title: Development of small molecules to target the IgE:FcεRI protein-protein interaction in allergies.
abstract: The protein-protein interaction (PPI) between IgE and its high-affinity receptor (FcεRI) is a key component of the allergic response. Inhibiting the IgE:FcεRI PPI is an attractive strategy for therapeutic intervention and the development of allergy treatments. This PPI has been validated as a viable target by the monoclonal anti-IgE antibody omalizumab (Xolair(®)), which has demonstrated clinical efficacy when prescribed to treat moderate-to-severe asthma and hay fever, but small molecules would be a more convenient form of treatment. Cyclic peptides, small proteins and a natural product have all been developed to target the IgE:FcεRI PPI, and these will be discussed in this review. Targeting the IgE:FcεRI complex with small molecules presents various challenges, some of which are inherent in all PPI targets but some of which are unique to this system, which presents great opportunities for the development of new therapeutics for the treatment of allergies.
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. lucy.smith05@imperial.ac.uk
authors.forename: Lucy D
authors.initials: LD
authors.lastname: Smith
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
authors.forename: Alan C
authors.initials: AC
authors.lastname: Spivey
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy; D001665:Binding Sites / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000737:chemistry / Q000378:metabolism; D000069444:Omalizumab; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D010456:Peptides, Cyclic; D017455:Receptors, IgE; D054852:Small Molecule Libraries; D000069444:Omalizumab; D007073:Immunoglobulin E