9Y6C

X-ray structure analysis of human Complement Component 5 TE domain in complex with the peptide Ra30303

This is a non-PDB format compatible entry.

Summary for 9Y6C

• Entry DOI: 10.2210/pdb9y6c/pdb
• Related PRD ID: PRD_002585
• Descriptor: Complement C5, peptide Ra30303, GLYCEROL, ... (5 entities in total)
• Functional Keywords: complement, c5, macrocyclic peptide, myasthenia gravis, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 38658.15

Authors

Ye, P.,Hammer, R.P.,Wang, Z.,Dhamnaskar, K.,Hoarty, M.,Ma, Z.,Tang, G.,DeMarco, S.J.,Ricardo, A. (deposition date: 2025-09-08, release date: 2025-12-24)

Primary citation

Ye, P.,Hammer, R.P.,Wang, Z.,Dhamnaskar, K.,Hoarty, M.,Ma, Z.,Tang, G.Q.,DeMarco, S.J.,Ricardo, A.
Discovery of Zilucoplan: A Complement C5 Inhibitor for Treatment of Anti-Acetylcholine Receptor (AChR) Antibody-Positive Generalized Myasthenia Gravis (gMG).
J.Med.Chem., 2025

PubMed Abstract: Complement component 5 (C5) is a protein in the complement cascade and a part of the innate immune system that has been clinically validated as a therapeutic target for several immune-mediated diseases including generalized myasthenia gravis (gMG). In this paper, we discuss the early discovery of zilucoplan, a macrocyclic peptide drug, which was identified via innovative extreme diversity mRNA display (Ma, Z.; Hartman, M. C. T. In Vitro Selection of Unnatural Cyclic Peptide Libraries via mRNA Display. In ; Douthwaite, J. A., Jackson, R. H., Eds.; Springer: New York, 2012; pp 367-390.) against C5 and approved for the treatment of gMG. We highlight the key steps and rationale behind the peptide medicinal chemistry optimization of the initial screening hits, that led to improved potency, stability, and pharmacokinetic properties.

PubMed: 41379101
DOI: 10.1021/acs.jmedchem.5c02537

Experimental method

X-RAY DIFFRACTION (2 Å)