title: Discovery and structure-activity relationships of small molecules that block the human immunoglobulin G-human neonatal Fc receptor (hIgG-hFcRn) protein-protein interaction.
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.
authors: Biogen Idec Hemophilia, 9 Fourth Avenue, Waltham, MA 02451, USA.
authors: Zhaolin
authors: Z
authors: Wang
authors: Cara
authors: C
authors: Fraley
authors: Adam R
authors: AR
authors: Mezo
mesh_terms: D004353:Drug Evaluation, Preclinical; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D011961:Receptors, Fc / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D011810:Quinoxalines; D011961:Receptors, Fc; C100688:Fc receptor, neonatal