Identification of a new class of small molecule C5a receptor antagonists
| Autor: | John W. Ellingboe, Pawel Nowak, Kimberly Crouse, Derek C. Cole, Jack J. Chen, Wei Li, Gabriel Berstein, Gregory J. Tawa, Greg Ciszewski |
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| Rok vydání: | 2009 |
| Předmět: |
Neutrophils
Clinical Biochemistry Molecular Conformation Pharmaceutical Science chemical and pharmacologic phenomena Pharmacology Biochemistry C5a receptor Cell Line Mice Drug Discovery Calcium flux Animals Humans Anaphylatoxin Receptor Molecular Biology Receptor Anaphylatoxin C5a G protein-coupled receptor Sulfonamides Chemistry Organic Chemistry hemic and immune systems Biological activity respiratory system Complement system High-Throughput Screening Assays Cell culture Molecular Medicine Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(2) |
| ISSN: | 1464-3405 |
| Popis: | C5a is a terminal product of the complement cascade that activates and attracts inflammatory cells including granulocytes, mast cells and macrophages via a specific GPCR, the C5a receptor (C5aR). Inhibition of C5a/C5aR interaction has been shown to be efficacious in several animal models of autoimmune diseases, including RA, SLE and asthma. This account reports the discovery of a new class of C5aR antagonists through high-throughput screening. The lead compounds in this series are selective and block C5a binding, C5a-promoted calcium flux in human neutrophils with nanomolar potency. |
| Databáze: | OpenAIRE |
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