Reactome | C5 binds C5 inhibitors

C5 binds C5 inhibitors

Stable Identifier

R-HSA-9691621

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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Activation of the complement system significantly contributes to the pathogenesis of numerous acute and chronic diseases. Monoclonal antibodies (mAbs) that recognize the human complement protein C5 have been shown to effectively block C5 cleavage, thereby preventing the generation of pro-inflammatory complement components (Thomas et al. 1996, review Horiuchi & Tsukamoto 2016). The mAb eculizumab was the first therapeutic for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (Rother et al. 2007). Ravulizumab, also used to treat PNH, was engineered from eculizumab to have an inherently longer circulating half-life so as to extend dosing intervals (Sheridan et al. 2018). Tesidolumab is an investigational mAb targeting complement C5, inhibiting terminal complement activation. Zilucoplan is a small macrocyclic peptide that binds to C5 with high affinity and specificity. It is being investigated for the treatment of myasthenia gravis (MG), a rare autoimmune disease (Howard et al. 2020).

Literature References

PubMed ID	Title	Journal	Year
17989688	Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria Rollins, SA, Brodsky, RA, Bell, L, Rother, RP, Mojcik, CF	Nat. Biotechnol.	2007
9171898	Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv Matis, LA, Thomas, TC, Squinto, SP, Evans, MJ, Nye, SH, Hartman, SL, Giannoni, MA, Rollins, SA, Elliott, EA, Rother, RP	Mol. Immunol.	1996
29649283	Design and preclinical characterization of ALXN1210: A novel anti-C5 antibody with extended duration of action Andrien, B, Marozsan, A, Sun, F, Wang, Y, Lasaro, MA, Zhang, Y, Sheridan, D, Patel, R, Yu, ZX, Bouchard, K, Tamburini, P	PLoS ONE	2018
32065623	Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial Henegar, R, Lam, L, Pulley, M, Zakalik, K, Small, G, Vu, T, Dimachkie, M, Colgan, S, Bromberg, M, Bertorini, T, David, W, Bratton, J, Shabbir, Y, Freimer, M, Elsheikh, B, Kaminski, HJ, Kaminski, HJ, Sivak, M, Farmakidis, C, Fetter, M, Pasnoor, M, Barnett, D, Mozaffar, T, Wolfe, GI, Wolfe, GI, Pillai, R, Vu, TH, MacDougall, JE, Lange, D, Hewitt, W, Holzberg, S, Habib, AA, Benatar, MG, Liu, T, Bernitsas, E, Hoarty, M, Matisak, P, MacDougall, J, Genge, A, Siddiqi, Z, Silvestri, N, Gibson, S, Freimer, ML, Zilucoplan MG Study Group, -, Zilucoplan MG Study Group, -, Patterson, K, Sharma, A, Bayat, E, Hinton, JL, Hinton, JL, Olapo, T, Khan, S, Nicolle, M, Lisak, RP, Kohli, A, Barohn, R, Harvey, B, Sachdev, A, Sullivan, P, Nye, J, Pontius, A, Patrick, K, Farzaneh-Far, R, Farzaneh-Far, R, Malik, R, Benatar, M, Mathew, V, Ho, D, Chopra, M, Sershon, LM, Lewis-Collins, TD, Howard, JF, Howard, JF, Khatri, B, Aly, R, Abu-Rub, M, Duda, PW, Duda, PW, Guidon, A, Roy, B, Nowak, RJ, Nowak, RJ, Traub, RE, Berger, A, Jia, K, Lindman, E, Janecki, T	JAMA Neurol	2020