complement C5   

GtoPdb Ligand ID: 8712

Comment: This is the full length, pre-pro-protein structure as represented in NCBI Reference Sequence: NP_001726. This peptide is cleaved into the complement C5 beta chain, complement C5 alpha chain and C5a anaphylatoxin (see the UniProt entry for the human protein P01031).

C5 inhibition is a clinically validated mechanism that is utilised for the control and suppression of complement-induced hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab is a clinically approved anti-C5 monoclonal antibody for PNH. Investigational Phase 1/2 anti-C5 monoclonal RG6101 (SKY59 [4]; IMGT 783) was granted FDA orphan drug designation in September 2017 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Ra Pharmaceuticals is developing a C5 binding synthetic 15-amino-acid macrocyclic peptide (designated research code RA101495; Phase 2) for PNH and other complement-mediated illnesses. RA101495 was granted FDA orphan drug designation for PNH in July 2017. RA101495 binds to a site on C5 distinct from the eculizumab binding site, with the aim of overcoming eculizumab resistance, such as that observed in patients with the Arg885His C5 variant [5] (note that RA101495 is also effective against this variant [4]). It is also designed for subcutaneous self-administration, which would be more convenient for patients, who must be given eculizumab by i.v. infusion by a healthcare professional.
Species: Human
Other ligands which bind to or alter the activity of this ligand
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Ligand Sp. Type Action Value Parameter Concentration range (M) Reference
tesidolumab Hs Antibody Binding 10.9 – 11.7 pKd - 2
pKd 10.9 – 11.7 (Kd 1.2x10-11 – 2x10-12 M) [2]
Description: Binding to full length human C5.
eculizumab Hs Antibody Binding 9.2 – 10.5 pKd - 3,6
pKd 10.5 (Kd 3x10-11 M) [3]
pKd 10.5 (Kd 3x10-11 M) [6]
Description: At pH7.4 in a SPR assay.
pKd 9.2 (Kd 6x10-10 M) [6]
Description: At pH6.0 in a SPR assay.
ravulizumab Hs Antibody Binding 7.7 – 9.3 pKd - 6
pKd 9.3 (Kd 4.9x10-10 M) [6]
Description: At pH7.4 in a SPR assay.
pKd 7.7 (Kd 2.2x10-8 M) [6]
Description: At pH6.0 in a SPR assay.
zilucoplan Hs Inhibitor Binding - - - 1