Iptacopan (hydrochloride)

1646321-63-2

458.98

DMSO : 200 mg/mL (ultrasonic)

Immunology/Inflammation

LNP023 hydrochloride is an orally bioavailable, highly potent and highly selective factor B inhibitor. LNP023 shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM. LNP023 inhibits factor B with an IC50 value of 10 nM.
IC50 & Target: KD: 7.9 nM (factor B)

IC50: 10 nM (factor B)
In Vitro: LNP023 demonstrates potent inhibition of alternative complement pathway (AP)-induced membrane attack complex (MAC) formation in 50% human serum (IC50 value of 130 nM).

LNP023 exhibits excellent selectivity over other proteases affording IC50 values of >30 uM across a panel of 41 human proteases, including the AP protein factor D (>100 uM).
In Vivo: LNP023 (20-180 mg/kg; oral administration) prevents KRN (150 uL)-induced arthritis in mice and is effective upon prophylactic and therapeutic dosing in an experimental model of membranous nephropathy in rats.

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) following oral administration (rat 30 and, dog 10 mg/kg).

LNP023 exhibits terminal elimination half-lives (T1/2; Wistar Han rats 7 h, beagle dogs 5.6 h) due to high plasma clearance (8, and 2 mL/min/kg respectively combined with large volumes of distribution (2.3, and 0.6 L/kg respectively) following intravenous administration (rat 1.0 and, dog 0.1 mg/kg).