title: Protein kinase inhibitors in the treatment of inflammatory and autoimmune diseases.
abstract: Protein kinases mediate protein phosphorylation, which is a fundamental component of cell signalling, with crucial roles in most signal transduction cascades: from controlling cell growth and proliferation to the initiation and regulation of immunological responses. Aberrant kinase activity is implicated in an increasing number of diseases, with more than 400 human diseases now linked either directly or indirectly to protein kinases. Protein kinases are therefore regarded as highly important drug targets, and are the subject of intensive research activity. The success of small molecule kinase inhibitors in the treatment of cancer, coupled with a greater understanding of inflammatory signalling cascades, has led to kinase inhibitors taking centre stage in the pursuit for new anti-inflammatory agents for the treatment of immune-mediated diseases. Herein we discuss the main classes of kinase inhibitors; namely Janus kinase (JAK), mitogen-activated protein kinase (MAPK) and spleen tyrosine kinase (Syk) inhibitors. We provide a mechanistic insight into how these inhibitors interfere with kinase signalling pathways and discuss the clinical successes and failures in the implementation of kinase-directed therapeutics in the context of inflammatory and autoimmune disorders.
authors: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors: H
authors: H
authors: Patterson
authors: R
authors: R
authors: Nibbs
authors: I
authors: I
authors: McInnes
authors: S
authors: S
authors: Siebert
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000072377:Syk Kinase; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: autoimmunity; novel biological therapies; protein kinases; signalling/signal transduction