Compstatin: A Complement Inhibitor on its Way to Clinical Application

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 632)


Therapeutic modulation of the human complement system is considered a promising approach for treating a number of pathological conditions. Owing to its central position in the cascade, component C3 is a particularly attractive target for complement-specific drugs. Compstatin, a cyclic tridecapeptide, which was originally discovered from phage-display libraries, is a highly potent and selective C3 inhibitor that demonstrated clinical potential in a series of experimental models. A combination of chemical, biophysical, and computational approaches allowed a remarkable optimization of its binding affinity towards C3 and its inhibitory potency. With the recent announcement of clinical trials with a compstatin analog for the treatment of age-related macular degeneration, another important milestone has been reached on its way to a drug. Furthermore, the release of a co-crystal structure of compstatin with C3c allows a detailed insight into the binding mode and paves the way to the rational design of peptides and mimetics with improved activity. Considering the new incentives and the promising pre-clinical results, compstatin seems to be well equipped for the challenges on its way to a clinical therapeutic.


Complement Activation Paroxysmal Nocturnal Hemoglobinuria Membrane Attack Complex Hereditary Angioedema Complement Inhibition 



This work was supported by the National Institutes of Health grants GM062134, GM069736, EB003968, and AI068730.


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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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