Factor D inhibitor 6 is a potent, highly selective and orally active factor D (FD) inhibitor with an IC50 of 30 nM and a Kd of 6 nM. Factor D inhibitor 6 is inactive against factor B, lassical and lectin complement-pathway activation, and a broad assay panel of receptors, ion channels, kinases and proteases[1].
Factor D inhibitor 6 (compound 6) effectively blocks both alternative pathway (AP)-mediated hemolysis in 10% human serum (IC50 = 6 nM) and AP-induced membrane-attack complex (MAC) formation in lepirudinanticoagulated 50% human whole blood (IC50 = 0.14 μM)[1].Factor D inhibitor 6 (compound 6) shows modest inhibition of murine FD (IC50 = 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 IC50 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 EC50 of 0.034 μM[1].
[1]. JÜrgen Maibaum, et al. Small-molecule Factor D Inhibitors Targeting the Alternative Complement Pathway. Nat Chem Biol. 2016 Dec;12(12):1105-1110.