Iptacopan TFA

Iptacopan (LNP023) TFA is a potent, orally active, and highly selective factor B inhibitor, exhibiting an IC50 of 10 nM and a KD of 7.9 nM. It acts proximally in the complement cascade to prevent red blood cell destruction (hemolysis) in paroxysmal nocturnal hemoglobinuria (PNH) and renal cell damage in IgA nephropathy (IgAN) and C3 glomerulopathy (C3G). Iptacopan TFA is utilized in the study of complement-mediated diseases, particularly PNH, IgAN, and C3G.

Iptacopan (LNP023) TFA demonstrates potent inhibitory effects on the formation of the membrane attack complex (MAC) induced by the alternative complement pathway (AP) in 50% human serum, with an IC50 value of 130 nM. It shows remarkable selectivity over other proteases, with IC50 values of over 30 μM among 41 human proteases, including AP factor D (>100 μM).

Iptacopan (LNP023; 20-180 mg/kg; oral) TFA can prevent arthritis induced by KRN (150 μL) in mice and is effective both prophylactically and therapeutically in a rat membranous nephropathy model. After oral administration of LNP023 TFA (30 mg/kg in rats and 10 mg/kg in dogs), it exhibits a moderate half-life (T 1/2; 3.4 hours in Wistar Han rats and 5.5 hours in Beagle dogs) and C max (410 nM in Wistar Han rats and 2200 nM in Beagle dogs). Following intravenous administration of Iptacopan TFA (1.0 mg/kg in rats and 0.1 mg/kg in dogs), it shows a terminal elimination half-life (T 1/2; 7 hours in Wistar Han rats and 5.6 hours in Beagle dogs).