Oncotarget

Reviews:

Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy

Jack W. Singer _, Angela Fleischman, Suliman Al-Fayoumi, John O. Mascarenhas, Qiang Yu and Anupriya Agarwal

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Oncotarget. 2018; 9:33416-33439. https://doi.org/10.18632/oncotarget.26058

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Abstract

Jack W. Singer1, Angela Fleischman2, Suliman Al-Fayoumi1, John O. Mascarenhas3, Qiang Yu4 and Anupriya Agarwal5

1CTI Biopharma Corporation, Seattle, WA, USA

2Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA

3Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

4Genome Institute of Singapore, Singapore, SG, Singapore

5Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

Correspondence to:

Jack W. Singer, email: jsinger@ctibiopharma.com

Keywords: interleukin-1 receptor associated kinase (IRAK1); inflammatory diseases; cancer; MyD88; pacritinib

Received: July 15, 2018     Accepted: August 15, 2018     Published: September 07, 2018

ABSTRACT

Interleukin-1 receptor-associated kinases (IRAK1, IRAK2, IRAK3 [IRAK-M], and IRAK4) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways, through which they regulate innate immunity and inflammation. Evidence exists that IRAKs play key roles in the pathophysiologies of cancers, and metabolic and inflammatory diseases, and that IRAK inhibition has potential therapeutic benefits. Molecules capable of selectively interfering with IRAK function and expression have been reported, paving the way for the clinical evaluation of IRAK inhibition. Herein, we focus on IRAK1, review its structure and physiological roles, and summarize emerging data for IRAK1 inhibitors in preclinical and clinical studies.


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