Factor D inhibitor 6 is a potent, highly selective, orally active compound that specifically inhibits the activity of factor D (FD). It demonstrates an IC50 of 30 nM and a Kd of 6 nM. Notably, Factor D inhibitor 6 does not exhibit any inhibitory effects against factor B, classical and lectin complement-pathway activation, nor does it interfere with a broad array of receptors, ion channels, kinases, and proteases.

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

Factor D inhibitor 6 (compound 6) effectively blocks both alternative pathway (AP)-mediated hemolysis in 10% human serum (IC 50 = 6 nM) and AP-induced membrane-attack complex (MAC) formation in lepirudinanticoagulated 50% human whole blood (IC 50 = 0.14 μM)[1]. Factor D inhibitor 6 (compound 6) shows modest inhibition of murine FD (IC 50 = 0.86 μM)[1]. Factor D inhibitor 6 (compound 6) inhibits both hemolysis and component 3 (C3) deposition on the surface of red blood cells (RBCs) with an IC 50 value of 70 nM, consistent with inhibition of the AP amplification loop[1].

Factor D inhibitor 6 (Compound 6; 1-10 mg/kg; Oral gavage; once; C57Bl/6 mice) treatment dosed-ependently inhibits complement activation, with full inhibition at 10 mg/kg. Factor D inhibitor 6 shows sustained inhibition of LPS-induced AP activation for at least 8 h post-dose with an EC 50 of 0.034 μM[1]. Animal Model: C57Bl/6 mice induced by lipopolysaccharide (LPS)[1]Dosage: 1 mg/kg, 3 mg/kg, 10 mg/kg Administration: Oral gavage; once Result: Dosed-ependently inhibited complement activation, with full inhibition at 10 mg/kg.