title: Back to the future: oral targeted therapy for RA and other autoimmune diseases.
abstract: The molecular biology revolution coupled with the development of monoclonal antibody technology enabled remarkable progress in rheumatology therapy, comprising an array of highly effective biologic agents. With advances in understanding of the molecular nature of immune cell receptors came elucidation of intracellular signalling pathways downstream of these receptors. These discoveries raise the question of whether selective targeting of key intracellular factors with small molecules would add to the rheumatologic armamentarium. In this Review, we discuss several examples of this therapeutic strategy that seem to be successful, and consider their implications for the future of immune-targeted treatments. We focus on kinase inhibitors, primarily those targeting Janus kinase family members and spleen tyrosine kinase, given their advanced status in clinical development and application. We also summarize other targets involved in signalling pathways that might offer promise for therapeutic intervention in the future.
authors: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Department of Health and Human Services, Building 10, Rm 13C103C, 10 Center Drive, Bethesda, MD 20892-1930, USA. osheajo@mail.nih.gov
authors: John J
authors: JJ
authors: O'Shea
authors: Arian
authors: A
authors: Laurence
authors: Iain B
authors: IB
authors: McInnes
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D053613:Janus Kinase 1 / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018121:Receptors, Cytokine / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology; D000072377:Syk Kinase; D013844:Thiazoles
chemical_list: D018501:Antirheumatic Agents; D047908:Intracellular Signaling Peptides and Proteins; D018121:Receptors, Cytokine; D013844:Thiazoles; C004474:nithiamide; D011505:Protein-Tyrosine Kinases; D053613:Janus Kinase 1; C000606896:SYK protein, human; D000072377:Syk Kinase