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

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

Complement C1s-IN-1 (compound (R)-8) 是一种高选择性 C1s 抑制剂，对人 C1s 的 IC₅₀ 为 36 nM，对小鼠 C1s 为 61 nM，对其他丝氨酸蛋白酶（如 C1r、MASP2、Factor D 等）IC₅₀ 均大于 30,000 nM，显示出极高的选择性。此外，Complement C1s-IN-1 可剂量依赖性抑制人血清诱导的经典补体通路活化（MAC 形成）[1]。

小鼠口服给予 Complement C1s-IN-1（10、30、100 mg/kg）后，血药浓度（Cmax）随剂量升高，从 1032.5 提高至 8895.5 ng/mL，AUC₀–₂₄h 达 139341 ng·h/mL，平均滞留时间 7.66 小时。药物可显著进入脑组织，100 mg/kg 剂量下 2 小时脑浓度为 33559.5 ng/g，脑/血浆比最高达 1.7[1]。