Opportunities for new therapies based on the natural regulators of complement activation - PubMed (original) (raw)
Review
Opportunities for new therapies based on the natural regulators of complement activation
Eve Brook et al. Ann N Y Acad Sci. 2005 Nov.
Abstract
While the complement system is an essential component of immunity, shutting down all or part of it could be beneficial in a wide range of clinical situations. Designer, small-molecule, protease inhibitors and antagonists of protein-protein interactions are under development, while an approach based on a humanized monoclonal antibody to the C5 component works effectively against the later stages of complement activation and is close to completing clinical trials. The cobra venom factor depletes plasma of essential complement components, and a humanized (nonimmunogenic) version is being sought. Perhaps the most promising approach to comprehensive complement downregulation, however, is the exploitation of innate regulators of complement activation, with two products in clinical trials. The potential for more efficacious complement blockers of this kind is growing because of better targeting, but a deeper knowledge at the atomic level of mechanisms of action of these regulators is needed to underpin a rational approach to design of still more potent complement inhibitors.
Similar articles
- [A new low molecular-weight protein effector of human complement from the venom of the Central Asian cobra Naja naja oxiana].
Kozlov LV, Soliakov LS, Zinchenko AA. Kozlov LV, et al. Bioorg Khim. 1984 Mar;10(3):323-32. Bioorg Khim. 1984. PMID: 6567467 Russian. - Statin drugs do not affect serum complement activation in vitro.
Lappegård KT, Hvassing T, Mollnes TE. Lappegård KT, et al. Scand J Immunol. 2004 Jul-Aug;60(1-2):178-83. doi: 10.1111/j.0300-9475.2004.01439.x. Scand J Immunol. 2004. PMID: 15238087 - A computational model for the evaluation of complement system regulation under homeostasis, disease, and drug intervention.
Zewde N, Morikis D. Zewde N, et al. PLoS One. 2018 Jun 6;13(6):e0198644. doi: 10.1371/journal.pone.0198644. eCollection 2018. PLoS One. 2018. PMID: 29874282 Free PMC article. - Synthesis of antibody conjugates with cobra venom factor using heterobifunctional cross-linking reagents.
Vogel CW. Vogel CW. Targeted Diagn Ther. 1988;1:191-224. Targeted Diagn Ther. 1988. PMID: 2979056 Review. No abstract available. - Recombinant cobra venom factor.
Vogel CW, Fritzinger DC, Hew BE, Thorne M, Bammert H. Vogel CW, et al. Mol Immunol. 2004 Jun;41(2-3):191-9. doi: 10.1016/j.molimm.2004.03.011. Mol Immunol. 2004. PMID: 15159065 Review.
Cited by
- Solution structure of CCP modules 10-12 illuminates functional architecture of the complement regulator, factor H.
Makou E, Mertens HD, Maciejewski M, Soares DC, Matis I, Schmidt CQ, Herbert AP, Svergun DI, Barlow PN. Makou E, et al. J Mol Biol. 2012 Dec 14;424(5):295-312. doi: 10.1016/j.jmb.2012.09.013. Epub 2012 Sep 25. J Mol Biol. 2012. PMID: 23017427 Free PMC article. - [The relevance of the inflammatory response in the injured brain].
Schmidt OI, Leinhase I, Hasenboehler E, Morgan SJ, Stahel PF. Schmidt OI, et al. Orthopade. 2007 Mar;36(3):248, 250-8. doi: 10.1007/s00132-007-1061-z. Orthopade. 2007. PMID: 17333066 Review. German. - Complement-targeted therapeutics.
Ricklin D, Lambris JD. Ricklin D, et al. Nat Biotechnol. 2007 Nov;25(11):1265-75. doi: 10.1038/nbt1342. Nat Biotechnol. 2007. PMID: 17989689 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous