Factor D inhibitor 6 is a potent, highly selective, and orally active compound that specifically inhibits the activity of factor D (FD) with an IC50 of 30 nM and a Kd of 6 nM. It does not exhibit inhibitory effects against factor B, classical and lectin complement-pathway activation, or a broad array of receptors, ion channels, kinases, and proteases.

FD:30 nM (IC50), FD:6 nM (Kd)

Factor D inhibitor 6 (compound 6) efficiently inhibits the alternative pathway (AP) of complement activation, preventing AP-mediated hemolysis in 10% human serum (IC50 = 6 nM) and formation of the AP-induced membrane-attack complex (MAC) in lepirudin-anticoagulated 50% human whole blood (IC50 = 0.14 μM)[1]. It also shows moderate activity against murine Factor D (FD) with an IC50 of 0.86 μM[1] and effectively blocks hemolysis and deposition of component 3 (C3) on red blood cells (RBCs), indicating inhibition of the AP amplification loop with an IC50 of 70 nM[1].

Administering Factor D Inhibitor 6 (Compound 6; 1-10 mg/kg; via oral gavage; single dose) to C57Bl/6 mice results in a dose-dependent suppression of complement activation, achieving total suppression at a 10 mg/kg dosage. This treatment demonstrates prolonged suppression of LPS-induced alternative pathway (AP) activation for at least 8 hours post-administration, with an effective concentration (EC50) of 0.034 μM. The experiment utilized an animal model of C57Bl/6 mice induced by lipopolysaccharide (LPS), with dosages of 1 mg/kg, 3 mg/kg, and 10 mg/kg administered through oral gavage, leading to dose-dependent inhibition of complement activation, culminating in complete inhibition at 10 mg/kg.