Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy
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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
Jack W. Singer, email: [email protected]
Keywords: interleukin-1 receptor associated kinase (IRAK1); inflammatory diseases; cancer; MyD88; pacritinib
Received: July 15, 2018 Accepted: August 15, 2018 Published: September 07, 2018
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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