Zilucoplan（LYS）

Zilucoplan (LYS) is a synthetic macrocyclic peptide inhibitor targeting complement component 5 (C5). Composed of seven non-proteinogenic amino acids, including a lysine residue (LYS), it is engineered to bind C5 and prevent its cleavage into C5a and C5b, thereby blocking the terminal complement pathway. This inhibition reduces complement-mediated inflammation and tissue damage and has shown clinical efficacy in treating autoimmune diseases, notably generalized myasthenia gravis (gMG). Zilucoplan is supplied as a white, lyophilized, amorphous powder with >95% purity and is stable under refrigerated storage.

Appearance

• White to off-white lyophilized powder or solid

• Amorphous, non-crystalline

• Odorless

• Slightly hygroscopic; absorbs moisture from air

Source

• Synthesized by total chemical synthesis (solution-phase or SPPS)

• Non-ribosomal peptide synthesis not applicable (synthetic molecule)

• Available from Ra Pharmaceuticals/UCB (original developers) and custom synthesis vendors (Bachem, Genscript, ProImmune)

Molecular Weight and Structure

• Precise molecular formula and sequence are proprietary

• Molecular weight: ~1500–2000 Da (estimated)

• IUPAC name and SMILES: Not publicly available

• Structure: Macrocyclic peptide containing seven non-proteinogenic amino acids, including lysine

Biological Activity

• Inhibits complement component 5 (C5) cleavage into C5a and C5b

• Blocks terminal complement pathway

• Reduces complement-mediated inflammation and tissue damage

• Demonstrated therapeutic efficacy in generalized myasthenia gravis (gMG)

Purity and Microbial Contamination

• Purity: >95% by HPLC

• Peptide content: Quantified by amino acid analysis or quantitative HPLC

• Water content: <5% by Karl Fischer titration

• Microbial contamination: <100 CFU/g or per mg peptide

• Endotoxin levels: <10 EU/mg peptide

Identity and Quality Control

Shelf Life and Storage

• Store at 2–8°C (refrigerated) or –20°C (frozen)

• Protect from light and moisture

• Shelf life: Typically 2 years from manufacture

• Lyophilized peptides stable for extended periods; avoid repeated freeze-thaw cycles

Applications

• Treatment of generalized myasthenia gravis (gMG)

• Research into complement-mediated and autoimmune diseases

• Development of novel complement inhibitors

• Targeted drug delivery systems

• Potential treatment for other complement-driven diseases

Key Characteristics

• Macrocyclic peptide structure enhances binding affinity and stability

• Specific inhibitor of complement component 5 (C5)

• Potent block of the terminal complement pathway

• Confirmed clinical efficacy in gMG patients

• Synthetic, non-natural peptide with non-proteinogenic amino acids

• Well-defined, though proprietary, chemical structure

• High purity and stability

Citation

• Howard JF Jr, et al. Safety and efficacy of zilucoplan in patients with generalized myasthenia gravis. Lancet Neurol. 2023 Feb;22(2):105-116. PubMed

• Muppidi S, et al. Long-Term Efficacy and Safety of Zilucoplan in gMG: RAISE-XT Study. Neurol Ther. 2024 Mar;13(1):293-311. PubMed

• Patel R, et al. Discovery of Zilucoplan: Macrocyclic Peptide Inhibitor of Complement C5. MDA Virtual Conference 2020.

• FDA Prescribing Information: Zilucoplan (Rystiggo)

• ClinicalTrials.gov: Zilucoplan Trials

• EMA: European Medicines Agency

• UCB Press Releases and Patent Literature related to C5 inhibition and Zilucoplan