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    Curr Opin Investig Drugs. 2004 Nov;5(11):1164-73.

    Synthetic small-molecule complement inhibitors.

    Holland MC, Morikis D, Lambris JD.

    Source

    University of Pennsylvania, Protein Chemistry Laboratory, Department of Pathology and Laboratory Medicine, 402 Stellar Chance, 422 Curie Blvd, Philadelphia, PA 19104, USA.

    Abstract

    During the past few years, several large molecular-weight compounds with complement-inhibitory activities have entered clinical trials for a wide variety of acute and chronic inflammatory conditions. Various small synthetic compounds that offer several advantages over the larger complement inhibitors are also being discovered at a rapid pace. In this review, the focus will be on three of these small molecules, a C3-binding peptide, compstatin; a synthetic peptidic antagonist of the C5a anaphylatoxin receptor, 3D53; and a non-peptidergic antagonist of the C3a anaphylatoxin receptor, SB-290157. In recent years, compstatin has undergone a series of optimizations that have led to more active and stable analogs, while 3D53 and SB-290157 have been more extensively tested in animal models of various human inflammatory diseases. These compounds have been shown to be effective and display little or no toxicity, and as such may be promising new candidates for further therapeutic development.

    PMID:
    15573867
    [PubMed - indexed for MEDLINE]

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