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Compound class:
Endogenous peptide in human, mouse or rat
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 [6] (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. SARS-CoV-2 and COVID-19: Clinically approved and investigation candidates that target C5 are being evaluated in a number of clinical trials to determine their potential to combat complement-mediated inflammatory tissue damage in the organs of pateints with severe COVID-19.
Species: Human
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Related Sequences  |
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| C5a {Sp: Human} |
TargetsC3a receptor; C5a1 receptor; C5a2 receptor |
| C5a des-Arg {Sp: Human} |
TargetsC5a1 receptor; C5a2 receptor |
| C5a {Sp: Rat} |
TargetsC3a receptor; C5a1 receptor |
