产品描述
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.

体外活性
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)[3].

体内活性
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[2]. 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)[3].

Cas No.
1646321-63-2

分子式
C25H31ClN2O4

分子量
458.98

别名
Iptacopan HCl;LNP023 hydrochloride

参考文献
[1]Nello Mainolfi, et al. Discovery of 4-((2 S,4 S)-4-Ethoxy-1-((5-methoxy-7-methyl-1 H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases. J Med Chem. 2020 Jun 11;63(11):5697-5722.
[2]Anna Schubart, et al. Small-molecule Factor B Inhibitor for the Treatment of Complement-Mediated Diseases. Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7926-7931.
[3]Dimitrios C Mastellos, et al. Expanding Complement Therapeutics for the Treatment of Paroxysmal Nocturnal Hemoglobinuria. Semin Hematol. 2018 Jul;55(3):167-175.

储存和溶解度
H2O:50 mg/mL (108.94 mM),ultrasonic and warming
DMSO:250 mg/mL (544.69 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years

Note
For research use only .