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
References
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Compositions and methods for antibodies targeting complement protein C5.
Patent number: US8241628 B2. Assignee: Novartis Ag.. Priority date: 05/07/2008. Publication date: 14/07/2012.
3. Evans MJ, Matis L, Mueller EE, Nye SH, Rollins S, Rother RP, Springhorn JP, Squinto SP, Thomas TC, Wang Y et al.. (1995)
Methods and compositions for the treatment of glomerulonephritis and other inflammatory diseases.
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4. Fukuzawa T, Sampei Z, Haraya K, Ruike Y, Shida-Kawazoe M, Shimizu Y, Gan SW, Irie M, Tsuboi Y, Tai H et al.. (2017)
Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases.
Sci Rep, 7 (1): 1080. [PMID:28439081]
5. Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Brodsky AL, Noji H, Kitamura K, Eto T, Takahashi T et al.. (2014)
Genetic variants in C5 and poor response to eculizumab.
N. Engl. J. Med., 370 (7): 632-9. [PMID:24521109]
6. Sheridan D, Yu ZX, Zhang Y, Patel R, Sun F, Lasaro MA, Bouchard K, Andrien B, Marozsan A, Wang Y et al.. (2018)
Design and preclinical characterization of ALXN1210: A novel anti-C5 antibody with extended duration of action.
PLoS ONE, 13 (4): e0195909. [PMID:29649283]