LNP023
LNP023 性质
| 沸点 | 599.1±50.0 °C(Predicted) |
|---|---|
| 密度 | 1.25±0.1 g/cm3(Predicted) |
| 储存条件 | Store at -20°C |
| 溶解度 | DMSO：50.0（最大浓度 mg/mL）；118.34（最大浓度 mM） |
| 酸度系数(pKa) | 4.07±0.10(Predicted) |
| 形态 | 固体 |
| 颜色 | 米白色至灰色 |
LNP023 用途与合成方法
KD: 7.9 nM (factor B)
IC50: 10 nM (factor B)
Iptacopan (LNP023) demonstrates potent inhibition of alternative complement pathway (AP)-induced membrane attack complex (MAC) formation in 50% human serum (IC
50
value of 130 nM).
Iptacopan (LNP023) exhibits excellent selectivity over other proteases affording IC
50
values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM).
Iptacopan (LNP023; 20-180 mg/kg; oral administration) prevents KRN (150 μL)-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 (T
1/2
; Wistar Han rats 3.4 h, beagle dogs 5.5 h) and C
max
(Wistar Han rats 410 nM, beagle dogs 2200 nM) following oral administration (rat 30 and, dog 10 mg/kg).
Iptacopan exhibits terminal elimination half-lives (T
1/2
; 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).
| Animal Model: | C57BL/6 mice with KRN-induced arthritis |
| Dosage: | 20, 60, and 180 mg/kg |
| Administration: | Orally gavaged; twice a day (b.i.d.) for 14 days |
| Result: | Blocked KRN-induced arthritis. |
