LNP023 (hydrochloride)

LNP023 is a complement factor B (CFB) inhibitor (IC₅₀ = 10 nM).¹ It is selective for CFB over a panel of 41 proteases and 110 other enzymes, receptors, and ion channels (IC₅₀s = >30 µM for all).² LNP023 inhibits formation of the membrane attack complex induced by zymosan A (Item No. 21175) in isolated human whole blood (IC₅₀ = 150 nM).¹ It blocks hemolysis of erythrocytes isolated from patients with paroxysmal nocturnal hemoglobinuria (PNH; IC₅₀ = 400 nM), a disease characterized by immune-mediated red blood cell destruction, anemia, and blood clots. LNP023 (60 mg/kg twice per day) reduces levels of the alternative pathway cleavage products complement factor Ba, -C3d, and -C5a in the joints, levels of inflammatory cell infiltrates in joint tissues, and arthritis disease severity in a K/BxN serum transfer-induced mouse model of inflammatory arthritis. It also decreases proteinuria and serum levels of urea and creatinine and prevents hair loss and kidney damage in an MRL-lpr mouse model of lupus nephritis when administered at a dose of 30 mg/kg per day.³ Formulations containing LNP023 have been used in the treatment of PNH and primary immunoglobulin A nephropathy (IgAN).

WARNING This product is not for human or veterinary use.

1. Schubart, A., Anderson, K., Mainolfi, N., et al. Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proc. Natl. Acad. Sci. USA 116(16), 7926-7931 (2019).

2. Mainolfi, N., Ehara, T., Karki, R.G., et al. Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-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. 63(11), 5697-5722 (2020).

3. Chen, K., Deng, Y., Shang, S., et al. Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice. Biomed. Pharmacother. 153:113433, (2022).