchor (an intercalator that targets nucleic acids non-covalently), an effector (a bis-alkylator group that reacts with nucleophiles), and a linker (a small flexible carbon chain containing a labile ester bond that hydrolyzes at neutral pH to yield non-reactive breakdown products).

S‐303 (200 μM; 20 h) and glutathione (GSH; 20 mM) inactivates high titres of Chikungunya virus (CHIKV) in red blood cells (RBCs).
S-303 (200 μM; 20 h) and GSH (2 mM) inactivates >6.5 logs of HIV, >5.7 logs of Bluetongue virus, >7.0 logs of Yersinia enterocolitica, 4.2 logs of Serratia marcescens, and 7.5 logs of Staphylococcus epidermidis in whole blood experiments.
S-303 (200 μM; 20 h) and GSH (20 mM) inactivates approximately 5 logs or greater of Y. enterocolitica, E. coli, S. marcescens, S. aureus, HIV, bovine viral diarrhoea virus, bluetongue virus and human adenovirus 5 in RBC.
S-303 (200 μM; 20 h) retains in vitro parameters of RBC function and physiology (including total ATP, extracellular potassium, hemolysis, glucose consumption, lactate production, and pH at 37 °C) compared to conventional RBC.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

S‐303 RBCs (a single transfusion) is well tolerated in rats (50 μmol/kg) and dogs (70 μmol/kg).
S‐303 RBCs (repeated transfusions) is well tolerated in rats (10 μmol/kg) and dogs (10 μmol/kg) with no histopathologic evidence of organ toxicity.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

S‐303 RBCs (a single transfusion) is well tolerated in rats (50 μmol/kg) and dogs (70 μmol/kg).
S‐303 RBCs (repeated transfusions) is well tolerated in rats (10 μmol/kg) and dogs (10 μmol/kg) with no histopathologic evidence of organ toxicity.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Aubry M, et, al. Amustaline (S-303) treatment inactivates high levels of Chikungunya virus in red-blood-cell components. Vox Sang. 2018 Apr;113(3):232-241.  [Content Brief]

  . Mufti NA, et, al. Treatment of whole blood (WB) and red blood cells (RBC) with S-303 inactivates pathogens and retains in vitro quality of stored RBC. Biologicals. 2010 Jan;38(1):14-9.  [Content Brief]

  . North A, et, al. Preclinical pharmacokinetic and toxicology assessment of red blood cells prepared with S-303 pathogen inactivation treatment. Transfusion. 2011 Oct;51(10):2208-18.  [Content Brief]