FD-IN-1 (Compound 12) is a potent, orally active complement factor D (FD) inhibitor with IC50 of 12 nM.It also inhibits factor XIa (FXIa) and tryptase β2 with IC50 of 7.7 and 6.5 μM, respectively.
in vitro
FD-IN-1 (Compound 12) exhibits functional inhibition of AP activation (IC 50 =0.26 μM) in vitro in a membrane attack complex (MAC) deposition assay using 50% human whole blood (WB).
in vivo
FD-IN-1 (Compound 12) demonstrates systemic suppression of AP activation in a lipopolysaccharide-induced alternative complement pathway (AP) activation model as well as local ocular suppression in intravitreal injection-induced AP activation model in mice expressing human FD. FD-IN-1 (Compound 12) exhibits high oral bioavailability (C57BL6 mice 83%, Beagle dogs 70%) following oral administration (mice and dogs 10 mg/kg). FD -IN-1 (Compound 12) exhibits terminal elimination half-lives (C57BL6 mice 1.6 h and Beagle dogs 3.8 h) following intravenous administration (mice and dogs 1 mg/kg).
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Animal Model:
Human FD knock-in mice
Dosage:
3 and 10 mg/kg
Administration:
Oral gavage
Result:
The AP pathway was fully inhibited for up to 10 h at the 10 mg/kg dose.
