Danicopan CAS# 1903768-17-1

Danicopan (ACH-4471) is a selective small-molecule inhibitor of complement factor D, targeting the alternative pathway of complement activation. In vitro, danicopan potently inhibited human factor D enzymatic activity with an IC₅₀ in the low nanomolar range (~2–10 nM) and suppressed complement-mediated hemolysis in PNH patient-derived erythrocytes, reducing C3 fragment deposition on red blood cells by >80% at concentrations ≥100 nM. In vivo, oral administration in cynomolgus monkeys and humanized mouse models of PNH-like hemolysis demonstrated dose-dependent suppression of alternative pathway activity, decreased C3 opsonization of erythrocytes, and significant preservation of hemoglobin levels; effective plasma concentrations correlated with target engagement, and sustained dosing over several days maintained inhibition of C3-mediated extravascular hemolysis without affecting classical or lectin pathway activity.