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
Key to terms and symbols Click column headers to sort
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
[1]