Complement C1s-IN-1 is a potent and selective inhibitor of complement C1s with the advantage of being orally available and brain penetrable, significantly inhibiting human serum-induced formation of membrane attack complexes in a dose-dependent manner and effectively blocking the classical complement pathway

Other serine proteases:>30,000 nM, C1s (human):36 nM, C1s (mouse):61 nM

Complement C1s-IN-1 (compound (R)-8) is a highly selective C1s inhibitor with an IC₅₀ of 36 nM for human C1s and 61 nM for mouse C1s. Complement C1s-IN-1 showed minimal activity against other serine proteases (IC₅₀ > 30,000 nM). Complement C1s-IN-1 also dose-dependently inhibited serum-induced classical complement pathway activation in vitro[1].

Following oral administration in mice (10–100 mg/kg), Complement C1s-IN-1 showed dose-dependent plasma exposure (Cmax up to 8895.5 ng/mL; AUC₀–₂₄h = 139,341 ng·h/mL) with a mean residence time of 7.66 h. Complement C1s-IN-1 exhibited strong brain penetration, with brain concentrations reaching 33,559.5 ng/g at 2 h and a brain/plasma ratio up to 1.7[1].