LNP023

LNP023 is a complement factor B (CFB) inhibitor (IC50 = 10 nM). It is selective for CFB over a panel of 41 proteases and 110 other enzymes, receptors, and ion channels (IC50s = >30 µM for all). LNP023 inhibits formation of the membrane attack complex induced by zymosan A (Cay-21175) in isolated human whole blood (IC50 = 150 nM). 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. Formulations containing LNP023 have been used in the treatment of PNH and primary immunoglobulin A nephropathy (IgAN).Formal Name: 4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-piperidinyl]-benzoic acid. CAS Number: 1644670-37-0. Synonyms: Iptacopan. Molecular Formula: C25H30N2O4. Formula Weight: 422.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble: >10 mg/ml, Ethanol: Soluble: >10 mg/ml, PBS (pH 7.2): Sparingly soluble: 1-10 mg/ml. SMILES: CC(C=C1OC)=C(NC=C2)C2=C1CN3[C@@](C4=CC=C(C=C4)C(O)=O)([H])C[C@H](CC3)OCC. InChi Code: InChI=1S/C25H30N2O4/c1-4-31-19-10-12-27(22(14-19)17-5-7-18(8-6-17)25(28)29)15-21-20-9-11-26-24(20)16(2)13-23(21)30-3/h5-9,11,13,19,22,26H,4,10,12,14-15H2,1-3H3,(H,28,29)/t19-,22-/m0/s1. InChi Key: RENRQMCACQEWFC-UGKGYDQZSA-N.