LNP023 hydrochloride is an orally bioavailable, highly potent and highly selective factor B inhibitor with an IC50 of 10 nM. LNP023 shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM.
LNP023 demonstrates excellent selectivity over other proteases affording IC50 values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM).
LNP023 (20-180 mg/kg; oral administration) is effective upon prophylactic and therapeutic dosing in an experimental model of membranous nephropathy in rats and prevents KRN (150 μL)-induced arthritis in mice.
After oral administration (rat 30 and, dog 10 mg/kg), LNP023 exhibits moderate half-lives (T1/2; Wistar Han rats 3.4 h, beagle dogs 5.5 h) and Cmax (Wistar Han rats 410 nM, beagle dogs 2200 nM).