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: Zhaolin Wang, Cara Fraley, Adam R Mezo
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 5 Pg. 1253-6 (Mar 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23375228 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Histocompatibility Antigens Class I
• Immunoglobulin G
• Ligands
• Quinoxalines
• Receptors, Fc
• Fc receptor, neonatal

Topics

• Drug Evaluation, Preclinical
• Histocompatibility Antigens Class I (immunology, metabolism)
• Humans
• Immunoglobulin G (immunology, metabolism)
• Ligands
• Protein Interaction Domains and Motifs (drug effects)
• Quinoxalines (pharmacology)
• Receptors, Fc (antagonists & inhibitors, immunology, metabolism)
• Structure-Activity Relationship