Amustaline (S-303) dihydrochloride is a nucleic acid-targeted alkylator recognized for its efficacy as a pathogen inactivation agent in blood components containing red blood cells. This compound comprises three key elements: an acridine anchor (a non-covalently bonding intercalator targeting nucleic acids), an effector (a bis-alkylator group that interacts with nucleophiles), and a linker (a flexible carbon chain with a labile ester bond, hydrolyzing at neutral pH to non-reactive products).

S‐303 (200 μM; 20 h) and glutathione (GSH; 20 mM) inactivates high titres of Chikungunya virus (CHIKV) in red blood cells (RBCs)[1]. 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[2]. 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[2]. 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[2].

S‐303 RBCs (a single transfusion) is well tolerated in rats (50 μmol/kg) and dogs (70 μmol/kg)[3]. 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[3].