The Therapeutic Potential for PI3K Inhibitors in Autoimmune Rheumatic Diseases

Banham-Hall, Edward; Clatworthy, Menna R; Okkenhaug, Klaus

The Therapeutic Potential for PI3K Inhibitors in Autoimmune Rheumatic Diseases

Edward Banham-Hall¹, Menna R Clatworthy², Klaus Okkenhaug^{*, 1}

¹ Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, CB22 3AT, UK

² Cambridge Institute for Medical Research and the Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0XY, UK

Article Information

Identifiers and Pagination:

Year: 2012
Volume: 6
Issue: Suppl 2
First Page: 245
Last Page: 258
Publisher ID: TORJ-6-245
DOI: 10.2174/1874312901206010245

Article History:

Received Date: 14/7/2011
Revision Received Date: 16/11/2011
Acceptance Date: 20/11/2011
Electronic publication date: 7/9/2012
Collection year: 2012

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© Banham-Hall et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

^* Address correspondence to this author at the Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, CB22 3AT, UK; Tel: (01223) 496000; Fax: (01223) 496002; E-mail: klaus.okkenhaug@babraham.ac.uk

The class 1 PI3Ks are lipid kinases with key roles in cell surface receptor-triggered signal transduction pathways. Two isoforms of the catalytic subunits, p110γ and p110δ, are enriched in leucocytes in which they promote activation, cellular growth, proliferation, differentiation and survival through the generation of the second messenger PIP3. Genetic inactivation or pharmaceutical inhibition of these PI3K isoforms in mice result in impaired immune responses and reduced susceptibility to autoimmune and inflammatory conditions. We review the PI3K signal transduction pathways and the effects of inhibition of p110γ and/or p110δ on innate and adaptive immunity. Focusing on rheumatoid arthritis and systemic lupus erythematosus we discuss the preclinical evidence and prospects for small molecule inhibitors of p110γ and/or p110δ in autoimmune disease.

Keywords: PI3K inhibitors, humoral immune, systemic lupus erythematosus, pleckstrin homology, autoimmunity, rheumatoid arthritis, PI3K..

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Xiaodong Zhou

Department of Internal Medicine
University of Texas
Houston, TX
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The Open Rheumatology Journal
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RESEARCH ARTICLE

The Therapeutic Potential for PI3K Inhibitors in Autoimmune Rheumatic Diseases

Article Information

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Abstract

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About the Editor

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The Open Rheumatology Journal

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