Zilucoplan

Zilucoplan (RA101495), a 15-amino acid macrocyclic peptide, is a potent complement component 5 (C5) inhibitor. Zilucoplan can be used in research of immune-mediated necrotising myopathy (IMNM)[1][2].

Signaling Pathways >> Immunology/Inflammation >> Complement System

Research Areas >> Inflammation/Immunology

Zilucoplan (RA101495; 1-1000 nM; 30 min) inhibit Lipopolysaccharides-induced increase in C5a plasma levels in human whole blood with an IC50 value of 474.5 pM. Zilucoplan has a 65.7% reduction in C5a plasma levels observed at a concentration of 1 nM[2]. Zilucoplan bins to complement component 5 (C5) and blocks the downstream assembly of the membrane attack complex (MAC; C5b-9) by inhibiting the cleavage of C5 by the C5 convertase into C5a and C5b and binding to preformed C5b to sterically block interaction with C6, thereby inhibiting the formation of membrane pores and subsequent cell death[1].

Zilucoplan (RA101495; 10 mg/kg; S.C.; daily, for 6 d) prevents the development of immune-mediated necrotising myopathy (IMNM) in C5-deficient mice supplemented with human complement[1]. Zilucoplan (10 mg/kg; S.C.; daily, for 6 d) has protection on myopathy prevention in C57BL/6 mice[1]. Animal Model: C57BL/10SnJ C5-deficient (C5def) mice with anti-HMGCR+ IMNM IgG xenografts[1] Dosage: 10 mg/kg Administration: Subcutaneous injection; daily, for 6 days Result: Prevented muscle strength loss in C5def mice with less complement deposition on myofibres and consequently less necrosis/regeneration. Animal Model: C57BL/6 mice with anti-HMGCR+ IMNM IgG xenografts[1] Dosage: 10 mg/kg Administration: Subcutaneous injection; daily, for 6 days Result: Prevented muscle weakness and reduced regenerated myofibres. Decreased necrotic cells as well as regenerating cells expressing foetal myosin.