Discovery and structure–activity relationships of small molecules that block the human immunoglobulin G–human neonatal Fc receptor (hIgG–hFcRn) protein–protein interaction |
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Authors: | Zhaolin Wang Cara Fraley Adam R Mezo |
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Institution: | Biogen Idec Hemophilia, 9 Fourth Avenue, Waltham, MA 02451, USA |
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Abstract: | The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease. Small molecules that block the protein–protein interactions of human IgG–human FcRn may lower pathogenic autoantibodies and provide effective treatment. A novel class of quinoxalines has been discovered as antagonists of the IgG:FcRn protein–protein interaction through optimization of a hit derived from a virtual ligand-based screen. |
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